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Kikuchi M.,Keio University | Nagata H.,Keiyu Hospital | Watanabe N.,Tokai University | Watanabe H.,Hiroshima University | And 2 more authors.
BMC Gastroenterology | Year: 2010

Background: Doublecortin and calcium/calmodulin-dependent protein kinase-like-1 (DCAMKL1) is a candidate marker for progenitor cells in the gastrointestinal mucosa. Lineage cells in the gastric mucosa are derived from progenitor cells, but this process can be altered after injury. Therefore, we explored DCAMKL1 expression under pathological conditions.Methods: An immunohistochemical analysis was performed in rat stomach with acute superficial injury, chronic ulcer, intestinal metaplasia and dysplasia.Results: DCAMKL1 was exclusively expressed in immature quiescent cells in the isthmus of normal fundic glands, where putative progenitor cells are thought to reside. DCAMKL1-positive cells and proliferating cells shed into the lumen after superficial injury and re-appeared during the regenerative process, mainly in the superficial mucosa. In the marginal mucosa around the active ulcer, parietal and chief cells diminished, foveolar hyperplasia was evident, and trefoil factor family 2 (TFF2)/spasmolytic polypeptide-expressing metaplasia (SPEM) emerged at the gland base. DCAMKL1 cells re-emerged in the deep mucosa juxtaposed with SPEM and proliferating cells. In the healing ulcer, the TFF2 cell population expanded and seemed to redifferentiate to chief cells, while proliferating cells and DCAMKL1 cells appeared above and below the TFF2 cells to promote healing. SPEM appeared and PCNA cells increased in the intestinalized mucosa, and DCAMKL1 was expressed in the proximity of the PCNA cells in the deep mucosa. DCAMKL1, PCNA and TFF2 were expressed in different dysplastic cells lining dilated glands near SPEM.Conclusion: The ultrastructural appearance of DCAMKL1-positive cells and the expression patterns of DCAMKL1 in normal and pathological states indicate that the cells belong to a progenitor cell population. DCAMKL1 expression is closely associated with TFF2/SPEM cells after injury. DCAMKL1 cells repopulate close to proliferating, hyperplastic, metaplastic and dysplastic cells, and the progenitor zone shifts according to the pathological circumstances. © 2010 Kikuchi et al; licensee BioMed Central Ltd.

Sugaya N.,Keiyu Hospital | Shinjoh M.,Keio University | Mitamura K.,Eiju General Hospital | Takahashi T.,Keio University
Journal of Infection | Year: 2011

Objective: There were many cases of pandemic influenza A (H1N1) 2009 (H1N1/09) in Japan during the 2009-2010 epidemic. They accounted for 16% of the total population (20.7 million/128 million), and 59% of the patients were children 15 years of age and under (12.2 million/20.7million). However, there were only 38 paediatric deaths. We analyzed the clinical manifestations and treatment of children hospitalized because of H1N1/09 infection in order to clarify the association between treatment with neuraminidase inhibitors and the low mortality rate. Methods: A retrospective chart review was performed on a total of 1000 paediatric inpatients. Results: The causes of the hospitalizations were respiratory complications in 651 cases (65.1%), neurological complications in 255 cases (25.5%) and other complications in 94 cases. Neuraminidase inhibitors, primarily oseltamivir, had been used to treat 984 (98.4%) of the 1000 patients, and in 88.9% of the patients, treatment with neuraminidase inhibitors was initiated within 48 h after the onset of illness. Only 12 (1.2%) of the 1000 patients underwent mechanical ventilation, and one patient died of H1N1/09 infection. Conclusions: Although a high proportion of the patients in this study had severe respiratory complications, the case fatality rate was only 0.1%. The low mortality rate of children due to the H1N1/09 epidemic in Japan was probably attributable to the universal implementation of early treatment with neuraminidase inhibitors. © 2011 The British Infection Association.

Sugaya N.,Keiyu Hospital
Journal of Infection and Chemotherapy | Year: 2011

Almost all patients with an influenza-like illness in Japan are now tested with rapid diagnostic tests, and when positive, they are treated with a neuraminidase inhibitor (NAI). Japan may have had the lowest case fatality rate for symptomatic illness (\0.001%, 198/20.7 million) in the H1N1/09 pandemic because of the universal implementation of early treatment with NAI. A study of 1,000 children hospitalized because of a H1N1/09 infection revealed that NAIs, primarily oseltamivir, had been used to treat 984 (98.4%) of the 1,000 patients. In 88.9% of the patients, treatment with NAIs was initiated within 48 h after the onset of illness. In addition to oseltamivir and zanamivir, the newly approved inhalant drug, laninamivir, and the newly approved intravenous drug, peramivir, were used in Japan during the 2010-2011 season. Neuropsychiatric disorders that were suspected of being adverse reactions to oseltamivir became a cause of concern in 2007. The Health, Labour and Welfare Ministry issued an emergency instruction to suspend the use of oseltamivir to treat patients between the ages of 10 and 19 years. However, according to the Vital Statistics data, the widespread use of oseltamivir has not caused an increase in deaths as a result of accidental falls or intentional jumps from buildings. Although oseltamivir is widely used in Japan, no outbreaks have been caused by oseltamivir-resistant viruses, and no serious illness caused by oseltamivir-resistant viruses has ever been reported. © Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases 2011.

