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Objective: Although lobectomy is the standard surgical procedure for operable non-small cell lung cancer (NSCLC), sublobar resection also has been undertaken for various reasons. The aim of this study was to identify risk factors of locoregional recurrence and poor disease-specific survival in patients with clinical stage IA NSCLC undergoing sublobar resection. Methods: We retrospectively reviewed 328 patients with clinical stage IA NSCLC who underwent segmentectomy or wedge resection. Demographic, clinical, and pathologic factors were analyzed using the log-rank test as univariate analyses, and all factors were entered into a Cox proportional hazards regression model for multivariate analyses to identify independent predictors of locoregional recurrence and poor disease-specific survival. Results: The 5- and 10-year locoregional recurrence-free probabilities were 84.8% and 83.6%, respectively, and the 5- and 10-year disease-specific survivals were 83.6% and 73.6%, respectively. Four independent predictors of locoregional recurrence were identified: wedge resection (hazard ratio [HR], 5.787), microscopic positive surgical margin (HR, 3.888), visceral pleural invasion (HR, 2.272), and lymphatic permeation (HR, 3.824). Independent predictors of poor disease-specific survival were identified as follows: smoking status (Brinkman Index
HR, 1.001), wedge resection (HR, 3.183), microscopic positive surgical margin (HR, 3.211), visceral pleural invasion (HR, 2.553), and lymphatic permeation (HR, 3.223). All 4 predictors of locoregional recurrence also were identified as independent predictors of poor disease-specific survival. Conclusions: Segmentectomy should be the surgical procedure of first choice in patients with clinical stage IA NSCLC who are being considered for sublobar resection. Patients having tumors presenting with no suspicious of pleural involvement would be suitable candidates for sublobar resection. © 2013 by The American Association for Thoracic Surgery.

DOI： 10.1016/j.jtcvs.2013.02.057

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Purpose: This study used magnetic resonance imaging (MRI) to evaluate in vivo preoperative changes in the length of the patellar tendon (LPT) in patients undergoing total knee arthroplasty (TKA). We sought to answer two questions: first, does the LPT change with flexion? Second, does the LPT show a gender-specific pattern? Methods: Eighty-five knees in 76 consecutive osteoarthritic patients were evaluated. The age range was 56-90 years (mean 70). The study included 62 females and 14 males. MRI was performed at full extension and at 30, 60, 90, and full flexion. Results: There were significantly different patterns between genders (p &lt
0.001). The main shortenings occurred earlier, at 30, in females and later, at 60, in males. In females, LPT values in full extension were significantly longer than those measured at other flexion angles. In male subjects, significant differences in LPT values were found between full extension versus 90 (p &lt
0.001) and full flexion (p &lt
0.001), and between 60 versus 90 (p = 0.030) and full flexion (p = 0.030). Conclusion: These differences might influence the gender-specific complications related to the extensor mechanism after TKA. These data provide useful information for surgeons attempting to achieve a satisfactory balance between joint gaps in the patellar reduced position intraoperatively. © 2013 The Japanese Orthopaedic Association.

DOI： 10.1007/s00776-013-0377-2

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Purpose: It is still controversial whether simultaneous or staged total knee arthroplasty (TKA) is most desirable for patients with bilateral knee osteoarthritis. We retrospectively evaluated changes in balance among patients with bilateral osteoarthritis who underwent staged TKA using a gravicorder. Methods: Patients were stratified into two groups: the unilateral group (UG) (22 patients) consisted of patients who did not undergo a second TKA within 24 months of the first TKA, and the bilateral group (BG) (20 patients) were those who had a second TKA within 12 months after initial TKA. Results: The mean gravity center position (GCP), which indicates the translation of GCP in the mediolateral direction between pre- and post-TKA shifted to the operative side in both groups after initial surgery. While the GCP was maintained on the same side in UG over 2 years follow-up, in BG it moved to the opposite side and approached a central position after the second TKA. Locus length of GCP (LG), which indicates postural control function by proprioceptive reflex showed significant improvement after initial TKA in UG, while BG showed significant improvement after the second TKA. Conclusions: The degree of LG improvement after initial TKA may indicate the necessity of a second TKA for patients with bilateral osteoarthritis. The current study suggests that simultaneous bilateral TKA is not always necessary for patients with bilateral knee arthritis, and that properly performed rehabilitation such as improving postural sway after initial TKA might attenuate the timing for the second TKA. © 2013 The Japanese Orthopaedic Association.

DOI： 10.1007/s00776-013-0430-1

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Background: Incident reporting is the most common method for detecting adverse events in a hospital. However, under-reporting or non-reporting and delay in submission of reports are problems that prevent early detection of serious adverse events. The aim of this study was to determine whether it is possible to promptly detect serious injuries after inpatient falls by using a natural language processing method and to determine which data source is the most suitable for this purpose.
Methods: We tried to detect adverse events from narrative text data of electronic medical records by using a natural language processing method. We made syntactic category decision rules to detect inpatient falls from text data in electronic medical records. We compared how often the true fall events were recorded in various sources of data including progress notes, discharge summaries, image order entries and incident reports. We applied the rules to these data sources and compared F-measures to detect falls between these data sources with reference to the results of a manual chart review. The lag time between event occurrence and data submission and the degree of injury were compared.
Results: We made 170 syntactic rules to detect inpatient falls by using a natural language processing method. Information on true fall events was most frequently recorded in progress notes (100%), incident reports (65.0%) and image order entries (12.5%). However, F-measure to detect falls using the rules was poor when using progress notes (0.12) and discharge summaries (0.24) compared with that when using incident reports (1.00) and image order entries (0.91). Since the results suggested that incident reports and image order entries were possible data sources for prompt detection of serious falls, we focused on a comparison of falls found by incident reports and image order entries. Injury caused by falls found by image order entries was significantly more severe than falls detected by incident reports (p<0.001), and the lag time between falls and submission of data to the hospital information system was significantly shorter in image order entries than in incident reports (p<0.001).
Conclusions: By using natural language processing of text data from image order entries, we could detect injurious falls within a shorter time than that by using incident reports. Concomitant use of this method might improve the shortcomings of an incident reporting system such as under-reporting or non-reporting and delayed submission of data on incidents.

DOI： 10.1186/1472-6963-12-448

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Background: Despite recent studies reporting on the results of prospective intentional sublobar resection for patients with small non-small cell lung cancer (NSCLC), few studies have investigated predictors for prognosis or recurrence exclusively in patients undergoing intentional sublobar resection. Methods: We retrospectively reviewed 223 patients with small (2 cm or less) peripheral NSCLC who underwent intentional segmentectomy at the Niigata Cancer Center Hospital between 1992 and 2009. The significant demographic, clinical, and pathologic factors identified with the log rank test in univariate analyses were analyzed with the Cox proportional hazards regression model to examine independent predictors for prognosis and recurrence in multivariate analysis. Results: The 5-year and 10-year overall survival rates were 89.6% and 81.0%, respectively, and the 5-year and 10-year recurrence-free probabilities were 91.1% and 91.1%, respectively. Eight patients had locoregional recurrence, and 12 had distant recurrence. Multivariate analyses revealed that age more than 70 years (hazard ratio [HR] 2.389), male (HR 2.750), more than 75% consolidation/tumor ratio on high-resolution computed tomography (HR 2.750), and lymphatic permeation (HR 5.618) were independent poor prognostic factors, and lymphatic permeation (HR 16.257) was an independent predictor for recurrence. Conclusions: The factors related to upstaging on pathologic diagnosis were not identified as independent predictors
therefore, the current patient selection criterion seems reasonable. If lymphatic permeation is present on pathologic findings, careful follow-up is recommended. The predictors identified in this study will support assessment and interpretation of the results of ongoing prospective randomized trials of lobar versus sublobar resection in patients with small peripheral NSCLC. © 2012 The Society of Thoracic Surgeons.

DOI： 10.1016/j.athoracsur.2012.02.093

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This study evaluated changes in the lower extremity 3-dimensional load-bearing mechanical axes in the anteroposterior and mediolateral directions before and at 3 weeks after mobile-bearing total knee arthroplasty. The effects of the degrees of anteroposterior constraint of the designs on the location of the load-bearing mechanical axis at the knee joint level were also assessed. We evaluated 151 knees from 134 patients with 74 knees receiving meniscal bearing-type and 77 knees receiving rotating platform-type prostheses. In the mediolateral direction, both designs showed significant improvements, whereas in the anteroposterior direction, they revealed no improvements postoperatively and were worsened significantly in meniscal bearing type. Differences in the degree of bone and soft tissue involvement for the correction of alignment may explain the findings. © 2012 Elsevier Inc.

DOI： 10.1016/j.arth.2011.12.013

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Canadian Center of Science and Education  

Severe injuries such as intracranial hemorrhage (ICH) are the most serious problem after falls in hospital, but they have not been considered in risk assessment scores for falls. We tried to determine the risk factors for ICH after falls in 20,320 inpatients (696,364 patient-days) aged from 40 to 90 years who were admitted to a tertiary-care university hospital. Possible risk factors including STRATIFY risk score for falls and FRAX risk score for fractures were analyzed by univariate and multivariate analyses. Fallers accounted for 3.2% of the patients, and 5.0% of the fallers suffered major injuries, including peripheral bone fracture (59.6%) and ICH (23.4%). In addition to STRATIFY, FRAX was significantly associated not only with bone fractures but also ICH. Concomitant use of risk score for falls and risk score for fractures might be useful for the prediction of major injuries such as ICH after falls.

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The aim of this study was to compare the accuracy of preoperative templating in total knee arthroplasty (TKA) using conventional two-dimensional (2D) and computed tomography (CT)-based three-dimensional (3D) procedures, and to confirm the necessity of 3D evaluation for preoperative planning. One hundred consecutive primary TKAs were analyzed. Preoperative templating was performed for each TKA using both conventional 2D radiographs and a CT-based 3D image model created using KneeCAS software. Accuracies with regard to the predicted and actual implant sizes were determined for each procedure. The 3D procedure was found to be more accurate (59%) than the 2D procedure (56%) in predicting implant size, but the difference was not statistically significant (p=0.67). Computer-assisted surgery systems are often used for preoperative planning in TKA. However, our results do not support the superiority of 3D preoperative templating over 2D conventional evaluation in predicting implant size. Thus, 3D templating may not be necessary for preoperatively predicting implant size in TKA, and can only be used as an approximate guide. © 2012 Informa UK Ltd All rights reserved.

DOI： 10.3109/10929088.2011.651488

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Background Despite the advances of asthma management and the accompanying improved asthma control, many problems related to asthma management still remain. The Niigata Asthma Treatment Study Group has been regularly collecting information via surveys since 1998 using a questionnaire, on problems related to asthma management
various studies on asthma management have been reported using data from the questionnaire. Methods The aim of this study was to investigate the changes in asthma control and management for every two-year period using the data from 1998 to 2008
future problems requiring resolution were extracted and discussed. Results The number of cases surveyed each year was about 3,000 (2,593-3,347 cases). The changes in the data from 1998 to 2008, including asthma attacks and symptoms rate, indicated the improvement of asthma control with the spread of medication according to the guidelines
of particular note, there was a 24.1% increase in the usage rate of inhaled corticosteroids during the study period. From 2002 to 2008, however, some asthmatic conditions seemed to show no improvement with regards to asthma control related to the rates of changes in peak flow meter use, leukotriene receptor antagonist use and oral sustained-released theophylline use. Moreover, there was no decrease in the occurrence of emergency episodes related to asthma deaths. Conclusion In the actual clinical setting, asthma control seems to be progressing well with the appropriate changes of medication according to the guidelines, and in part due to inhaled corticosteroid use. However, there were two problems which need to be addressed: 1) no improvement in some asthmatic conditions and 2) the occurrence of emergency episodes related to asthma deaths. In the future, it will be necessary to manage asthma in view of these points. © 2012 The Japanese Society of Internal Medicine.

