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In urethra-sparing radiation therapy, prostatic urinary tract visualization is important in decreasing the urinary side effect. A methodology has been developed to visualize the prostatic urinary tract using post-urination magnetic resonance imaging (PU-MRI) without a urethral catheter. This study investigated whether the combination of PU-MRI and super-resolution (SR) deep learning models improves the visibility of the prostatic urinary tract. We enrolled 30 patients who had previously undergone real-time-image-gated spot scanning proton therapy by insertion of fiducial markers. PU-MRI was performed using a non-contrast high-resolution two-dimensional T2-weighted turbo spin-echo imaging sequence. Four different SR deep learning models were used: the enhanced deep SR network (EDSR), widely activated SR network (WDSR), SR generative adversarial network (SRGAN), and residual dense network (RDN). The complex wavelet structural similarity index measure (CW-SSIM) was used to quantitatively assess the performance of the proposed SR images compared to PU-MRI. Two radiation oncologists used a 1-to-5 scale to subjectively evaluate the visibility of the prostatic urinary tract. Cohen's weighted kappa (k) was used as a measure of agreement of inter-operator reliability. The mean CW-SSIM in EDSR, WDSR, SRGAN, and RDN was 99.86%, 99.89%, 99.30%, and 99.67%, respectively. The mean prostatic urinary tract visibility scores of the radiation oncologists were 3.70 and 3.53 for PU-MRI (k = 0.93), 3.67 and 2.70 for EDSR (k = 0.89), 3.70 and 2.73 for WDSR (k = 0.88), 3.67 and 2.73 for SRGAN (k = 0.88), and 4.37 and 3.73 for RDN (k = 0.93), respectively. The results suggest that SR images using RDN are similar to the original images, and the SR deep learning models subjectively improve the visibility of the prostatic urinary tract., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Yoshimura et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: The use of artificial intelligence (AI) in the medical industry promises many benefits, so AI has been introduced to medical practice primarily in developed countries. In Japan, the government is preparing for the rollout of AI in the medical industry. This rollout depends on doctors and the public accepting the technology. Therefore it is necessary to consider acceptance among doctors and among the public. However, little is known about the acceptance of AI in medicine in Japan., Objective: This study aimed to obtain detailed data on the acceptance of AI in medicine by comparing the acceptance among Japanese doctors with that among the Japanese public., Methods: We conducted an online survey, and the responses of doctors and members of the public were compared. AI in medicine was defined as the use of AI to determine diagnosis and treatment without requiring a doctor. A questionnaire was prepared referred to as the unified theory of acceptance and use of technology, a model of behavior toward new technologies. It comprises 20 items, and each item was rated on a five-point scale. Using this questionnaire, we conducted an online survey in 2018 among 399 doctors and 600 members of the public. The sample-wide responses were analyzed, and then the responses of the doctors were compared with those of the public using t tests., Results: Regarding the sample-wide responses (N=999), 653 (65.4%) of the respondents believed, in the future, AI in medicine would be necessary, whereas only 447 (44.7%) expressed an intention to use AI-driven medicine. Additionally, 730 (73.1%) believed that regulatory legislation was necessary, and 734 (73.5%) were concerned about where accountability lies. Regarding the comparison between doctors and the public, doctors (mean 3.43, SD 1.00) were more likely than members of the public (mean 3.23, SD 0.92) to express intention to use AI-driven medicine (P<.001), suggesting that optimism about AI in medicine is greater among doctors compared to the public., Conclusions: Many of the respondents were optimistic about the role of AI in medicine. However, when asked whether they would like to use AI-driven medicine, they tended to give a negative response. This trend suggests that concerns about the lack of regulation and about accountability hindered acceptance. Additionally, the results revealed that doctors were more enthusiastic than members of the public regarding AI-driven medicine. For the successful implementation of AI in medicine, it would be necessary to inform the public and doctors about the relevant laws and to take measures to remove their concerns about them., (©Honoka Tamori, Hiroko Yamashina, Masami Mukai, Yasuhiro Morii, Teppei Suzuki, Katsuhiko Ogasawara. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 16.03.2022.)