Shinjoh M.,Keio University | Takano Y.,Keio University | Takahashi T.,Keio University | Hasegawa N.,Keio University | And 2 more authors.
Pediatric Infectious Disease Journal | Year: 2012

BACKGROUND: Postexposure prophylaxis (PEP) using neuraminidase inhibitors against exposure to influenza virus has been well studied in household settings but not in nosocomial settings in pediatric wards. METHODS: We used oseltamivir or zanamivir as PEP in our pediatric wards. All influenza cases were diagnosed by the influenza rapid diagnostic test. RESULTS: Between 2003 and 2011, there were 20 nosocomial introductions of influenza (10 were A, 9 were B and 1 was undetermined). The index cases consisted of 17 inpatients, 2 parents and 1 medical staff member. The 17 inpatients had been admitted to the hospital for reasons other than infectious disease and they developed influenza after hospitalization. Among the 81 contacts, 28 (35%) were exposed to influenza A, and 52 (64%) were exposed to influenza B. The rate of secondary infection among contacts not given PEP was 29% (5/17), and the rate among contacts given PEP was significantly lower, 3% (2/63; P = 0.004). The 2 infected contacts who had been given PEP were both influenza B cases, and both had received oseltamivir. The contacts who received PEP within 24 hours (59), for influenza A (23) and those who received zanamivir (15) did not develop influenza. No adverse events were reported. CONCLUSIONS: PEP using oseltamivir or zanamivir for unexpected occurrences of nosocomial influenza in pediatric wards is safe and effective. The influenza rapid diagnostic test that we used was helpful for detecting nosocomial influenza in children. Copyright © 2012 by Lippincott Williams & Wilkins.

Hikata T.,Keiyu Hospital | Kamata M.,Keiyu Hospital | Furukawa M.,Keiyu Hospital
Journal of Spinal Disorders and Techniques | Year: 2014

STUDY DESIGN: A retrospective study. SUMMARY OF BACKGROUND DATA: Posterior lumbar interbody fusion (PLIF) increases mechanical stress and can cause degenerative changes at the adjacent segment. However, the precise causes of adjacent segment disease (ASD) after PLIF are not known, and it is unclear whether simultaneous decompression surgery for symptomatic ASD is effective. OBJECTIVE: To study, radiographically and symptomatically, the risk factors for adjacent segment disease (ASD) in the lumbar spine after L4/5 PLIF and to examine whether decompression surgery for the adjacent segment (L3/4) reduces the occurrence of symptomatic ASD. METHODS: Fifty-four patients who underwent L4/5 PLIF for L4 degenerative spondylolisthesis and could be followed up for at least 2 years were included. Of these, 37 were treated simultaneously with decompression surgery at L3/4. We measured radiographic changes and assessed symptoms from the cranial adjacent segment. RESULTS: Thirty-one patients (57.4%) met radiologic criteria for ASD. The length of follow-up (P=0.004) and simultaneous decompression surgery at L3/4 (P=0.009) were statistically significant factors for radiologic diagnosis of ASD. Seven patients (13.0%) had symptomatic ASD: 6 in the decompression group (16.2%) and 1 in the PLIF-only group (5.9%). Simultaneous decompression surgery did not reduce the incidence of symptomatic ASD (P=0.256). Local lordosis at the fused segment (P=0.005) and the sagittal angle of the facet joint at L3/4 (P=0.024) were statistically significant predictors of symptomatic ASD, which was accompanied by postoperative anterior listhesis above the fused segment (S group, 8.4%±8.0%; nonsymptomatic group:-0.7%±5.0%, P=0.024). CONCLUSIONS: Patients whose facet joint at the adjacent segment had a more sagittal orientation had postoperative anterior listhesis, which caused symptomatic ASD. Simultaneous decompression surgery without fusion at the adjacent level was not effective for these patients, but rather, there was a possibility that it induced symptomatic ASD. Copyright © 2012 by Lippincott Williams &Wilkins.

In the past, Japan's strategy for controlling influenza was to vaccinate schoolchildren based on the theory that this could reduce influenza epidemics in the community, and a special program to vaccinate schoolchildren against influenza was begun in 1962. However, the program was discontinued in 1994 because of lack of evidence that it had limited the spread of influenza in the community. In 2001, it was reported that a clear decrease in excess mortality had coincided with the timing of the schoolchild vaccination program. This decrease could have potentially occurred because elderly people were protected by herd immunity generated by the program. Moreover, the program protected the younger siblings of schoolchildren against influenza-associated encephalopathy. Finally, the program was effective in reducing the number of class cancellations and absenteeism from school. During the period when the program was in effect, Japanese schoolchildren served as a barrier against influenza in the community. © 2014 Informa UK Ltd.