DOI： 10.2169/internalmedicine.51.6586

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INTRODUCTION:: Even for patients with clinical N0 non-small-cell lung cancer (NSCLC), several invasive tests are available to pathologically confirm the presumptive mediastinal stage by radiologic modalities. The aim of this study was to determine a high-risk population for mediastinal nodal metastasis in patients with clinical stage IA NSCLC, which would be suitable for mediastinal staging by invasive modalities, such as mediastinoscopy or endobronchial ultrasound-guided transbronchial needle aspiration. METHODS:: We retrospectively reviewed peripheral clinical stage IA NSCLC patients who had undergone surgical resection with systematic mediastinal lymphadenectomy from 1998 to 2011. To identify predictors for mediastinal nodal metastasis, univariate and multivariate logistic regression analyses were performed. For the significant factors, optimal cutoff points were determined with a receiver operating characteristic analysis. RESULTS:: Among the 894 patients eligible for this study, the overall prevalence of mediastinal nodal metastasis was 7.5%. The following four predictors for mediastinal nodal metastasis were identified: age, preoperative serum carcinoembryonic antigen level, tumor size on preoperative radiologic findings, and consolidation/tumor ratio on high-resolution computed tomography. Of the patients with all four predictors identified by the multivariate analyses and receiver operating characteristic analyses (age ≤67 years, carcinoembryonic antigen 3.5 ng/ml, tumor size 2.0 cm, and consolidation/tumor ratio 89%), the prevalence of mediastinal nodal metastasis was 33.8%. CONCLUSIONS:: Among the clinical stage IA NSCLC patients in whom all four predictors were identified, one third of the patients showed mediastinal nodal metastasis, and thus, those patients should be a target for mediastinal node assessment by invasive modalities, such as mediastinoscopy or endobronchial ultrasound-guided transbronchial needle aspiration. Copyright © 2012 by the International Association for the Study of Lung Cancer.

DOI： 10.1097/JTO.0b013e31825871de

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Purpose: This study evaluated the changes in the range of motion (ROM) with time postoperatively. Method: The pre- and intraoperative ROM was compared with the ROM 3, 6, 12, and 24 months postoperatively to clarify the effects of posterior cruciate ligament-retaining (PCLR) and posterior cruciate ligament-sacrificing (PCLS) prostheses on the ROM. The changes in the ROM in PCLR (n = 57) and PCLS (n = 51) mobile-bearing total knee arthroplasties for osteoarthritis patients for whom complete data were available were examined. Results: No significant difference was seen between the two prostheses at any time point. Nevertheless, the ROM 24 months after PCLR and PCLS prostheses could be predicted statistically from the ROM after 6 and 3 months, respectively. Conclusion: This study showed the effects of retention of the PCL and the degree of its functional recovery on postoperative ROM for the two prostheses. Level of Evidence: Systematic review, Level II. © 2011 Springer-Verlag.

DOI： 10.1007/s00167-011-1395-2

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Background. Total and antigen-specific IgE levels vary greatly with age
however, it is unclear whether they are more closely related to patient age or birth cohort. Objective. To determine whether birth cohort or age was more strongly correlated with total and specific IgE levels. Methods. We retrospectively examined the medical records of 5136 asthma patients who were treated at the Niigata Allergic Disease Research Institute Outpatient Clinic during the period from 1997 to 2005. The subjects were divided into four birth cohorts based on their year of birth: the first cohort was born in 1935 or earlier, the second in 1936-1955, the third in 1956-1975, and the fourth in 1976 or later. Their total IgE level and mite-, cedar-, and Candida albicans (Candida)-specific IgE levels were measured using the CAP RAST fluoroenzyme immunoassay test. Results. Univariate analysis revealed that total IgE level and mite-, cedar-, and Candida-specific IgE levels significantly decreased (p &lt
.001) with advancing age. In addition, there were significantly higher IgE levels in later birth cohorts (p &lt
.01). On multivariate analysis, there were associations of total IgE level and mite-and cedar-specific IgE levels with both age and birth cohort. However, there was no significant association between Candida-specific IgE antibody level and either age or birth cohort. Conclusions. The associations of total and specific IgE levels with age and birth cohort were different. Thus, in comparing the results of IgE antibody testing done in different years, even for patients of the same age, the possibility of a birth cohort effect on IgE levels should be considered. © 2011 Informa Healthcare USA, Inc.

DOI： 10.3109/02770903.2011.558152

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The purpose of this study was to clarify the changes between preoperation and postoperation in each posterior condylar offset (PCO) using computed tomography (CT) and to compare them to conventional radiographic (x-ray) evaluation in total knee arthroplasty. One hundred nine knees in 97 patients were evaluated. The medial PCO was significantly larger before surgery. The lateral PCO was significantly larger after surgery. Changes in the PCO on x-ray showed no significant correlation with the changes observed in the CT-evaluated medial (R = 0.028) and lateral PCO (R = 0.190). Changes in PCO observed by x-ray did not reflect those of the medial or lateral condyles on CT. We recommend CT-based evaluation of PCO by condyle when assessing the influence of PCO on range of motion following total knee arthroplasty.

DOI： 10.1016/j.arth.2010.05.023

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BACKGROUND Despite the use of inhaled corticosteroid (ICS) becoming increasingly widespread, many problems related to asthma management still need to be addressed. One of them, obesity, has been reported to exert a harmful influence on asthma control. However, there have been few reports focusing not only on both obesity and its influence on Japanese asthma patients but also on the Japanese definition of obesity, as defined by the Japan Society for the Study of Obesity (JASSO). AIMS & METHODS The aim of this study was to confirm the influence of obesity, as defined by the JASSO, on asthma management in Japanese asthmatic patients. Using data from the Niigata Asthma Treatment Study Group 2008 questionnaire survey, differences between the "normal" group (18.5 kg/m(2) </= BMI <25 kg/m(2)) and the "obese" group (25 kg/m(2) </= BMI) were analyzed. RESULTS There was a significantly lower step 1 rate (19.4% v.s. 26.8%) and a higher proportion of patients using inhaled salmeterol (43.6% v.s. 35.8%) and leukotriene receptor antagonist (49.8% v.s. 40.8%) in the obese group relative to the normal group, although there were no significant differences in indicators of asthma control, including

DOI： 10.2169/internalmedicine.50.5474

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In Japan, the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in 2010. To assess the effects of PCV7 on invasive pneumococcal infection in children, a population-based prospective survey has been conducted in 10 prefectures. As a part of the study, blood and nasopharyngeal isolates from children admitted to the Shibata Hospital, Niigata Prefecture, were analyzed for determining the serotypes, their susceptibilities to antimicrobial agents, and multilocus sequence types. Sixteen blood isolates were obtained from October 2007 to December 2009. Sixty-three nasopharyngeal isolates were obtained from the posterior nares of 118 children with pneumonia from April to September 2008. The coverage rates of the blood and nasopharyngeal isolates for PCV7 were 81.3z and 57.1z, respectively. Although none of these children had received PCV7, serotype 19A isolates were recovered from 12.5z (2/16) of the blood samples and 12.7z (8/63) of the nasopharyngeal samples. The sequence type of a nasopharyngeal isolate of serotype 19A was ST320, and the minimum inhibitory concentration of penicillin G was 4 μg/mL. In addition to the continuous prospective survey of pneumococcal infection, early introduction of the 13-valent conjugate vaccine, in which the 19A conjugate is included, will be necessary in Japan.

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BACKGROUND: The relationship between age at onset of adult asthma and asthma severity has not been comprehensively investigated. METHODS: A total of 4161 patients with asthma (1578 men) aged 16 years or older were classified into 4 groups according to their age at asthma onset: group A (16-19 years), group B (20-39 years), group C (40-59 years), and group D (>60 years). We examined the relationship between the age at onset and severity of asthma among the 4 groups and analyzed factors associated with asthma severity. RESULTS: The severity of asthma rose with increasing age at onset, and vice-versa. Factors associated with severity of adult onset asthma were analyzed using multiple regression analysis. Asthma duration, total serum IgE level, smoking status, and age at onset were strongly associated with asthma severity. Age at onset was independently associated with the severity of adult-onset asthma. CONCLUSION: Our findings indicate that asthma severity is positively associated with age at onset in patients with adult-onset asthma.

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BACKGROUND: The relationship between the duration and severity of asthma has not been comprehensively investigated. METHODS: We examined the relationship between duration of asthma and asthma severity among 4776 patients with asthma: 608 with childhood-onset persistent asthma (12.7%), 187 with adolescent-onset asthma (3.9%), and 3981 with adult-onset asthma (83.4%). The assessment of asthma severity was based on the Japanese Guidelines for The Diagnosis and Treatment of Allergic Diseases, 2007 (JGL 2007). RESULTS: Asthma severity was assessed at 2 years, 3 to 10 years. 11 to 20 years, and 21 years or longer after disease onset. Disease severity significantly increased with greater asthma duration (p<0.001). This relationship was not affected by serum total IgE concentration (<300 IU/ml vs > or = 300 IU/ml), smoking status, house dust mite-specific serum IgE antibody level, or gender. CONCLUSION: Our findings suggest that bronchial asthma is a disease that worsens over time.

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BACKGROUND: The prevalence of elevated total and specific IgE antibody levels among Japanese adults with bronchial asthma has not been comprehensively investigated. We examined the prevalence of IgE levels in patients with asthma, and analyzed factors that are associated with elevated levels of IgE. METHODS: A total of 5067 patients with asthma (2047 were men) aged 16 or older and who had visited our clinic during a recent 9-year period (1997 through 2005) were classified into 4 birth period (groups, G) according to their year of birth: G1 (before 1926), G2 (1926 to 1945), G3 (1946 to 1965), and G4 (after 1965). First, we investigated the prevalence of elevated total IgE level (> or = 300 IU/mL) and the prevalence rates of specific IgE antibodies to house dust mites (mite), cedar pollen (cedar), and Candida albicans (Candida). Then, we investigated trends in the prevalence of antibodies among the 4 age groups during a 9-year period. RESULTS: 1. The prevalence of elevated levels of total IgE and specific IgE antibodies to mites and cedar pollen significantly increased in ascending order from G1 to G4. 2. Compared with women, men had a significantly higher prevalence of elevated l

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Background: Falls are very common accidents in a hospital. Various risk factors and risk assessment tools are used to predict falls. However, outcomes of falls such as bone fractures have not been considered in these risk assessment tools, and the performance of risk assessment tools in a Japanese hospital setting is not clear.
Methods: This was a retrospective single-institution study of 20,320 inpatients aged from 40 to 90 years who were admitted to a tertiary-care university hospital during the period from April 2006 to March 2009. Possible risk factors for falls and fractures including STRATIFY score and FRAX (TM) score and information on falls and their outcome were obtained from the hospital information system. The datasets were divided randomly into a development dataset and a test dataset. The chi-square test, logistic regression analysis and survival analysis were used to identify risk factors for falls and fractures after falls.
Results: Fallers accounted for 3.1% of the patients in the development dataset and 3.5% of the patients in the test dataset, and 2.6% and 2.9% of the fallers in those datasets suffered peripheral fractures. Sensitivity and specificity of the STRATIFY score to predict falls were not optimal. Most of the known risk factors for falls had no power to predict fractures after falls. Multiple logistic analysis and multivariate Cox's regression analysis with time-dependent covariates revealed that FRAX (TM) score was significantly associated with fractures after falls.
Conclusions: Risk assessment tools for falls are not appropriate for predicting fractures after falls. FRAX (TM) might be a useful tool for that purpose. The performance of STRATIFY to predict falls in a Japanese hospital setting was similar to that in previous studies.