Background: An increasing number of people are visiting hospital websites to seek better services and treatments compared to the past. It is therefore important for hospitals to develop websites to meet the needs of their patients. However, few studies have investigated whether and how the current hospital websites meet the patient's needs. Above all, in radiation departments, it may be difficult for patients to obtain the desired information regarding modality and diagnosis because such information is subdivided when described on a website., Objective: The purpose of this study is to suggest a hospital website search behavior model by analyzing the browsing behavior model using a Bayesian network from the perspective of one-to-one marketing., Methods: First, we followed the website access log of Hokkaido University Hospital, which was collected from September 1, 2016, to August 31, 2017, and analyzed the access log using Google Analytics. Second, we specified the access records related to radiology from visitor browsing pages and keywords. Third, using these resources, we structured 3 Bayesian network models based on specific patient needs: radiotherapy, nuclear medicine examination, and radiological diagnosis. Analyzing each model, this study considered why some visitors could not reach their desired page and improvements to meet the needs of visitors seeking radiology-related information., Results: The radiotherapy model showed that 74% (67/90) of the target visitors could reach their requested page, but only 2% (2/90) could reach the Center page where inspection information, one of their requested pages, is posted. By analyzing the behavior of the visitors, we clarified that connecting with the radiotherapy and radiological diagnosis pages is useful for increasing the proportion of patients reaching their requested page., Conclusions: We proposed solutions for patient web-browsing accessibility based on a Bayesian network. Further analysis is necessary to verify the accuracy of the proposed model in comparison to other models. It is expected that information provided on hospital websites will be improved using this method., (©Ryusuke Suzuki, Teppei Suzuki, Shintaro Tsuji, Kensuke Fujiwara, Hiroko Yamashina, Akira Endoh, Katsuhiko Ogasawara. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 19.01.2021.)

Background: Pharmacists play an important role in promoting people's health in Japan, which has an aging population. Hence, it is necessary that the distribution of pharmacists meets the population's needs in each region. This study projects the future supply and demand for pharmacists in pharmacies to consider an optimal distribution of pharmacists., Methods: The future supply of pharmacists working in pharmacies in Hokkaido is projected using system dynamics modeling, according to their career path. The demand is projected based on the number of prescriptions, sourced from publicly available sources. The analysis period is 2015-2040. The estimated demand is converted into the number of pharmacists and the sufficiency is evaluated using sufficiency ratio (supply/demand ratio). Sensitivity analyses of the sufficiency ratio were conducted to estimate the effects of changes in parameters such as national exam pass rate, enrollments, attrition rates, the number of prescriptions per pharmacist, and diffusion of newly licensed pharmacists., Results: The projected supply, in 2025 and 2040, is 1.24 and 1.56 times, respectively, as that in 2015 and the demand is 1.11 and 0.98 times, respectively. In 2015, although the sufficiency ratio in Hokkaido overall is 1.19, the ratios are higher in urban medical areas and lower than 1 in rural medical areas, such as Minamihiyama, Emmon, and Nemuro. By 2040, the sufficiency ratios are greater than 1 for all areas except for Emmon and higher than 2 in some areas. The sensitivity analyses found that the sufficiency ratio was most sensitive to diffusion of newly licensed pharmacists and the number of prescriptions per pharmacist., Conclusion: Optimal distribution should be considered, as the results reveal a possible shortage in the number of pharmacists in rural medical areas in 2015-2025. Conversely, as the demand is projected to decrease after 2025 with a population decrease, future supply should be determined in order not to cause an oversupply after 2025. Refinements of the projection model should be conducted since the related factors such as the roles of pharmacists will change over time.

Objective : This study aims to determine the characteristics of Type 2 diabetic patients who are more likely to cause high-cost medical expenses using the Bayesian network model. Methods : The 2011-2015 receipt data of Iwamizawa city, Japan were collected from the National Health Insurance Database. From the record, we identified patients with Type 2 diabetes with the following items: age, gender, area, number of days provided medical services, number of diseases, number of medical examinations, annual healthcare expenditures, and the presence or absence of hospitalization. The Bayesian network model was applied to identify the characteristics of the patients, and four observed values were changed using a model for patients who paid at least 3607 USD a year for medical expenses. The changes in the conditional probability of the annual healthcare expenditures and changes in the percentage of patients with high-cost medical expenses were analyzed. Results : After changing the observed value, the percentage of patients with high-cost medical expense reimbursement increased when the following four conditions were applied: the patient "has ever been hospitalized", "had been provided medical services at least 18 days a year", "had at least 14 diseases listed on medical insurance receipts", and "has not had specific health checkups in five years". Conclusions : To prevent an excessive rise in healthcare expenditures in Type 2 diabetic patients, measures against complications and promoting encouragement for them to undergo specific health checkups are considered as effective.

Background:   Telemedicine as a technology is expected to resolve issues such as doctor shortages and disparities in medical services. However, high costs of system installation and maintenance inhibit its widespread use. Introduction:   This study involved a cost minimization analysis for installation of a teleradiology system in the Hokkaido prefecture of Japan. Conditions under which system utilization is cost-efficient and system utilization is effective for cost reduction were analyzed. Materials and Methods:   A cost minimization analysis was conducted using three geospatial points of 50, 100, and 200 km from Sapporo city, the prefectural capital of Hokkaido, assuming a central imaging diagnosis center in Sapporo. The analysis was conducted from the standpoint of both patients and requesting hospitals. Results:   From the patient's standpoint, a cost reduction effect was observed at all three distances from system installation. In contrast, from the hospital's standpoint, a cost reduction effect was found only when teleradiology examination was conducted from a distance of at least 100 km from Sapporo. Discussion:   Results show that the cost reduction effect for patients increased as the travel distance increased. Although the teleradiology service is beneficial for a wide range of patients, the financial burden on requesting hospitals is significant. Conclusions:   The following conditions were found necessary to reduce the requesting hospital's financial burden: the hospital should be far from the imaging diagnosis center, an inexpensive system is to be selected, and the system needs to be utilized continuously.

