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PubMed | Chutoen General Medical Center, Toshiba Corporation, Kuwana West Medical Center, Nagoya City University and 4 more.
Type: Journal Article | Journal: Liver international : official journal of the International Association for the Study of the Liver | Year: 2016

Hepatitis E virus (HEV) genotype 4 has mainly been isolated from sporadic hepatitis cases and swine in Asian countries. We analysed the origin and global dispersal history of genotype 4 using a Bayesian phylogeographical approach.The 412-nucleotide sequences of open reading frame 2 of genotype 4 (47 Japanese, 40 Chinese, 1 Indian, 8 Indonesian, 1 Korean, 1 Taiwanese, 2 Danish and 2 Italian), of which sampling date and location were known, were collected. Evolutionary rate, divergence time, demographic growth and phylogeography were co-estimated in the Bayesian statistical inference framework implemented in the BEAST package to model spatial dispersal on a time-scaled genealogy.The most probable origin of genotype 4 was Japan and the time of origin was 1909 (95% highest posterior density, 1871-1940). Seven lineages of genotype 4 migrated from Japan to China. The analysis also showed the migration of genotype 4 from Japan or China to India and Indonesia and from China to Indonesia, Taiwan, Korea and a few European countries.Swine trade between countries coincided with the migration time and direction of genotype 4 in some cases and was considered the primary cause of dispersal. However, there was no clear cause of dispersal for some cases, for which no records of pig trade were found. Future research should analyse additional nucleotide sequences paired with epidemiological data from various countries to improve our understanding of HEV dispersal.


PubMed | Hamamatsu University School of Medicine, Chutoen General Medical Center, Suzukake Central Hospital, Nagasaki Harbor Medical Center City Hospital and 11 more.
Type: Journal Article | Journal: The Journal of urology | Year: 2015

The optimal dose of intravesical bacillus Calmette-Gurin for the treatment of nonmuscle invasive bladder cancer is controversial. We investigated if induction therapy with low dose bacillus Calmette-Gurin could achieve a complete response rate similar to that of standard dose bacillus Calmette-Gurin, with less toxicity and higher quality of life.After transurethral resection, patients with unresectable multiple nonmuscle invasive bladder cancer and/or carcinoma in situ were randomized to receive standard (80 mg) or low dose (40 mg) bacillus Calmette-Gurin instillation induction therapy (weekly, 8 times). The primary end point was noninferiority of low dose bacillus Calmette-Gurin with a null hypothesis of a 15% decrease in complete response rate. Secondary end points were recurrence-free survival, progression-free survival, overall survival, patient compliance, adverse events and quality of life using the EORTC QLQ-C30.In an intent to treat analysis of 166 patients the complete response rates for low dose and standard dose bacillus Calmette-Gurin were 79% (95% CI 0.70-0.88) and 85% (95% CI 0.77-0.92), respectively. Dunnett-Gent analysis revealed that the null hypothesis of inferiority of low dose bacillus Calmette-Gurin in terms of complete response could not be rejected (p = 0.119). However, there were no significant differences between the groups in terms of recurrence, progression and overall survival. Low dose bacillus Calmette-Gurin was associated with significantly less fever (p = 0.001) and micturition pain (p = 0.047), and significantly higher quality of life scores for global quality of life, role functioning and functional impairment.The noninferiority of low dose bacillus Calmette-Gurin was not proven. However, low dose bacillus Calmette-Gurin was associated with lower toxicity and higher quality of life compared to standard dose bacillus Calmette-Gurin in patients with nonmuscle invasive bladder cancer.