DOI： 10.1186/1472-6963-10-106

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Background: The aim of this study was to identify factors responsible for childhood-onset persistent asthma and childhood-onset asthma relapsing in adulthood. Methods: We compared a number of potential risk factors for asthma among 608 patients with childhood-onset persistent asthma (onset at 15 years of age or younger) and 286'patients with childhood-onset asthma (onset at 20 years or younger) that had relapsed "after a period of remission longer than 2 years. Results: Multiple linear regression analysis revealed that the factors associated with childhood-onset persistent asthma were a past or present history of allergic rhinitis (p = 0.001) and high serum total IgE concentration (≥300IU/ml
p = 0.007). The factors associated, with relapse of childhood-onset asthma were female sex {p = 0.001), younger onset age (p = 0.036), and smoking (current or former: p&lt
0.001). Conclusion: Our findings indicate that a past or present history of allergic rhinitis and high serum IgE level are significant risk factors for childhood-onset persistent asthma, and that female sex and a history of smoking are risk factors for relapse of childhood-onset asthma Fortunately, exposure to r tobacco smoke is a controllable risk factor. © 2010 Japanese Society of Allergology.

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Background. We previously demonstrated a negative effect of cardiopulmonary bypass (CPB) in a canine model of single-lung graft function and an improved effect with ultrafiltration during CPB.
Objective. To investigate the mechanism of these effects, focusing on cytokines and pulmonary surfactants using real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).
Materials and Methods: Fifteen left-sided single-lung transplant procedures were performed in pairs of dogs. The animals were divided into 3 groups. In one group, transplantation was performed without CPB (non-CPB group); in a second group, transplantation was performed with CPB and CPB flow was decreased slowly and pulmonary artery pressure was controlled (CPB group; and in the third group, transplantation was performed with CPB and ultrafiltration (CPB+UF group). Grafted lung specimens were harvested for RT-PCR of cytokines (IL-6, IL-8, and IL-10) and surfactant proteins (SP-A, SP-B, and SP-C).
Results. Real-time quantitative RT-PCR demonstrated increased IL-6 expression in the CPB group compared with the non-CPB group. IL-6 gene expression was suppressed and pulmonary surfactant restored using ultrafiltration. Gene expression of surfactant protein (SP)-A, SP-B, and SP-C was decreased in the CPB group compared with normal lung and ultrafiltration groups, which demonstrated sustained gene expression of SP-A and SP-B.
Conclusion. Cardiopulmonary bypass has negative effects on grafts; however, ultrafiltration attenuates acute lung dysfunction by decreasing the inflammatory response and increasing pulmonary surfactant.

DOI： 10.1016/j.transproceed.2009.04.010

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The epsilon 4 allele of the apolipoprotein E gene (APOE) is unequivocally recognized as a genetic risk factor for late-onset Alzheimer's disease (LOAD). Recently, single-nucleotide polymorphisms (SNPs) of the GRB2-associated binding protein 2 gene (GAB2) were shown to be associated with LOAD in Caucasians carrying the APOE-epsilon 4 allele through a genome-wide association study. Here, we attempted to replicate the finding by genotyping these SNPs in a large clinical cohort of Japanese. We observed no association of any of the SNPs with LOAD. GAB2 may not be a disease susceptibility gene for LOAD in Japanese.

DOI： 10.1038/ejhg.2008.181

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Background: Since the late 1980s, the policy of the Japanese government regarding physician manpower has been to decrease the number of medical students. However, the shortage of doctors in Japan has become a social problem in recent years. The aim of this study was to compare the numbers of physicians in Japan between 1996 and 2006 and the trends in distribution of physicians.
Methods: The time trends in number and distribution of physicians between 1996 and 2006 were analyzed. Gini coefficient, Atkinson index and Theil index were used as measures for mal-distribution of physicians to population. The distribution of physicians was visualized on a map by using geographic information system (GIS) software.
Results: The total number of physicians increased every year in the period from 1996 to 2006 but has remained below the international standard. All three measures of mal-distribution of physicians worsened after 2004, and the worsening was remarkable in the distribution of physicians working at hospitals. The number of physicians working at hospitals has significantly increased in urban areas but not in areas with low population densities. When medical interns were excluded from calculation, the measures of mal-distribution improved.
Conclusion: The problem of a doctor shortage in Japan is linked to both the shortage of absolute number of physicians and the mal-distribution of hospital physicians. The new postgraduate internship system might worsen this situation.

DOI： 10.1186/1475-9276-8-5

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A preoperative quantitative evaluation of soft tissues is helpful for planning total knee arthroplasty, in addition to the conventional clinical examinations involved in moving the knee manually. We evaluated preoperative coronal laxity with osteoarthritis in patients undergoing total knee arthroplasty by applying a force of 150 N with an arthrometer. We examined a consecutive series of 120 knees in 102 patients. The median laxity was 0 degrees in abduction and 8 degrees in adduction. The femorotibial angle on non-weight-bearing standard anteroposterior radiographs was 180 degrees and correlated with both abduction (r=-0.244, p=0.007) and adduction (r=0.205, p=0.025) laxity. The results of a regression analysis suggested that the femorotibial angle is helpful for estimating both laxities. Considering the many reports on how to obtain well-balanced soft tissues, stress radiographs might help to improve the preoperative planning for gaining the optimal laxity deemed appropriate by surgeons.

DOI： 10.1007/s00264-007-0467-x

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Motivation: A two-stage association study is the most commonly used method among multistage designs to efficiently identify disease susceptibility genes. Recently, some SNP studies have utilized more than two stages to detect disease genes. However, there are few available programs for calculating statistical powers and positive predictive values (PPVs) of arbitrary n-stage designs.
Results: We developed programs for a multistage case-control association study using R language. In our programs, input parameters include numbers of samples and candidate loci, genome-wide false positive rate and proportions of samples and loci to be selected at the k-th stage (k = 1,..., n). The programs output statistical powers, PPVs and numbers of typings in arbitrary n-stage designs. The programs can contribute to prior simulations under various conditions in planning a genome-wide association study.

DOI： 10.1093/bioinformatics/btn616

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Allergology  

Background: Inhaled corticosteroid (ICS) has played an important role in the management of asthma. Although several kinds of ICSs are currently available, there is no established strategy for ICS selection. Methods: Using the data from the 2004 questionnaire surveys by the Niigata Asthma Treatment Study Group, we analyzed relationships between each patient and the ICS employed on the basis of patient background, asthma control and treatment, and indicated characteristics of ICS selection by the physician. Results: Of 2852 cases, 2279 (79.9%) were ICS users, and 1513 (66.4% of ICS users) were classified as being in the fluticasone propionate (FP) group, 438 (19.2%) in the budesonide (BUD) group, and 240 (10.5%) in the hydrofluoroalkane-beclometasone (HFA-BDP) group, indicating that FP was a standard ICS in this study. The mean age was significantly lower in the BUD group (52.3+/-18.2 years) and was significantly higher in the HFA-BDP group (59.9+/-17.0 years) than that in the FP group (55.8+/-16.6 yaers). The proportion of female patients was significantly higher not in the HFA-BDP (46.5%) but in the BUD group (59.0%) than in the FP group (51.1%). These results indicated that BUD was frequently prescribed to young female and HFA-BDP was employed in the elderly patients irrespective of gender compared with FP. Conclusions: Our study indicates that ICS selection is reasonably adapted to each patient's background at least in the surveyed area. We need to elucidate the characteristics of ICS selection further in the future as new ICS and devices are developed. ©2009 Japanese Society of Allergology.

DOI： 10.2332/allergolint.08-OA-0077

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

Aim: This study was undertaken 5 months after the 2004 Niigata-Chuetsu earthquake in Japan to assess factors that impacted on psychological distress and its recovery.
Methods: Three thousand and twenty-six adult victims who lived in temporary shelter and in seriously damaged areas were evaluated by questionnaire. The questionnaire queried subject profile, degree of house damage, health status, and psychological distress using a 5-point scale before, immediately and 5 months after the earthquake.
Results: Immediately after the earthquake, 59.3% of the subjects had psychological distress. At 5 months after the earthquake, however, this percentage decreased to 21.8%. The psychological distress immediately after the earthquake was significantly serious in victims who: (i) were female; (ii) felt stronger fear of the earthquake and the aftershocks; (iii) lived at home or office after the earthquake; and (iv) were injured due to the earthquake or suffered from sickness after the earthquake. In contrast, the factors impairing psychological recovery 5 months after the earthquake were as follows: (i) being with unfamiliar member(s) during the night after the earthquake; (ii) serious house damage; (iii) living in temporary shelter or at a relative's home after the earthquake; and (iv) physical illness after the earthquake.
Conclusion: Despite differences between disasters, these results were consistent with those in some previous studies and may be useful for long-term mental care support.

DOI： 10.1111/j.1440-1819.2008.01842.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING  

It is difficult to achieve a sustained virologic response from antiviral therapy for genotype 1 hepatitis C virus-infected patients without a sufficient virologic response in the early weeks after treatment. However, a recent study has reported on the effectiveness of an extended course of treatment with peginterferon alpha-2a plus ribavirin for slow virologic responders. The aim of this study was to evaluate the economic impact of an extended course of treatment. A Markov cohort model of hepatitis C was designed in order to demonstrate the clinical states, based on the assigned transition probabilities over 30 years. The slow virologic responders treated with an extended 72-week course of therapy could increase by 0.55 the quality-adjusted life years (=15.35-14.80) and reduce the lifetime cost by $2762 (=71 559-69 438) in comparison with those treated by the standard 48-week course. One-way sensitivity analyses did not change the cost-effectiveness. Therefore, the extended 72 weeks of treatment with peginterferon alpha-2a plus ribavirin for slow virologic responders could be cost-effective in comparison with the standard 48 weeks of treatment.

DOI： 10.1111/j.1365-2893.2007.00943.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Purpose. The objectives of this study were to identify the clinicopathologic characteristics and prognostic factors of small (2 cm or less in diameter) adenocarcinomas, and furthermore to assess the acceptability of performing a limited pulmonary resection in such patients.
Methods. We retrospectively reviewed 523 cases of cT1N0M0 peripheral adenocarcinoma measuring 2 cm or less on diagnostic images treated by a complete resection between 1991 and 2004.
Results. The overall 5-year survival rate of the patients with small adenocarcinomas was 83.6%. Univariate and multivariate analyses identified an older age, male sex, wedge resection, advanced stage, and Noguchi classification of C, D, E, or F as independent prognostic factors that adversely affected overall survival. However, there were no significant differences in the survival according to surgical procedure in the patients whose tumors had a maximum diameter of 1.0 cm or less or in Noguchi type A and B cases.
Conclusion. Age, sex, surgical procedure, p-stage, and Noguchi classification were independent prognostic factors for survival in patients with small adenocarcinomas. A segmentectomy is therefore considered to be an acceptable alternative to a lobectomy for adenocarcinomas of 2 cm or less in diameter. A wedge resection may be acceptable for tumors measuring 1 cm or less in diameter or Noguchi type A and B tumors.