Background: In Cambodia, the age-standardized prevalence of diabetes mellitus has increased in both men and women. The main objective of this study was to identify factors associated with diabetes medication adherence among people with diabetes mellitus in poor urban areas of Phnom Penh, Cambodia., Methods: A cross-sectional study was conducted in 2017 using a structured questionnaire for face-to-face interviews by trained interviewers. The participants were people with diabetes mellitus who were the active members of a peer educator network, lived in poor urban areas of Phnom Penh, and attended weekly educational sessions during the survey period. Diabetes medication adherence was measured using four items of modified Morisky Medication Adherence Scale. Participants were classified into two groups based on their adherence score: 0 (high adherence) and from 1 to 4 (medium or low adherence). Sociodemographic characteristics; medical history; accessibility to health services; and knowledge, attitude, and practices related to diabetes mellitus were examined. A multiple logistic regression analysis was conducted adjusting for sex, age, marital status, and education levels., Results: Data from 773 people with diabetes were included in the analyses. Of the total, 49.3% had a high level of diabetes medication adherence. A high level of adherence was associated with higher family income (≥50 USD per month) (adjusted odds ratio [AOR] = 5.00, 95% confidence interval [CI] = 2.25-11.08), absence of diabetes mellitus-related complications (AOR = 1.66, 95% CI = 1.19-2.32), use of health services more than once per month (AOR = 2.87, 95% CI = 1.64-5.04), following special diet for diabetes mellitus (AOR = 1.81, 95% CI = 1.17-2.81), and absence of alcohol consumption (AOR = 13.67, 95% CI = 2.86-65.34)., Conclusions: High diabetes medication adherence was associated with better family economic conditions, absence of diabetes mellitus-related complications, and healthy behaviors. It would be crucial to improve affordable access to regular follow-ups including promotion of healthy behaviors through health education and control of diabetes mellitus-related complications., Competing Interests: Morisky WidgetTM, MMASTM, MMAS4 TM, MMAS-8 TM, Morisky Medication Adherence Protocol TM, and Morisky Medication Adherence Scale TM, is protected by U.S. and International Trademark and Copyright laws. Permission for use is required. MMAS Research LLC collects fees in exchange for licenses to use this scale in research. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Robot-assisted radical cystectomy is becoming a common treatment for bladder carcinoma. However, in comparison with open radical cystectomy, its cost-effectiveness has not been confirmed. Although few published reviews have compared total costs between the two surgical procedures, no study has compared segmental costs and explained their impact on total costs., Methods: A systematic review was conducted based on studies on the segmental costs of open, laparoscopic, and robot-assisted radical cystectomy using PubMed, Web of Science, and Cochrane Library databases to provide insight into cost-effective management methods for radical cystectomy. The segmental costs included operating, robot-related, complication, and length of stay costs. A sensitivity analysis was conducted to determine the impact of the annual number of cases on the per-case robot-related costs., Results: We identified two studies that compared open and laparoscopic surgeries and nine that compared open and robotic surgeries. Open radical cystectomy costs were higher than those of robotic surgeries in two retrospective single-institution studies, while robot-assisted radical cystectomy costs were higher in 1 retrospective single-institution study, 1 randomized controlled trial, and 4 large database studies. Operating costs were higher for robotic surgery, and accounted for 63.1-70.5% of the total robotic surgery cost. Sensitivity analysis revealed that robot-related costs were not a large proportion of total surgery costs in institutions with a large number of cases but accounted for a large proportion of total costs in centers with a small number of cases., Conclusions: The results show that robot-assisted radical cystectomy is more expensive than open radical cystectomy. The most effective methods to decrease costs associated with robotic surgery include a decrease in operating time and an increase in the number of cases. Further research is required on the cost-effectiveness of surgeries, including quality measures such as quality of life and quality-adjusted life years.

A common cause for image retakes in mammography is lack of proper positioning. Image retake is a potential hazard of increased radiation exposure to patient, patient discomfort and pain. Therefore, a mammographer has to provide fast exams with fewer retakes. Although evaluation of how a mammographer is effectively positioning has been studied in many ways, little research has been conducted to analyze visual attention. In this study, eye tracking system was adopted to detect eye movements and locations within a participants' visual fields during positioning. Eye tracking system has been widely used for assessing technical skills and risk awareness, and for comparing the skills between experts and novices. Two skilled mammographers and two novices were recruited. Positioning related activities were divided into two phases: patient's observation and breast positioning. Breast positioning was sub-divided into three stages to compare visual attention between experts and novices using heatmap and gaze plot. Although the expert tended to check each point, the novices tended to have a relatively short gaze of the outer breast region was observed. In the future, a comparative evaluation using clinical images is necessary; however, the eye tracking system to visualize attention contributes to medical safety during positioning.