Nakamura Y.,Keiyu Hospital
Asian journal of endoscopic surgery | Year: 2012

Hepatic hydrothorax is defined as the presence of a significant pleural effusion that develops in a patient with cirrhosis of the liver who does not have an underlying cardiac or pulmonary disease. There have been few published case reports dealing with hepatic hydrothorax treated surgically. Recently, we treated a patient with refractory hepatic hydrothorax by directly suturing the diaphragmatic defect during VATS. During surgery, the diaphragmatic defect was identified by using abdominal insufflation with CO(2) . The defect was sutured and the diaphragm was covered by polyglycolic acid felt and fibrin glue. After surgery, the patient's pleural effusion improved, his postoperative course was uneventful and he did not require a drainage tube at discharge. © 2012 Japan Society for Endoscopic Surgery, Asia Endosurgery Task Force and Blackwell Publishing Asia Pty Ltd.

Sugaya N.,Keiyu Hospital | Ohashi Y.,University of Tokyo
Antimicrobial Agents and Chemotherapy | Year: 2010

We conducted a double-blind, randomized controlled trial to compare a long-acting neuraminidase inhibitor, laninamivir octanoate, with oseltamivir. Eligible patients were children 9 years of age and under who had febrile influenza symptoms of no more than 36-h duration. Patients were randomized to 1 of 3 treatment groups: a group given 40 mg laninamivir (40-mg group), a group given 20 mg laninamivir (20-mg group), and an oseltamivir group. Laninamivir octanoate was administered as a single inhalation. Oseltamivir (2 mg/kg of body weight) was administered orally twice daily for 5 days. The primary end point was the time to alleviation of influenza illness. The primary analysis included 184 patients (61, 61, and 62 in the 40-mg group, 20-mg group, and oseltamivir group, respectively). Laninamivir octanoate markedly reduced the median time to illness alleviation in comparison with oseltamivir in patients infected with oseltamivir-resistant influenza A (H1N1) virus, and the reductions were 60.9 h for the 40-mg group and 66.2 h for the 20-mg group. On the other hand, there were no significant differences in the times to alleviation of illness between the laninamivir groups and oseltamivir group for patients with influenza A (H3N2) or B virus infection. Laninamivir octanoate was well tolerated. The most common adverse events were gastrointestinal events. Laninamivir octanoate was an effective and well-tolerated treatment for children with oseltamivir-resistant influenza A (H1N1) virus infection. Further study will be needed to confirm clinical efficacy against influenza A (H3N2) or B virus infection. Its ease of administration is noteworthy, because a single inhalation is required during the course of illness. Copyright © 2010, American Society for Microbiology. All Rights Reserved.

Sugaya N.,Keiyu Hospital | Kohno S.,Nagasaki University | Ishibashi T.,Shionogi and Co. | Wajima T.,Shionogi and Co. | Takahashi T.,Keio University
Antimicrobial Agents and Chemotherapy | Year: 2012

Peramivir is a new neuraminidase inhibitor for intravenous administration that was first introduced in clinical practice in Japan. We conducted a multicenter, open-label, uncontrolled study in children with influenza virus infection ranging in age from ≥28 days to < 16 years during the 2009 pandemic A (H1N1) influenza epidemic to evaluate the efficacy, safety, and pharmacokinetics of peramivir in children after intravenous infusion of 10 mg/kg (600 mg maximum) once daily. Among the 106 children (125 days to 15 years old) confirmed to have been infected with the pH1N1 virus by the PCR who were treated with peramivir, the median time to alleviation of symptoms was 29.1 h (95% confidence interval = 22.1 to 32.4), and the proportion of the 106 children who were virus positive was 78.2% on day 2 after the start of treatment and had decreased to 7.1% on day 6. The results of the safety evaluation among 117 patients enrolled in this study showed that adverse events and adverse drug reactions were reported in 62.4 and 29.1%, respectively, of the patients. All of the adverse events and adverse drug reactions resolved or improved rapidly. A population pharmacokinetic analysis was performed on the basis of 297 observed plasma concentration data obtained from 115 children with influenza virus infection. Peramivir exposure in children was within the range of levels within which the efficacy and safety was confirmed in adults, and it is considered that peramivir is clinically and virologically effective and safe in children with pH1N1 virus infection. Copyright © 2012, American Society for Microbiology. All Rights Reserved.

Immunoglobulin G4-related disease (IgG4-RD) is a novel clinical disease entity characterized by elevated serum IgG4 concentration and tumefaction or tissue infiltration by IgG4-positive plasma cells. IgG4-RD can occur in various organs, including the pancreas, lacrimal gland, salivary gland, thyroid, lung, bile duct, liver, gastrointestinal tract, kidney, prostate, retroperitoneum, arteries, lymph nodes, skin, and breast. Steroid therapy is often effective. In the field of neurology, pachymeningitis (IgG4-related pachymeningitis) and hypophysitis (IgG4-related hypophysitis) are known to be related to IgG4-RD. Recently, a few papers have described the involvement of peripheral nerves in IgG4-RD. Here, we describe the concept of IgG4-RD and highlight the involvement of the central and peripheral nervous systems in IgG4-RD.

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