DOI： 10.1007/s00595-007-3594-5

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Focal spike activities in Panayiotopoulos syndrome involve all brain regions in electroencephalography, and commonly reveal multiple foci, often through occipital predominance. To investigate correlations between developmental brain maturation and spike origin in Panayiotopoulos syndrome, we evaluated age-related or duration-related magnetoencephalographic spike localization in 25 patients with Panayiotopoulos syndrome. Regarding age at examination, patients with frontal spikes were significantly older than patients with spikes on rolandic, parieto-occipital, or calcarine sulci. Occipital spikes were classified into two subgroups, located at the calcarine sulcus and parieto-occipital sulcus. Both calcarine and parieto-occipital localizations were seen in patients around the same age. Follow-up magnetoencephalography was performed on three patients, and demonstrated shifting localization or disappearance of magnetoencephalographic spikes. These results suggest that the location of spike discharges is not directly related to seizure symptoms, but instead indicates maturation-related cortical hyperexcitability in patients with Panayiotopoulos syndrome. (c) 2008 by Elsevier Inc. All rights reserved.

DOI： 10.1016/j.pediatrneurol.2007.08.020

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN  

Objectives: Simultaneous dealing of hundreds of thousands of single nucleotide polymorphisms (SNPs) in genome-wide association studies is laborious. The aim of our study is to develop a method to decrease the number of candidate SNPs prior to the genotyping of study subjects.
Methods. We created virtual genotype data on case and control subjects from data of the International HapMap Project by using haplotype-based simulation method. We repeated virtual case-control association studies and selected candidate SNPs. We applied the selected SNPs to previously published genetic case-control studies. Sensitivity to detect association with causative genes using our method was compared to the original studies and results using tag SNPs.
Results. We found a discrete distribution pattern of SNPs, which was able to produce significant results in case-control association studies. The number of candidate SNPs that we selected was 24.7% of the number of the original set of SNPs, We applied this method to previously published genetic case-control studies and found that the use of candidate SNPs improved the sensitivity for detecting significant alleles, both compared to the original studies and to the use of tag SNPs. The results were not affected by the difference of the diseases and genes involved.
Conclusions. Our simulation-based approach has advantages of reducing costs and improving performance to detect significant alleles. This method can be used without considering the specific disease and genes involved.

DOI： 10.3414/ME9129

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

Alzheimer's disease (AD), the most common form of dementia in the elderly, was found to exhibit a trend toward a higher risk in females than in males through epidemiological studies. Therefore, we hypothesized that gender-related genetic risks could exist. To reveal the ones for late-onset AD (LOAD), we extended our previous genetic work on chromosome 10q (genomic region, 60-107 Mb), and single nucleotide polymorphism (SNP)-based genetic association analyses were performed on the same chromosomal region, where the existence of genetic risk factors for plasma A beta 42 elevation in LOAD was implied on a linkage analysis. Two-step screening of 1140 SNPs was carried out using a total of 1408 subjects with the APOE-epsilon 3*3 genotype: we first genotyped an exploratory sample set (LOAD, 363; control, 337), and then genotyped some associated SNPs in a validation sample set (LOAD, 336; control, 372). Seven SNPs, spanning about 38 kb, in intron 9 of CTNNA3 were found to show multiple-hit association with LOAD in females, and exhibited more significant association on Mantel-Haenszel test (allelic P-values(MH-F) = 0.000005945-0.0007658). Multiple logistic regression analysis of a total of 2762 subjects (LOAD, 1313; controls, 1449) demonstrated that one of the seven SNPs directly interacted with the female gender, but not with the male gender. Furthermore, we found that this SNP exhibited no interaction with the APOE-epsilon 4 allele. Our data suggest that CTNNA3 may affect LOAD through a female-specific mechanism independent of the APOE-epsilon 4 allele.

DOI： 10.1093/hmg/ddm244

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

An accurate diagnosis of acute appendicitis in the early stage is often difficult, and decision support tools to improve such a diagnosis might be required. This study compared the levels of accuracy of artificial neural network models and logistic regression models for the diagnosis of acute appendicitis. Data from 169 patients presenting with acute abdomen were used for the analyses. Nine variables were used for the evaluation of the accuracy of the two models. The constructed models were validated by the ".632+ bootstrap method". The levels of accuracy of the two models for diagnosis were compared by error rate and areas under receiver operating characteristic curves. The artificial neural network models provided more accurate results than did the logistic regression models for both indices, especially when categorical variables or normalized variables were used. The most accurate diagnosis was obtained by the artificial neural network model using normalized variables.

DOI： 10.1007/s10916-007-9077-9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：LIPPINCOTT WILLIAMS & WILKINS  

Objective Recent studies have reported the effectiveness of shorter courses of treatment with peginterferon alpha-2b plus ribavirin for patients with chronic hepatitis C, who achieved a rapid virologic response (RVR), defined as undetectable hepatitis C virus (HCV-) RNA at week 4. The aim of this study was to evaluate the cost-effectiveness of the new protocol for treatment, from the perspective of RVR.
Methods A cost-effectiveness analysis based on the rate of sustained virologic response was performed. A Markov cohort model of hepatitis C was constructed to demonstrate the clinical states on the basis of the assigned transition probabilities over 30 years. The treatment strategies were classified into five subgroups taking into consideration the viral genotypes, viral load, and RVR. The lifetime costs and quality-adjusted life years (QALYs) were compared between the new and standard protocols for treatment.
Results Genotype 1-infected patients in the new protocol for treatment compared with the standard one could prolong OALYs by 0.33 and reduce lifetime cost by (sic) 5993. Genotype 2 or 3-infected patients in the new protocol for treatment compared with the standard one could prolong QALYs by 0.02 and reduce lifetime cost by (sic)2851.
Conclusion Treatment strategies that consider viral load and RVR for patients with a low viral load infected with genotype 1 and those infected with genotype 2 or 3 are more cost-effective compared with the standard protocol for treatment.

DOI： 10.1097/MEG.0b013e3282748f1f

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: Factor structure of the 12-item General Health Questionnaire (GHQ- 12) was studied by a survey of subjects who had experienced the 2004 Niigata-Chuetsu earthquake (6.8 on the Richter scale) in Japan.
Methods: Psychological distress was measured at two years after the earthquake by using GHQ-12 in 2,107 subjects (99.0% response rate) who suffered the earthquake. GHQ-12 was scored by binary, chronic and Likert scoring method. Confirmatory factor analysis was used to reveal the factor structure of GHQ-12. Categorical regression analysis was performed to evaluate the relationships between various background factors and GHQ-12 scores.
Results: Confirmatory factor analysis revealed that the model consisting of the two factors and using chronic method gave the best goodness-of-fit among the various models for factor structure. Recovery in the scale for the factor 'social dysfunction' was remarkably impaired compared with that of the factor 'dysphoria'. Categorical regression analysis revealed that various factors, including advanced age, were associated with psychological distress. Advanced age affected the impaired recovery of factor 'social dysfunction' score as well as total GHQ score.
Conclusion: The two-factor structure of GHQ-12 was conserved between the survey at five month and that at two years after the earthquake. Impaired recovery in the ability to cope with daily problems in the subjects who had experienced the earthquake was remarkable even at two years after the earthquake.

DOI： 10.1186/1471-2458-7-175

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING  

Objectives: We evaluated prostate-specific antigen (PSA) density of the prostatic volume (PSAD) estimated using transrectal ultrasonography (TRUS; TRUS-based PSAD), magnetic resonance imaging (MRI; MRI-based PSAD), and PSA density of the transition zone (TZ) volume (PSATZD) estimated using MRI (MRI-based PSATZD) in the diagnosis of prostate cancer (PCa).
Methods: One hundred and twenty patients, who were suspected to have PCa based on PSA, ranged between 4.1 and 20.0 ng/mL were enrolled in this study.
Results: The prostatic volume estimated using TRUS was smaller than the volume estimated using MRI by 11.4% in the patients with PSA levels ranging 4.1-20.0 ng/mL, 7.2% in those 4.1-10.0 ng/mL, and 15.7% in those 10.1-20.0 ng/mL, respectively. PSA levels were correlated with the prostatic volume estimated using TRUS and MRI, and TZ volume estimated using MRI in the patients without PCa; however, the level was not correlated with them in the patients with PCa. The area under the receiver operating characteristic curve of MRI-based PSAD was higher than that of TRUS-based PSAD; however, there was no statistical difference. Stepwise logistic regression analysis for the prediction of PCa by using PSA-related parameters confirmed that MRI-based PSATZD was the most significant predictor in patients with PSA levels in the range of 4.1-20.0 ng/mL (P < 0.001), the range of 4.1-10.0 ng/mL (P=0.002), and the range of 10.1-20.0 ng/mL (P < 0.001), respectively.
Conclusions: The prostatic volume estimated using TRUS was smaller than the volume estimated using MRI. MRI-based PSATZD is the most significant predictor in the four parameters.

DOI： 10.1111/j.1442-2042.2007.01686.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

DOI： 10.1016/j.genhosppsych.2006.09.006

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The purpose of this study was to assess the relationship between the clinical findings before starting treatment and the development quotient in children treated for congenital hypothyroidism. Patients with congenital hypothyroidism (n = 129) were divided into favorable and unfavorable groups according to intellectual performance. Children with congenital hypothyroidism generally have a similar intellectual outcome to that of healthy children. However, a low birth weight, the presence of complications, and a high serum thyroid-stimulating hormone value are the risk factors for unfavorable cases, who consistently have a development quotient score of less than 100. © 2007 Sage Publications.

DOI： 10.1177/0009922806289326

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN  

Objectives: The diagnosis of acute appendicitis is difficult, and a diagnostic error will often lead to either a perforation or the removal of a normal appendix. In this study, we constructed a Bayesian network model for the diagnosis of acute appendicitis and compared the diagnostic accuracy with other diagnostic models, such as the naive Bayes model, an artificial neural network model, and a logistic regression model.
Methods: The data from 169 patients, who suffered from acute abdominal pain and who were suspected of having an acute appendicitis, were analyzed in this study. Nine variables were used for the evaluation of the accuracy of the four models for the diagnosis of an acute appendicitis. The naive Bayes model, the Bayesian network model, an artificial neural network model, and a logistic regression model were used in this study for the diagnosis of acute appendicitis. These four models were validated by using the ".632 + bootstrap method" for resampling. The levels of accuracy of the four models for diagnosis were compared by the error rates and by the areas under the receiver operating characteristic curves.
Results: Through the course of illness, 50.9% (86 of 169) of the patients were diagnosed as having an acute appendicitis. The error rate was the lowest in the Bayesian network model, as compared with the other diagnostic models. The area under the receiver operating characteristic curve analysis also showed that the Bayesian network model provided the most reliable results.
Conclusion: The Bayesian network model provided the most accurate results in comparison to other models for the diagnosis of acute appendicitis.