PubMed | Asahi University, Gifu University, Tokyo Metropolitan University, Tokyo Electron and Chutoen General Medical Center
Type: Journal Article | Journal: Urologic oncology | Year: 2015

Docetaxel is used as the first-line chemotherapy for castration-resistant prostate cancer (CRPC), but docetaxel resistance occurs in part owing to induction of P-glycoprotein (P-gp) encoded by multidrug resistance protein 1 (MDR1) gene. A recently developed taxane-cabazitaxel-has poor affinity for P-gp and is thereby effective in docetaxel-resistant CRPC. It has been recently demonstrated that exosomes in the body fluids could serve as a diagnostic marker because they contain proteins and RNAs specific to the cells from which they are derived. In this study, we aimed to investigate if P-gp in blood exosomes could be a marker to diagnose docetaxel resistance and select a taxoid for patients with CRPC.Exosomes were isolated by differential centrifugation from docetaxel-resistant prostate cancer (PC-3) cells (PC-3R) and their parental PC-3 cells and from the serum of patients. Silencing of P-gp was performed by small interfering RNA transfection. Protein expression was examined by Western blot analysis. Viability of cells treated with docetaxel or cabazitaxel was determined by water soluble tetrazolium salt (WST) assay.The level of P-gp was higher in exosomes as well as cell lysates from PC-3R cells than in those from PC-3 cells. Cabazitaxel effectively killed PC-3R cells, and MDR1 knockdown improved the sensitivity of PC-3R cells to docetaxel but not to cabazitaxel. The P-gp level in blood exosomes was relatively higher in clinically docetaxel-resistant patients than in therapy-nave patients.Our results suggest that detection of P-gp in blood exosomes, which is involved in resistance to docetaxel but not to cabazitaxel, could be useful to diagnose docetaxel resistance and select an appropriate taxoid for patients with CRPC-docetaxel or cabazitaxel.


PubMed | Hamamatsu University School of Medicine, Chutoen General Medical Center, General Electric and Hamamatsu University
Type: Journal Article | Journal: Journal of magnetic resonance imaging : JMRI | Year: 2016

1) To assess the usefulness of an elastic belt bracing the upper abdomen for reducing the miscalculated areas of the pancreas on 3.0T magnetic resonance elastography (MRE); 2) to test whether MRE can detect difference of stiffness between normal pancreas and the focal pancreatic diseases.Using an initial eight normal volunteers, miscalculated areas were compared between MRE with the elastic belt and without the belt on 3.0T MRI. Then, using the belt, MRE of the normal pancreas was measured using 14 volunteers and 11 patients with focal pancreatic lesions.The median (95% confidence interval [CI]) percentages of correctly calculated areas were 57.4% (32.9-63.0) with the elastic belt and 35.3% (11.4-60.4) without the belt (P=0.0078). The stiffness of each pancreatic segment of the normal volunteers (meanSE) was 2.370.16 kPa for the head, 2.460.17 kPa for the body, and 2.580.26 kPa for the tail. The stiffness of seven pancreatic cancers was 6.060.49 kPa, which was higher than the overall pancreatic stiffness of the normal volunteers (2.470.11 kPa, P<0.0001). Stiffness of the pancreatic lesions in the head of 6.030.42 kPa, body of 5.570.82 kPa, and tail of 5.91.9 kPa were also higher than those of corresponding segments of the normal volunteers (P=0.0011, 0.0029, and 0.029, respectively).With the elastic belt, miscalculation of the pancreatic stiffness was reduced. MRE showed differences of stiffness between normal pancreas and pancreatic lesions.


Kanbara S.,Chutoen General Medical Center | Yukawa Y.,Chubu Rosai Hospital | Ito K.,Chubu Rosai Hospital | Machino M.,Chubu Rosai Hospital | Kato F.,Chubu Rosai Hospital
European Spine Journal | Year: 2014

Purpose: Some reported studies have evaluated the dural sac in patients with lumbar spinal stenosis (LSS) by computed tomography (CT) after conventional myelography or magnetic resonance imaging (MRI). But they have been only able to evaluate static factors. No reports have described detailed dynamic changes in the dural sac during flexion and extension observed by multidetector-row computed tomography (MDCT). The aim of this study was to elucidate or demonstrate, in detail, the influence of dynamic factors on the severity of stenosis. Methods: One hundred patients with LSS were enrolled in this study. All underwent MDCT in both flexion and extension positions after myelography, in addition to undergoing MRI. The anteroposterior diameter (AP-distance) and cross-sectional area of the dural sac (D-area) were measured at each disc level between L1-2 and L5- S1. The dynamic change in the D-area was defined as the absolute value of the difference between flexion and extension. The rate of dynamic change (dynamic change in D-area/D-area at flexion) in the dural sac at each disc level was also calculated. Results: The average AP-distance in flexion/extension (mm) was 9.2/7.4 at L3-4 and 8.3/7.4 at L4-5. The average D-area in flexion/extension (mm2) was 96.3/73.6 at L3-4 and 72.3/61.0 at L4-5. The values were significantly lower in extension than in flexion at all disc levels from L1-2 to L5-S1. AP-distance was narrowest and D-area smallest at L4-5 during extension. The rates of dynamic changes at L2-3 and L3-4 were higher than those at L4-5. Conclusions: MDCT clearly elucidated the dynamic changes in the lumbar dural sac. Before surgery, MDCT after myelography should be used to evaluate the dynamic change during flexion and extension, especially at L2-3, L3-4, and L4-5. © Springer-Verlag 2013.