DOI： 10.3414/ME9066

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Allergology  

Background: Perimenstrual asthma (PMA) has been documented in 30% to 40% of asthmatic women
the characteristics of PMA have also been well described. However, there have been few epidemiological investigations of PMA in practice. In this study, we analyzed PMA based on a questionnaire survey carried out in Japan and compared the results with those of studies reported previously. Methods: For 8 weeks from September through October 2004, a questionnaire survey was administered to patients with bronchial asthma and their attending physicians. The questionnaire surveyed asthma control, asthma-related emergencies and satisfaction in daily life. The attending physicians were questioned about patient profiles and medications. All female patients who were menstruating during the survey period and who were known to have asthma exacerbation related to menstruation were allocated to the PMA group
those who were not were allocated to the non-PMA group. Results: The rate of PMA in female patients who were menstruating during the survey period was 11.3% in this study. Characteristic features of the PMA group (n = 54) included more severe disease, worsened disease control and more aggressive patient management, including increased oral corticosteroid use compared with the non-PMA group. The rates of emergency episodes in the PMA group were higher than in the non-PMA group. There was a significant increase in aspirin intolerant asthma (AIA, 25.5%) in the PMA group compared with the non-PMA group (8.4%). Conclusions: Attention should be paid to the lack of knowledge regarding PMA in patients with asthma in actual clinical settings. The low rate of PMA reported in this study may be due to the study method using self-reports of PMA by patients without sufficient knowledge, and may not be an accurate representation of the actual incidence of the disease. The clinical similarity of PMA to AIA in this study may also provide a new insight into the mechanism of PMA. ©2007 Japanese Society of Allergology.

DOI： 10.2332/allergolint.O-06-475

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BLACKWELL PUBLISHING  

Recent studies have shown that B cells play a central role in the pathogenesis of systemic lupus erythematosus (SLE). Abnormal expression of molecules engaging in B-cell receptor (BCR) signaling and resultant hyperactivity of B cells has been reported in both mouse models of lupus and patients with SLE. CD72 on B cells is unique in that it regulates BCR signaling both positively and negatively. We analyzed the expression of CD72 protein and mRNA in peripheral blood B cells from adolescent patients with SLE. The expression level of CD72 on B cells of the patients was decreased compared with that on B cells of controls. Sequence analysis of CD72 mRNA showed significantly increased nucleotide mutations, including both nucleotide substitutions and deletions. Almost all (95.6%) of the CD72 transcripts from the patients had different nucleotide sequences from those of the wild type. About half (41.3%) of the mutations were point mutations located close to the sequence of the immunoreceptor tyrosine-based inhibitory motif (ITIM), which negatively regulates BCR signaling. These results indicate that increased nucleotide mutation of CD72 mRNA accounts for the decreased expression level of CD72 in B cells, and it might be related to hyperactivity of B cells in patients with SLE.

DOI： 10.1111/j.1399-3038.2006.00466.x

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Association for Medical Informatics  

The new inclusive payment system was introduced into acute inpatient care in main hospitals at universities to replace traditional fee-for-service payment system in 2003. The system created incentives to reduce length of stay of inpatients (LOS) and to urge early discharge to aftercare to shorten the LOS. Therefore, strong partnership with other medical facilities became more important for university hospitals. We studied the pattern of reverse referral from a university hospital to aftercare using geographic information system (GIS). We found that GIS is a useful tool to detect the spatial differences in partnership between the university hospital and other medical facilities.

DOI： 10.14948/jami.26.41

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Other Link： http://search.jamas.or.jp/link/ui/2006318622

Language：Japanese   Publishing type：Research paper (scientific journal)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MOSBY-ELSEVIER  

Objective: The purpose of this study was to investigate the effects of cardiopulmonary bypass and ultrafiltration on graft function in a canine single-lung transplantation model.
Methods: Fifteen left single-lung transplantations were done in weight-mismatched canine pairs. The animals were divided into 3 groups: group 1, in which transplantation was done without cardiopulmonary bypass; group 2, in which transplantation was done with cardiopulmonary bypass and in which the cardiopulmonary bypass flow was decreased slowly with controlled pulmonary artery pressure; and group 3, in which transplantation was done with cardiopulmonary bypass and ultrafiltration. Hemodynamic parameters and lung function were monitored for 6 hours after reperfusion. The grafts were harvested for histologic studies, myeloperoxidase assay, and real-time quantitive reverse transcription-polymerase chain reaction of mRNA encoding interleukin 6.
Results: The hemodynamic parameters were similar among the 3 groups. In group 1 Pa-O2 and alveolar to arterial gradient for O-2 levels were excellent throughout the 6-hour observation period, but in group 2 they progressively deteriorated. However, ultrafiltration significantly (P = .02) improved the PaO2 level in group 3. On histology, interstitial edema and polynuclear cell infiltration were most marked in group 2 and significantly worse than in groups 1 and 3. Myeloperoxidase assay and real-time quantitative reverse transcription-polymerase chain reaction showed increased myeloperoxidase activity and interleukin 6 gene expression in group 2 grafts compared with group 1 grafts. Myeloperoxidase activity and interleukin 6 gene expression were suppressed with ultrafiltration.
Conclusions: Cardiopulmonary bypass had negative effects on the graft, but ultrafiltration attenuated acute lung dysfunction by reducing the inflammatory response.

DOI： 10.1016/j.jtcvs.2006.08.020

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: An earthquake measuring 6.8 on the Richter scale struck the Niigata-Chuetsu region of Japan at 5.56 P. M. on the 23rd of October, 2004. The earthquake was followed by sustained occurrence of numerous aftershocks, which delayed reconstruction of community lifelines. Even one year after the earthquake, 9,160 people were living in temporary housing. Such a devastating earthquake and life after the earthquake in an unfamiliar environment should cause psychological distress, especially among the elderly.
Methods: Psychological distress was measured using the 12-item General Health Questionnaire (GHQ-12) in 2,083 subjects (69% response rate) who were living in transient housing five months after the earthquake. GHQ-12 was scored using the original method, Likert scoring and corrected method. The subjects were asked to assess their psychological status before the earthquake, their psychological status at the most stressful time after the earthquake and their psychological status at five months after the earthquake. Exploratory and confirmatory factor analysis was used to reveal the factor structure of GHQ12. Multiple regression analysis was performed to analyze the relationship between various background factors and GHQ-12 score and its subscale.
Results: GHQ-12 scores were significantly elevated at the most stressful time and they were significantly high even at five months after the earthquake. Factor analysis revealed that a model consisting of two factors ( social dysfunction and dysphoria) using corrected GHQ scoring showed a high level of goodness-of-fit. Multiple regression analysis revealed that age of subjects affected GHQ-12 scores. GHQ-12 score as well as its factor 'social dysfunction' scale were increased with increasing age of subjects at five months after the earthquake.
Conclusion: Impaired psychological recovery was observed even at five months after the Niigata-Chuetsu Earthquake in the elderly. The elderly were more affected by matters relating to coping with daily problems.

DOI： 10.1186/1471-2458-6-230

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：OXFORD UNIV PRESS  

The apolipoprotein E (APOE) gene has been consistently shown to be a major genetic risk factor; however, all cases of Alzheimer's disease (AD) cannot be attributed to the epsilon 4 variant of APOE, because about half of AD patients have the APOE-epsilon 3*3 genotype. To identify an additional genetic risk factor(s), we performed large-scale single nucleotide polymorphism (SNP)-based association analysis of 1526 late-onset AD patients and 1666 control subjects in a Japanese population. We prepared two independent sets consisting of exploratory and validation samples, respectively, with only the APOE-epsilon 3*3 genotype, and first carried out genotyping for the exploratory set with 1206 SNPs in the region between 60 and 107 Mb on chromosome 10q that is implicated by linkage studies as containing an AD susceptibility locus. Thirty-five SNPs that showed significant values (P < 0.01) were followed-up to detect any association with the validation samples. Finally, six SNPs exhibited replicated significant associations (P=0.000035-0.00048) on meta-analysis of both sets. These SNPs were clustered in a locus spanning 220 kb at genomic position 101 Mb, and three of the six SNPs were located in the dynamin-binding protein (DNMBP) gene. Quantitative real-time RT-PCR analysis demonstrated that neuropathologically confirmed AD brains exhibit a significant reduction of DNMBP mRNA compared with age-matched ones (P < 0.0169). Thus, we confirmed the association of DNMBP with AD individuals with the APOE-epsilon 3*3 genotype or lacking the epsilon 4 allele, and DNMBP may be one of the susceptibility genes for AD.

DOI： 10.1093/hmg/ddl142

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Hospital length of stay (LOS) of Japanese inpatients is extraordinarily long, partly because of the nature of the health insurance system in Japan. We investigated factors that affect the LOS in Japan, taking pediatric nephrosis as an example. The characteristics of 78 hospitalized children with steroid-sensitive nephrotic syndrome were studied. The median LOS of the patients was 47 days. Most of the patients' mothers (92.3%) stayed in hospital during admission to care for their children. Using multivariate Cox's regression analysis with time-dependent covariates, non-working mother and smaller number of siblings were found to be factors significantly associated with prolonged LOS. These factors are presumed to allow the mothers to care for their hospitalized children for a long period. No medical or clinical factors played a significant role in the prolonged LOS. These results suggest that sociocultural factors have a greater influence on the LOS in Japan than do medical factors such as disease course, coexisting illness, complications, and treatment response. © 2005 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.healthpol.2005.06.008

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS AS  

DOI： 10.1080/08035250500411957

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To realize an effective cost control, a practical and accurate cost accounting system is indispensable in hospitals. In traditional cost accounting systems, the volume-based costing (VBC) is the most popular cost accounting method. In this method, the indirect costs are allocated to each cost object (services or units of a hospital) using a single indicator named a cost driver (e.g., Labor hours, revenues or the number of patients). However, this method often results in rough and inaccurate results. The activity based costing (ABC) method introduced in the mid 1990s can prove more accurate results. With the ABC method, all events or transactions that cause costs are recognized as "activities", and a specific cost driver is prepared for each activity. Finally, the costs of activities are allocated to cost objects by the corresponding cost driver. However, it is much more complex and costly than other traditional cost accounting methods because the data collection for cost drivers is not always easy. In this study, we developed a simplified ABC (S-ABC) costing method to reduce the workload of ABC costing by reducing the number of cost drivers used in the ABC method. Using the S-ABC method, we estimated the cost of the laboratory tests, and as a result, similarly accurate results were obtained with the ABC method (largest difference was 2.64%). Simultaneously, this new method reduces the seven cost drivers used in the ABC method to four. Moreover, we performed an evaluation using other sample data from physiological laboratory department to certify the effectiveness of this new method. In conclusion, the S-ABC method provides two advantages in comparison to the VBC and ABC methods: (1) it can obtain accurate results, and (2) it is simpler to perform. Once we reduce the number of cost drivers by applying the proposed S-ABC method to the data for the ABC method, we can easily perform the cost accounting using few cost drivers after the second round of costing. © 2006 Tohoku University Medical Press.

DOI： 10.1620/tjem.208.213

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：BIOMED CENTRAL LTD  

Background: In Japan, all citizens are covered by the national insurance system in which universal free access to healthcare services is promised to everybody. There are no general physicians or gatekeepers in the Japanese healthcare system.
Methods: We studied the pattern of referral of inpatients from secondary care hospitals to a tertiary care university hospital and the reverse referral under the situations using a geographic information system (GIS), taking paediatric inpatients as an example.
Results: The results showed that 61.2% of the patients were directly admitted to the hospital without referral from other hospitals or clinics and that 82.8% of the inpatients were referred to the outpatient department of the hospital to which they had been admitted. GIS analysis for the inpatients service area showed the hospital functions as both a secondary care hospital and tertiary care hospital. Patients who lived near the hospital tended to be admitted directly to the hospital, and patients who lived far from the hospital tended to utilize the hospital as a tertiary care provider. There were territorial disputes with other secondary care hospitals. To estimate spatial differences in referral to aftercare, we analyzed the spatial distribution of inpatients with focus on their length of hospital stay (LOS). GIS analysis revealed apparent foci of patients with long LOS and those with low LOS.
Conclusion: These results suggest that the function of university hospital in Japan is unspecialized and that the referral route from the university hospital to aftercare is also unequipped.

DOI： 10.1186/1472-6963-6-11

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：KARGER  

Background and Objectives: Because inhaled corticosteroids (ICS) play a central role in the management of asthma, new drug delivery systems for fluticasone propionate, Diskhaler (FPdh) and Diskus (FPdk), were developed. However, few studies have focused on compliance with these drug delivery systems, which can influence drug efficacy. Hence, we compared compliance with FPdk versus that with FPdh. Methods: Data were obtained from a survey of pharmacists dispensing anti-asthmatic drugs to adult asthma patients who visited participating pharmacies between October 2002 and November 2003. Patients were limited to regular users of FPdh or FPdk whose medication and daily administration frequency of ICS were evaluated on the basis of pharmaceutical records. Data on asthma status and various other factors affecting ICS compliance were obtained by questionnaire. Results: Data were acquired on 337 patients. There were no significant differences in gender, age, and duration between the FPdk and FPdh groups. Although FPdk compliance was significantly higher than that of FPdh, conversely there was no significant difference in daily dose and administration frequency between the 2 groups. Furthermore, there was no significant difference in the rate of concomitant drug and in various influencing factors associated with drug compliance. Regarding compliance of concomitant drug, that of oral sustained-released theophylline was significantly lower in FPdk versus FPdh users. Conclusion: In the area of drug compliance, FPdk is superior to FPdh. Although the reason for this is unclear, it is probably due to the characteristics of FPdk itself. Copyright (C) 2006 S. Karger AG, Basel.

DOI： 10.1159/000095313

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japan Atherosclerosis Society  

To investigate risk factors for coronary artery disease (CAD), we analyzed the clinical parameters of patients with a coronary artery bypass graft (CABG) in a case-control study. Eighty-eight patients (75 males and 13 females) who underwent CABG surgery between 2001 and 2002 were compared with age- and sex-matched healthy controls randomly chosen from the registry of Kobari Health Care Center. Wilcoxon's signed rank test and McNemar's test were used for pairwise comparisons. Multivariate logistic regression analysis was used to identify significant risk factors for CABG. Significant differences between the patients and controls were observed in HDL-C (p &lt
0.001), HbA1c (p &lt
0.001), Brinkman Index (BI
p &lt
0.001), body mass index (BMI
p = 0.002), and systolic blood pressure (SBP
p = 0.013). Subjects with an abnormal BMI, HbA1c, or HDL-C or high BI value made up a significantly higher proportion of the patients who underwent CABG, compared to their age- and sex-matched controls. Multivariate logistic regression analysis identified high levels of HbA1c, low levels of HDL-C, and high scores on the BI as significant risk factors for needing a CABG. These results demonstrate that, despite the modification of laboratory determinations by antecedent treatment, HDL-C, HbA1c, BI, BMI, and SBP are significant indicators of risk for CAD.

DOI： 10.5551/jat.13.62

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN  

Objectives. Activity-based costing (ABC) is widely used to precisely allocate indirect costs to medical services. In the ABC method, the indirect cost is divided among the medical services in proportion to the volume of cost drivers", for example, labor hours and the number of hours of surgery. However, the workload of data collection of cost drivers can be time-consuming and a considerable burden if there are many cost drivers. The authors aim to develop a method for objectively reducing the cost drivers used in the ABC method.
Methods. In the ABC method, the cost driver is assigned for each activity. We assume that these activities and cost drivers are the best combination. Our method, that is cost driver reduction (CDR), can objectively select surrogates of the cost drivers for each activity in ABC from candidate cost drivers. Concretely, the total indirect cost of an activity is temporarily allocated to the medical services using each candidate of cost drivers. The difference between the costs calculated by each candidate and the proper cost driver used in ABC is calculated to evaluate the similarity by the evaluation function.
Results: We estimated the cost of laboratory tests using our method and revealed that the number of cost drivers could be reduced from seven in the ABC to four. Similarly, the results of cost estimation obtained by our method were as accurate as those calculated using the ABC.
Conclusions: Our method provides two advantages compared to the ABC method: 1) it provides results that are as accurate as those of the ABC method, and 2) it is simpler to perform complicated estimation of hospital costs.

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Background and Objectives: Because inhaled corticosteroids (ICS) play a central role in the management of asthma, new drug delivery systems for fluticasone propionate, Diskhaler (FPdh) and Diskus (FPdk), were developed. However, few studies have focused on compliance with these drug delivery systems, which can influence drug efficacy. Hence, we compared compliance with FPdk versus that with FPdh. Methods: Data were obtained from a survey of pharmacists dispensing anti-asthmatic drugs to adult asthma patients who visited participating pharmacies between October 2002 and November 2003. Patients were limited to regular users of FPdh or FPdk whose medication and daily administration frequency of ICS were evaluated on the basis of pharmaceutical records. Data on asthma status and various other factors affecting ICS compliance were obtained by questionnaire. Results: Data were acquired on 337 patients. There were no significant differences in gender, age, and duration between the FPdk and FPdh groups. Although FPdk compliance was significantly higher than that of FPdh, conversely there was no significant difference in daily dose and administration frequency between the 2 groups. Furthermore, there was no significant difference in the rate of concomitant drug and in various influencing factors associated with drug compliance. Regarding compliance of concomitant drug, that of oral sustained-released theophylline was significantly lower in FPdk versus FPdh users. Conclusion: In the area of drug compliance, FPdk is superior to FPdh. Although the reason for this is unclear, it is probably due to the characteristics of FPdk itself. Copyright (C) 2006 S. Karger AG, Basel.

DOI： 10.1159/000095313

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DOI： 10.2332/allergolint.54.401

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A prospective payment system based on diagnosis procedure combination (DPC/PPS) was introduced to acute care hospitals in Japan in April 2003. In order to increase hospital income, hospitals must shorten the average Length of stay (ALOS) and increase the number of patients. We constructed a simulation program for evaluating the relationships among ALOS, bed occupation rate (BOR) and hospital income of hospitals in which DPC/PPS has been introduced. This program can precisely evaluate the hospital income by regulating the ALOS and the number of patients for each DPC. By using this program, it is possible to predict the optimum ALOS and optimum number of inpatients for each DPC in order to increase hospital income. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.cmpb.2005.09.003

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Concanavarin-A (conA)-stimulated peripheral blood mononuclear cells (PBMNC) from patients with idiopathic nephrotic syndrome (INS) produce putative factors that increase vascular permeability. These factors are expressed in the nephrotic phase but are reduced in the convalescent phase. To identify the genes that are expressed only in the nephrotic phase, we performed cDNA subtraction using conA-stimulated PBMNC from three patients with INS. We isolated several gene transcripts in all three subtracted cDNA libraries. Among these genes, IgE-dependent histamine-releasing factor (HRF) was overexpressed in the nephrotic phase not only at the mRNA level but also at the protein level in another 10 patients with INS. Moreover, we found increased secretion of HRF from conA-stimulated PBMNC in the nephrotic phase. The results suggest that HRF is involved in the pathogenesis of idiopathic nephrotic syndrome.

DOI： 10.1111/j.1365-2249.2005.02890.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

We have constructed a database system named CHRONIS (CHROmosome and Nano-Information System) to collect images of animal chromosomes and related nanotechnological information. CHRONIS enables rapid sharing of information on chromosome research among cell biologists and researchers in other fields via the Internet. CHRONIS is also intended to serve as a liaison tool for researchers who work in different centers. The image database contains more than 3000 color microscopic images, including karyotypic images obtained from more than 1000 species of animals. Researchers can browse the contents of the database using a usual World Wide Web interface in the following URL: http://chromosome.med.niigata-u.ac.jp/chronis/chronisservlet/. The system enables users to input new images into the database, to locate images of interest by keyword searches, and to display the images with detailed information. CHRONIS has a wide range of applications, such as searching for appropriate probes for fluorescent in situ hybridization, comparing various kinds of microscopic images of a single species, and finding researchers working in the same field of interest.

DOI： 10.1007/s10577-005-0985-6

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It is difficult to estimate precisely the costs of disposable materials used during surgical operations. To evaluate the actual costs of disposable materials, we calculated the actual costs of disposable materials used in 59 operations by taking account of costs of all disposable materials used for each operation. The costs of the disposable materials varied significantly from operation to operation (US$ 38-4230 per operation), and the median [25-percentile and 75-percentile] of the sum total of disposable material costs of a single operation was found to be US$ 686 [205 and 993]. Multiple regression analysis with a stepwise regression method showed that costs of disposable materials significantly correlated only with operation time (p < 0.001). Based on the results, we propose a simple method for estimating costs of disposable materials by measuring operation time, and we found that the method gives reliable results. Since costs of disposable materials used during surgical operations are considerable, precise estimation of the costs is essential for hospital cost accounting. Our method should be useful for planning hospital administration strategies. (c) 2004 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.healthpol.2004.10.003

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DOI： 10.1111/j.1440-1754.2005.00644_1.x

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Idiopathic nephrotic syndrome is the most common form of nephrotic syndrome in children, but little is known about the etiology of the disease. To obtain new insights into the etiology of the disease, we studied circannual patterns of initial episodes and relapses of steroid-sensitive nephrotic syndrome (SSNS). From 1986 to 2003, there were 45 children with SSNS in our hospital, and they experienced 43 relapses during that period. Initial episodes of SSNS were found to show significant circannual variation with an autumn peak both by Rogers test and Freedmans test, and the circannual pattern was more obvious in patients with high serum IgE levels. Chronological evaluation by means of Fourier analysis showed a clear circannual pattern. In contrast, relapses of SSNS showed circannual variation with a spring peak, which was a result of a high frequency of relapses after upper respiratory infections in January. These results suggest that circannual variation in initial episodes of SSNS might be associated with allergic predisposition, whereas circannual variation in relapses might be associated with preceding upper respiratory infections.

DOI： 10.1007/s00467-004-1780-x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Allergology  

Background: Because bronchial inflammation was recognized as a basic component of bronchial asthma, the strategy for asthma management has changed in the last two decades. In Japan there are few clinico-epidemiological reports of changes in the management of bronchial asthma in actual practice. In this study, we analyzed practical asthma management in Japan, and examined changes in the prevalence of asthma medication and relation between these changes and the level of asthma control and management. Methods: From 1998 to 2002, questionnaires on asthma control, asthma related emergent episodes and satisfaction in daily life. Questionnaires were distributed to adult asthmatic patients. Questionnaires about the patients' profiles and medication were also given to the patients' doctors. Results: The total number of patient responders was approximately 2500-3300 per year. The rate of peak flow meter (PEFM) use was under approximately only 40% and plateaued from 2000 to 2002. The percentage of inhaled corticosteroid use and leukotriene receptor antagonist use increased, from 62.0%, 27.2% to 77.4%, 40.6% respectively. Indicators for asthma control, including presence of attacks and sleep disturbance, were significantly improved. Limited to PEFM users, there was an improvement hospitalization, ambulance use or ED visits and in satisfaction in daily life based on a Quality of Life (QOL) indicator. Conclusions: These results indicate that the prevalence of anti-inflammatory agents, including inhaled corticosteroids and leukotriene receptor antagonist, was associated with an adequate improvement in asthma control in clinical practice. In asthma management in clinical practice, prevalence of PEFM may play an important role in the improvement of asthma related emergent episodes or QOL. ©2005 Japanese Society of Allergology.