Nakamura T.,Nagoya University | Hirayama M.,Nagoya University | Hara T.,Nagoya University | Hara T.,Chutoen General Medical Center | And 4 more authors.
Parkinsonism and Related Disorders | Year: 2014

Purpose: Cardiac sympathetic denervation is associated with orthostatic hypotension (OH) in Parkinson's disease (PD); however, the physiological role of cardiac sympathetic nerves has yet to be elucidated. To clarify the role of the heart in orthostatic stress, we evaluated whether cardiac sympathetic nerves can alter cardiac activity and systolic blood pressure (BP) in association with elevations or depressions of total peripheral resistance during the head-up tilt test. Methods: Ninety-five PD patients and 17 normal controls were enrolled. Using impedance cardiography, we measured total peripheral resistance, stroke volume, heart rate, and systolic BP during the head-up tilt test. Cardiac denervation was defined as a heart-to-mediastinum ratio <1.7 for cardiac 123I-metaiodobenzylguanidine uptake on delayed images. Results: At 60° tilt, total peripheral resistance decreased from the initial value in 49 PD patients. Among these, 36 patients exhibited cardiac denervation with severe reductions in systolic BP but little change in stroke volume; among these patients 22 had OH. The remaining 13 patients without cardiac denervation exhibited significant increases in stroke volume and well-preserved systolic BP with no OH. On the other hand, 46 patients had elevations in total peripheral resistance and reduced stroke volume, but little change in systolic BP, regardless of the presence or absence of cardiac denervation. Only one of these patients experienced OH. Conclusion: Under orthostatic stress, cardiac sympathetic denervation with failure to increase total peripheral resistance leads to large reductions in systolic BP. However, patients without cardiac denervation exhibited a positive inotropic response against vasodilatation, which may prevent OH. © 2014 Elsevier Ltd.


Kanbara S.,Chutoen General Medical Center | Yukawa Y.,Chubu Rosai Hospital | Ito K.,Chubu Rosai Hospital | Machino M.,Chubu Rosai Hospital | Kato F.,Chubu Rosai Hospital
Journal of Neurosurgery: Spine | Year: 2015

The lumbar spinous process-splitting laminectomy (LSPSL) procedure was developed as an alternative to lumbar laminectomy. In the LSPSL procedure, the spinous process is evenly split longitudinally and then divided at its base from the posterior arch, leaving the bilateral paravertebral muscle attached to the lateral aspects. This procedure allows for better exposure of intraspinal nerve tissues, comparable to that achieved by conventional laminectomy while minimizing damage to posterior supporting structures. In this study, the authors make some modifications to the original LSPSL procedure (modified LSPSL), in which laminoplasty is performed instead of laminectomy. The purpose of this study was to compare postoperative outcomes in modified LSPSL with those in conventional laminectomy (CL) and to evaluate bone unions between the split spinous process and residual laminae following modified LSPSL. Forty-seven patients with lumbar spinal stenosis were enrolled in this study. Twenty-six patients underwent modified LSPSL and 21 patients underwent CL. Intraoperative blood loss and surgical duration were evaluated. The Japanese Orthopaedic Association (JOA) scale scores were used to assess parameters before surgery and 12 months after surgery. The recovery rates were also evaluated. Postoperative paravertebral muscle atrophy was assessed using MRI. Bone union rates between the split spinous process and residual laminae were also examined. The mean surgical time and intraoperative blood loss were 25.7 minutes and 42.4 ml per 1 level in modified LSPSL, respectively, and 22.7 minutes and 29.5 ml in CL, respectively. The recovery rate of the JOA score was 64.2% in modified LSPSL and 68.7% in CL. The degree of paravertebral muscle atrophy was 7.8% in modified LSPSL and 22.2% in CL at 12 months after surgery (p < 0.05). The fusion rates of the spinous process with the arcus vertebrae at 6 and 12 months in modified LSPSL were 56.3% and 81.3%, respectively. The modified LSPSL procedure was less invasive to the paravertebral muscles and could be a laminoplasty; therefore, the modified LSPSL procedure presents an effective alternative to lumbar laminectomy. ©AANS, 2015.