DOI： 10.2332/allergolint.54.555

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society of Allergology  

Background: Not only monotherapy with inhaled corticosteroids (ICS) but also the concurrent use of other antiasthmatic agents, including leukotriene receptor antagonists (LTRA), play an important role in the management of asthma. However, few studies have focused on compliance with these drugs and on the relation between drug compliance and drug usage. Methods: Data were derived from a survey of pharmacists dispensing antiasthmatic drugs to adults with asthma who visited participating pharmacies from October through November 2002. The patients were limited to regular users of ICS whose medication had not been changed for at least 6 months before the survey. Drug compliance and the daily administration frequency of antiasthmatic agents were evaluated on the basis of pharmaceutical records. Results: Completed data were received for 322 patients. ICS compliance was lower than compliance with oral sustained-released theophylline (OSRT) and compliance with LTRA. ICS compliance significantly correlated with OSRT compliance and with LTRA compliance. There were no significant differences of ICS compliance among ICS alone, ICS + LTRA, ICS + OSRT and ICS + LTRA + OSRT group, while the daily inhalation frequency in ICS + OSRT or ICS + OSRT + LTRA group were higher than those in ICS alone group. Although there was a significant negative correlation between ICS compliance and daily inhalation frequency, neither OSRT compliance nor LTRA compliance significantly correlated with the tablet or capsule numbers per day. These findings indicate that OSRT may increase the compliance of concomitant ICS, and that the compliance of OSRT or LTRA is independent of the numbers of tablets taken per day. Conclusions: These unique characteristics should be considered in the treatment and guidance of patients with bronchial asthma. ©2005 Japanese Society of Allergology.

DOI： 10.2332/allergolint.54.547

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DOI： 10.14442/general2000.5.7

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD  

Decreased numbers of natural killer (NK) cells and impaired NK function have been reported in patients with systemic lupus erythematosus (SLE). Since DAP12 plays a pivotal role in activation of NK cells, we analyzed the expressions of DAP12 protein and mRNA in peripheral blood NK cells from patients with SLE. Both DAP12 protein and mRNA expressions in NK cells from the SLE patients were decreased compared with those in NK cells from normal subjects. Sequence analysis of DAP12 cDNA showed increased nucleotide mutations, including both nucleotide substitutions and deletions. In spite of the mRNA mutations, we found no mutations in genomic DNA, suggesting that mRNA was modified during or after transcription. Decreased expression of DAP12 in NK cells from the patients was accompanied by increased expression of ADAR1 (adenosine deaminase that acts on RNA transcripts) and by decreased expression of NKp44. These results suggest that abnormal expression of DAP 12 molecules in NK cells may account for the impairment of NK cell function in patients with SLE. (C) 2004 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.jaut.2004.09.003

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DOI： 10.11477/mf.1686100473

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Moving picture expert group compression standard version 4 (MPEG-4) is a standard for video coding aimed at multimedia applications. MPEG-4 was developed to enable high compression rate in a low bitrate transmission via the Internet or mobile telecommunications. Although these characteristics of MPEG-4 are suitable for tetemedicine, little is known about the possibility of using this technology in the field of telemedicine. We evaluated the quality of MPEG-4-encoded medical video streams and compared them with original analogue videos and audio-video-interleave (AVI) files. Although MPEG-4 video streams have the advantage of small file size, they were found to be inferior to original videos and AVI files in terms of smoothness of motion pictures, sharpness of images and clearness of sound. Illegibility of characters was a major probelem in MPEG-4 files. The score for total impression of MPEG-4 files was significantly lower than those for AVI files. The results of this study suggest that the quality of MPEG-4-encoded video streams is not adequate for telemedicine. (C) 2004 Elsevier Ireland Ltd. All rights reserved.

DOI： 10.1016/j.cmpb.2004.03.002

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing Inc.  

Background. Glomerular accumulation of leukocytes, including lymphocytes, is a common feature in most types of glomerulonephritis. However, the role of lymphocytes in progressive glomerulonephritis has not been elucidated. We examined the role of lymphocytes in the development of progressive mesangial proliferative glomerulonephritis induced by two injections of monoclonal antibody 1-22-3 in rats. Methods. To elucidate the role of lymphocytes, circulating lymphocytes were depleted using specific monoclonal antibodies to rat lymphocytes prior to the induction of progressive glomerulonephritis. The effects of lymphocyte depletion on proteinuria and glomerular alterations were assessed 7 and 56 days after the induction of progressive glomerulonephritis. Results. Significant glomerular accumulation of CD4+ T cells, CD8+ T cells, and ED3+-activated macrophage were observed after the induction of glomerulonephritis. Depletion studies showed that continuous treatment with anti-CD5, anti-CD4, or anti-CD8 treatment reduced proteinuria and ameliorated the glomerular lesions on day 56. Depletion of CD4+ T cells also reduced glomerular accumulation of CD8+ T cells and ED3+-activated macrophages, and reduced glomerular expression of mRNA for interferon-gamma (INF-γ) (63.0% in anti-CD5 and 62.3% reduction in anti-CD4). Transit lymphocyte depletion limited in early stage of progressive glomerulonephritis demonstrated that CD4+ T-cell depletion, but not anti-CD8 treatment prevented glomerular injuries 56 days after the induction of progressive glomerulonephritis. Conclusion. CD4+ T cells played a central role in the development of progressive glomerulonephritis, controlling recruitment and activation of CD8+ cytotoxic cells and/or macrophages.

DOI： 10.1111/j.1523-1755.2004.00852.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC MEDICINE PRESS LTD  

We developed a teleradiology system linking a general hospital on Sado Island to tertiary care hospitals in Niigata City. The island is 40 km from Niigata City on the mainland and has only one diagnostic radiologist (for 72,000 islanders). Fibre optic cables between Sado Island and Niigata City were used for transmission. The introduction of the teleradiology system facilitated diagnostic and therapeutic consultation with specialists in Niigata City. The performance of the system was evaluated (on a scale of 0-6, with higher scores indicating better performance) by five diagnostic radiologists, who rated 32 features of the system twice, once in April 2002 and once in September 2003. The performance ratings improved from 1.38 to 2.86. While many of the initial problems with the software had been resolved, many still remained.

DOI： 10.1258/1357633041424430

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DOI： 10.1007/s00431-003-1325-5

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Recent studies have suggested that a high percentage of Epstein-Barr virus (EBV)-infected lymphocytes in peripheral blood of patients with chronic, active EBV infection (CAEBV) is of T cell origin. Although T cells are expanded oligoclonally in CAEBV, it is not clear whether the restricted diversity of T cells arise from immune reaction against EBV-related antigens or from proliferation of EBV-infected cells. We experienced a patient with CAEBV who had biclonal expansion of peripheral blood T cells. We identified clonotypes of these two T cell clones in detail and purified the T cell clones. EBV infected mainly the two T cell clones, whereas the viral loads in peripheral blood cells other than these T cell clones were low or undetectable. The EBV strains infecting the two T cells clones were indistinguishable from each other by a series of genotype analyses of the virus. These results suggest that the two T cell clones infected with the same monoclonal EBV proliferated in peripheral blood of the patient.

DOI： 10.1046/j.1365-2249.2003.02270.x

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Immunological states during human malarial infection were examined. In parallel with parasitemia and anemia, granulocytosis was induced in the blood of patients, especially those infected with Plasmodium (P.) falciparum. At that time, the level of lymphocytes remained unchanged or slightly increased in the blood. However, the distribution of lymphocyte subsets was modulated, showing that the proportion of CD56+T cells, CD57+T cells, and γδT cells (i.e. all unconventional T cells) had increased in patients infected with P. falciparum or P. vivax. This phenomenon occurred at the early phase of infection and disappeared in the course of recovery. The data from patients with multiple attacks of P. vivax infection showed that there was no augmentation of these responses. In adult cases, the increase in the proportion of unconventional T cells seemed to closely parallel disease severity. However, all these responses were weak in children, even those infected with P. falciparum. In conjunction with accumulating evidence from mouse malaria experiments, the present results suggest that the immunological state induced by malarial infection might mainly be an event of unconventional T cells and that the immunological memory might not be long-lasting, possibly due to the properties of unconventional T cells. © 2002 Elsevier Science Ireland Ltd. All rights reserved.

DOI： 10.1016/S1383-5769(02)00085-5

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A 9-month-old boy presented with chronic arteritis of the aorta and its major branches. The clinical manifestations at onset of his illness were compatible with those of Kawasaki syndrome. However, the febrile period lasted for 2 months despite various immunosuppressive therapies, and the levels of C-reactive protein remain high 18 months after onset. Elevated circulating immune complexes, decreased serum complement levels, hypergammaglobulinaemia and monoclonal gammopathy were observed. Active HHV-6 infection was shown by increased serum levels of antihuman herpesvirus-6 (HHV-6) IgG and IgM antibodies, and positive HHV-6 DNA in sera, peripheral blood mononuclear cells (PBMNC) and lymph nodes. HHV-6 was actively replicating in PBMNC and lymph nodes, as shown by the detection of transcripts for the virus structural antigen. These results suggest that large vessel arteritis can be associated with HHV-6 infection.

DOI： 10.1007/s100670200129

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Publishing  

Background: There has recently been an accumulation of evidence suggesting that endothelial cells (EC) play a crucial role in the pathogenesis of bronchial asthma. We examined the prevalence and isotypes of anti-EC antibodies (AECA) in the sera of children with asthma and determined the antigenic targets associated with AECA reactivity. Methods: Levels of each class of AECA were determined by cellular ELISA in 156 children with asthma and in 203 control children. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and western blot analysis were performed in samples that contained high levels of AECA. Results: In the cellular ELISA, the IgE class of AECA was detected significantly more frequently in children with asthma (25/156
16.0%) than in healthy controls (2/203
1.0%
P &lt
0.01). There were no differences in the frequencies of detection of IgG, IgA and IgM classes of AECA between patients and controls. The IgE-AECA was more frequently detected in younger children (23/69 vs 2/87 for children younger and older than 4 years of age, respectively). There was no correlation between the level of IgE-AECA and that of total IgE or house dust mite-specific IgE. In western blot analysis, IgE antibodies against a component of EC with a molecular mass of 75 kDa were detected in 20 of 25 patients (80.0%) positive for IgE-AECA, but they were less frequently detected in patients negative for IgE-AECA (2/34 (5.9%)
P &lt
0.01). Conclusions: These results demonstrate that a small fraction of asthmatic children has IgE-AECA and that the antigenic target of IgE-AECA is a component of the EC with a molecular weight of 75 kDa.

DOI： 10.1046/j.1440-1592.2002.00253.x

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The aetiology of IgA nephropathy (IgAN) is closely related with abnormality of mucosal immunity. We investigated the roles of γδ T cells in the regulation of IgA production by B cells in IgAN patients. The proportion of γδ T cells in peripheral blood mononuclear cells (PBMNC) was higher in IgAN patients than in the controls and was found to be correlated with the proportion of surface IgA-positive (sIgA+) B cells, which are precursors of IgA-secreting plasma cells. After in vitro PWM stimulation, sIgA expression on B cells and IgA production were significantly enhanced in PBMNC obtained from IgAN patients, whereas the enhancements were abolished by removal of γδ T cells from the PBMNC. Purified γδ T cells from IgAN patients induced surface IgA expression on naïve sIgD+ B cells more effectively than did αβ T cells. Moreover, stimulated γδ T cells from IgAN patients produced a larger amount of TGF-β1, which is one of the main cytokines that induces IgA class switching on B cells, as compared with αβ T cells and control γδ T cells. The expanded γδ T cells from IgAN patients exclusively expressed Vγ9, and the nucleotide sequences of junctional regions of Vγ9 showed very limited TCR diversities. It was therefore concluded that γδ T cells, which are expanded in response to specific antigens, enhance IgA class switching on B cells in IgAN patients.

DOI： 10.1046/j.1365-2249.2001.01494.x

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ZAP-70 deficiency is a rare primary immunodeficiency characterized by the absence of peripheral CD8+ T cells and defects in T-cell receptor (TCR) signalling. T cells in ZAP-70-deficient patients are assumed to have no helper functions for B-cell immunoglobulin synthesis, whereas the patients rarely have antigen-specific antibodies. We experienced a ZAP-70-deficient patient, who had immunoglobulin E (IgE) antibodies specific to food allergens, and we investigated the mechanisms of switching to IgE in the patient. Peripheral blood mononuclear cells from the patient did not proliferate upon stimulation with the antigens but produced distinct levels of interleukin-4 (IL-4). Cell sorting analysis indicated that the cells that produced IL-4 in response to the antigens were enriched in CD4+ T cells. Purified CD4+ T cells from the patient produced IL-4 and expressed CD40L upon stimulation with anti-CD3. Moreover, CD4+ T cells pretreated with anti-CD3 induced mature ε transcript on naive B cells. Since the results indicated that there remained sufficient T-cell receptor (TCR)-signalling in the patient's T cells to exert antigen-specific IgE switching on B cells, we next investigated the expression of the ZAP-70-homologous kinase Syk. Syk was present in high levels in patient's CD4+ T cells and was tyrosine-phosphorylated after TCR stimulation. Inhibition of Syk by piceatannol resulted in decreased production of IL-4 and expression of CD40L on patient's CD4+ T cells. Moreover, Syk was expressed on all human T-cell leukaemia virus (HTLV-1)-transformed T-cell lines derived from peripheral blood of the patient, whereas it was low or undetectable in control lines. It was therefore concluded that specific IgE responses in the patient were most likely to be mediated by Syk-dependent TCR-signalling.

DOI： 10.1046/j.1365-2567.2001.01246.x

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Many clinicians have believed that H2-blockers and proton pump inhibitors ameliorate gastric ulcers via their antacid function. We examined the effects of these antacids on granulocytes. Gastric ulcer patients were administered an H2-blocker or proton pump inhibitor for a week and the number of granulocytes and the superoxide production were examined. To determine the trafficking of granulocytes, mice were exposed to restraint stress for 24 hr. The H2-blocker decreased the number of granulocytes, while the proton pump inhibitor suppressed their superoxide production in humans and mice. The major function of H2-blockers and proton pump inhibitors in curing gastric ulcers seems to be their suppressive effects on granulocytes. In this case, stress accelerates the trafficking of granulocytes from the bone marrow to the gastric mucosa. If we demonstrate a role for granulocytes in gastric ulcer formation, an gap in the acid-pepsin theory and the Helicobacter pylori theory is filled in.

DOI： 10.1023/A:1005526126694

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Background: Increased numbers of lymphocytes have been identified in biopsy specimens of human mesangial proliferative glomerulonephritis (GN). However, the causal relationship between infiltrating T lymphocytes and mesangial changes in mesangial proliferative GN has not been previously evaluated. In this study, we elucidated the role of lymphocytes in the development of mesangial proliferative GN. Method: Immunohistological and flow cytometric analyses as well as a reverse transcription-polymerase chain reaction (RTPCR) studies were performed in monoclonal antibody (mAb) 1-22-3- induced Thy 1.1 GN. To elucidate the role of these lymphocytes, depletion studies were carried out using anti-CD8 mAb (OX-8), which depletes both CD8+ T lymphocytes and natural killer (NK) cells and anti-CD5 mAb (OX-19), which depletes both CD4+ and CD8+ T lymphocytes. Results: Immunofluorescence (IF) studies revealed that NK cells and CD4+ T lymphocytes were recruited into glomeruli. Glomerular mRNA expression for interferon-γ interleukin-2 (IL-2), IL-10, and perforin increased after induction of GN. Increased expressions of several chemokines, which have the potential to attract lymphocytes, were also detected. Anti-CD8 mAb treatment completely prevented the recruitment of NK cells: however, it had no protective effect on proteinuria and mesangial injury. By contrast, anti-CD5 mAb treatment suppressed the recruitment of CD4+ T lymphocytes into glomeruli and reduced proteinuria (60.4 ± 25.7 vs. 120.0 ± 32.3 mg/day, P &lt
0.05) and mesangial changes evaluated by total number of cells in glomeruli (63.2 ± 6.0 vs. 81.4 ± 5.9, P &lt
0.01) and α- smooth muscle actin staining score (1.4 ± 0.2 vs. 2.2 ± 0.4, P &lt
0.01) on day 14 after induction of GN. mRNA expression for IL-2 was significantly reduced by OX-19 treatment. Conclusion: T lymphocytes participate in the development of mesangial proliferative GN.

DOI： 10.1046/j.1523-1755.2000.00145.x

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Blackwell Munksgaard  

Background/Aims: Liver natural killer 1.1 antigen (NK1)+T cells and IL- 4 play a crucial role in concanavalin-A (Con-A)-induced hepatic injury in mice, and a T helper (Th) 2 immune response was thus suggested to be involved. This study was designed to examine the effect of bacterial lipopolysaccharide (LPS), a strong inducer of a Th 1 immune response, on Con- A hepatic injury and also to clarify further the cytokine milieu of Con-A hepatitis. Methods: LPS were injected into mice before Con-A injection to evaluate the effect on hepatic injury. The effect of the pretreatment with various T1 and Th2 cytokines or anti-cytokine antibodies on Con-A hepatitis was also examined. Results: LPS in quantities ≥500 ng/mouse, when injected 24 h before Con-A injection, abrogated the Con-A-induced elevation of transaminases, hepatocyte destruction and serum 11,-4 elevation. This LPS inhibitory effect was blocked when the mice were injected with either anti- IL-6 antibody before LPS injection or IL-4 before Con-A injection. IL-6, but neither IL-10 nor IL-12 pretreatment suppressed Con-A-induced IL-4 production and hepatitis. NK1+ T cells produced IL-4 while both NK1+ T cells and NK1- T cells produced IFN-γ. Not only anti-IL-4 antibody but also the anti-IFN- γ antibody pretreatment inhibited Con-A hepatitis. However, although the anti-IL-4 antibody suppressed IL-4 alone, the anti-IFN-γ Ab unexpectedly inhibited both IFN-γ and IL-4 elevation, while IL-4 injection evoked a moderate Con-A hepatitis even in the anti-IFN-γ antibody-treated mice. Furthermore, the IL-4 mutant mice did not develop Con-A hepatitis. Conclusion: LPS inhibited Con-A hepatitis by inducing IL-6 and thereby inhibited IL-4 synthesis from NK1+ T cells. Although both IL-4 and IFN-γ were required for the full induction of Con-A hepatic injury, exogenous IL-4 evoked a moderate Con-A hepatitis, even in the absence of IFN-γ.

DOI： 10.1016/S0168-8278(99)80159-7

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Language：Japanese   Publishing type：Research paper (scientific journal)  

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In a recent series of studies, we demonstrated that stress in humans and animals, with resultant sympathetic nerve strain, induces severe granulocytosis, because granulocytes carry adrenergic receptors on the surface. Because activated granulocytes produce free radicals and superoxides, they sometimes induce tissue damage if the stress is too strong or continuous. Human neonates are also known to show high levels of granulocytes in the peripheral blood. In this study, we investigated whether such neonatal granulocytosis are a stress-associated response at birth. Both human and mouse materials, before and after birth, were used. The number of leukocytes in the blood, as well as some other factors in the serum, were measured. Although levels of granulocytes were found to be low in fetal humans and mice, they increased sharply after birth. In parallel with this postpartal granulocytosis, transaminases in sera increased transiently. In reference to results of a transient elevation in the levels of catecholamines at birth in mice, all these phenomena resemble stress-associated responses. Indeed, fatty liver and hematopoietic destruction in the liver were also observed in mice and humans. At this time, the production of inducible nitric oxide synthase (iNOS) by granulocytes in the liver was evident. These results suggest that neonatal granulocytosis is a postpartum event which results from various stresses (e.g., oxygen stress) at birth. This event may be responsible for such well-known neonatal phenomena as the termination of fetal hematopoiesis in the liver and as neonatal jaundice.

DOI： 10.1053/jhep.1997.v26.pm0009397999

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There are physiological variations in the levels of leucocytes. Among these, the circadian rhythm is very important in terms of the magnitude. Since newly identified lymphocyte subsets (i.e. extrathymic T cells) have recently been detected, a comprehensive study of the circadian rhythm was conducted. All leucocytes were found to vary in number or proportion with a circadian rhythm and were classified into two groups. One group--granulocytes, macrophages, natural killer (NK) cells, extrathymic T cells, gamma delta T cells, and CD8(+) subset--showed an increase in the daytime (i.e. daytime rhythm). The other group-T cells, B cells, alpha beta T cells, and CD4(+) subset--showed an increase at night. Humans are active and show sympathetic nerve dominance in the daytime. Interestingly, granulocytes and lymphocyte subsets with the daytime rhythm were found to carry a high density of adrenergic receptors. On the other hand, lymphocyte subsets with the night rhythm carried a high proportion of cholinergic receptors. Reflecting this situation, exercise prominently increased the number of cells with the daytime rhythm. These results suggest that the levels of leucocytes may be under the regulation of the autonomic nervous system.

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The existence of nicotinic acetylcholine receptors (nAChR) on lymphocytes remains controversial. We attempted to show the existence of nAChR on murine lymphocytes. The intraperitoneal injection of nicotine induced the lymphocytosis in the spleen on day 3. Although freshly isolated lymphocytes bound small quantities of fluorescein isothiocyanate (FITC)- conjugated α-bungarotoxin (αBuTx), they began to bind αBuTx after incubation in medium. In contrast to granulocytes, various lymphocyte subsets obtained from various lymphoid organs were found to bind αBuTx. Affinity purification of αBuTx-binding protein revealed that lymphocytes expressed the same nAChR molecules as those of muscle. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis showed that lymphocytes expressed the α-subunit mRNA of nAChR. These results suggest that lymphocytes carry nAChR on the surface and are stimulated directly via their nAChR by parasympathetic nerve stimuli.

DOI： 10.1046/j.1365-2567.1997.00323.x

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We analysed the biochemical features of receptors for the Fc-region of IgA (FcαR, CD89) on blood monocytes and granulocytes of patients with IgA nephropathy (IgAN). FcαR on monocytes of IgAN were found to have a higher Mr (60-80kD) than those of control monocytes (50-75kD) and granulocytes (55-75 kD) in both IgAN and controls as shown by immunoprecipitation analysis. Removal of N-linked carbohydrates from FcαR on monocytes of IgAN revealed a 32-36 kD protein core, the Mr of which was still higher than that of controls (28-32 kD). When FcαR transcripts were analysed by reverse-transcription- PCR only one prominent band was visualized in PCR products from IgAN monocytes. Since the results thus far show that IgAN monocytes express FcαR protein and mRNA differently from granulocytes and control monocytes, PCR products were then cloned and sequenced. The predominant band in PCR products from IgAN monocytes was identical to that of the FcαR a.1 transcript, and an additional 10 transcripts containing five novel transcripts were obtained, from granulocytes and control monocytes. In three transcripts we found an insertion sequence between the S2 and EC1 domains, suggesting the existence of a new exon. These results suggest a predominant usage of FcαR a.1 among various transcripts of FcαR in IgAN monocytes.

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Language：Japanese   Publishing type：Doctoral thesis  

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