PubMed | Hamamatsu University School of Medicine and Chutoen General Medical Center
Type: | Journal: Human fertility (Cambridge, England) | Year: 2016

Assisted reproductive technology (ART) has become widespread, accounting for 2% of all births worldwide, with a similar proportion in Japan. Our goal was to determine whether ART is associated with an increased risk of congenital heart defect (CHD). The study subjects were 2716 pregnant women (2317 in a spontaneous conception [SC] group and 399 in an assisted conception [AC] group). Of patients in the AC group, 142 were treated with ovulation-inducing agents (OIAs), 56 with artificial insemination by the husband (AIH), 159 with in vitro fertilization (IVF), and 42 with intracytoplasmic sperm injection (ICSI). CHD screening on the fetus or newborn was performed using two-dimensional echocardiography. Severe CHD was defined as requiring surgical treatment, or leading to death within one year. There were 2746 births (one of 31 twins was a still birth), 410 resulted from AC and within this group, 111 cases of CHD were found (AC group, 17 [4.1%]; SC group, 94 [4.0%]). Five cases of severe CHD were found in the AC group and 19 in the SC group, with no significant difference between the groups (p=0.892). In conclusion, there was no evidence of increased CHD risk associated with ART treatment.


PubMed | Chutoen General Medical Center
Type: Journal Article | Journal: Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy | Year: 2016

Bordetella bronchiseptica is a bacterial pathogen usually isolated from animals and rarely causes human infections. There are, however, some reports that B.bronchiseptica causes human respiratory infections in immunocompromised patients or those with underlying respiratory diseases, although there is a lack of treatment guidelines. An 80-year-old woman was admitted to our hospital to treat anti-neutrophil cytoplasmic antibodies-associated vasculitis. On the 16th day after admission, she complained of a productive cough with right pleuritic pain and had low-grade fever. After chest CT scans, we diagnosed pneumonia. Gram stain of her sputum revealed moderate levels of gram-negative coccobacilli, which was later identified as B.bronchiseptica by mass spectrometry. According to the result of minimum inhibitory concentration, we successfully treated the pneumonia with minocycline. This case suggests that B.bronchiseptica pneumonia can be treated by minocycline if the minimum inhibitory concentration is less than 0.25g/mL.


PubMed | Chutoen General Medical Center and Nagoya University
Type: Case Reports | Journal: Asian journal of endoscopic surgery | Year: 2016

Laparoscopic surgery for the treatment of a ruptured visceral artery aneurysm is recognized as a challenging procedure. Here, we describe our experience with laparoscopic surgery to treat a ruptured aneurysm of the right gastric artery. A 72-year-old woman was diagnosed with intra-abdominal hemorrhage caused by a ruptured aneurysm of the right gastric artery. Transcatheter arterial embolization failed because the right gastric artery could not be cannulated. Therefore, we performed laparoscopic surgery. Using laparoscopy, we detected that the bleeding from the aneurysm had ceased; thus, the planned procedure was successful. The operative time and intraoperative blood loss were 100min and 5mL, respectively. The patient was discharged 7days after surgery. Laparoscopic surgery after the failure of transcatheter arterial embolization is a suitable and safe procedure for ruptured visceral artery aneurysms, provided the circulatory dynamics are stable as a result of the temporary cessation of bleeding from the ruptured aneurysm.

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