Objective: To investigate comparative road user crash and fatality rates in Japan between 2000 and 2010 in the elderly and young., Methods: Data from the Japan Ministry of Health, Labor and Welfare Vital Statistics Database and the Institute for Traffic Accident Research and Data Analysis were used to calculate crash rates by age group, vehicle, and license category., Results: Fatal crash rates per 100,000 licensed drivers for 4-wheeled motor vehicle drivers decreased by 53, 56, and 42 percent among the 65-69, 70-74, and ≥75 age groups between 2000 and 2010, respectively, compared to 66 and 60 percent among the 16-19 and 20-24 age groups, respectively. Fatal crash rates per 100,000 licensed riders for 2-wheeled motor vehicles decreased by 64, 23, and 33 percent in the 65-69, 70-74, and ≥75 age groups, respectively. Similarly, fatal crash rates per million population among bicyclists and pedestrians decreased in all age groups but were highest in the elderly age group in all years; the annual fatal crash rate for elderly pedestrians was 3 to 10 times higher than that for younger pedestrians., Conclusions: Despite the overall decrease in the elderly crash and fatal crash rates in all road use categories, elderly pedestrians are more susceptible to road traffic crashes and are more likely to be killed than younger persons. Further research may reduce this risk.

In the present study, we investigated the possible tick vectors that can transmit Theileria orientalis in eastern Hokkaido, Japan. Questing ticks collected from three different districts, Taiki, Otofuke, and Shin-Hidaka, of Hokkaido included Ixodes persulcatus, Haemaphysalis megaspinosa, Haemaphysalis douglasi, and Ixodes ovatus, while all the ticks collected from Yonaguni island of Okinawa were identified as Haemaphysalis longicornis. When the ticks were screened by polymerase chain reaction (PCR) for T. orientalis, the parasite was commonly detected among all tick species. Genotype-specific PCR assays revealed that all tick species in Hokkaido were predominantly detected with type 2, while ticks collected from Okinawa (H. longicornis) were predominantly detected with type 1. Consistent with the genetic diversity of T. orientalis in ticks, genotyping PCR assays from cattle grazed in the same Hokkaido sampling locations identified type 2 as the most prevalent genotype. This study provides the first identification of I. persulcatus, H. megaspinosa, H. douglasi, and I. ovatus as possible tick vectors of T. orientalis, and finds that the variety of vectors apparently capable of transmitting T. orientalis is wider in Japan than expected. The authors suggest that tick control strategies should be modified in Hokkaido based on the seasonal activities of ticks identified in the present study., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Background: Human immunodeficiency virus (HIV) prevalence is relatively lower in Sri Lanka than in other Asian countries; however, the number of HIV-infected persons has rapidly increased in recent years., Methodology: A baseline study on HIV, acquired immunodeficiency virus (AIDS), and sexually transmitted infections (STI) knowledge, attitude, and practice was conducted at two construction sites in Sri Lanka from January to February 2007 to design an effective intervention strategy for the construction workers., Results: Among 611 respondents (mostly males, mean age 32.8 years), nearly two-thirds lived away from home. Knowledge was fairly good on AIDS prevention but poorer on STI than on HIV. Some misconceptions were also observed. A high percentage did not consider HIV/AIDS as their own personal issue, and over 50% respondents expressed discriminatory attitudes towards HIV positives. Condom access was limited due to social and cultural norms. Mobility was not significantly associated with practice of prevention of HIV and STI., Conclusion: This study showed that the construction workers were not specially at higher risk of HIV at that time. In order to minimize the potential risk of infection, however, it would be effective to reduce stigma and discrimination among them through the prevention program, working together with community or religious leaders in the areas. More comprehensive assessment among other population groups would also be beneficial to identify their risk of infection.

Theileria orientalis is one of the benign species of Theileria that is widely distributed in Japan and is sometimes responsible for serious economic losses in the livestock industry. In the present study, we surveyed the current status of T. orientalis infection in grazing cattle in the eastern areas of Hokkaido (Taiki, Otofuke, Shintoku, and Shin-Hidaka districts) using molecular methods, as well as traditional methods, of diagnosis. The genes encoding the major piroplasm surface protein (MPSP) and p23 of T. orientalis were identified using highly detectable polymerase chain reaction (PCR). Results of the MPSP-PCR assay indicated that grazing cattle in these districts, after about 1.5 months pasturage, showed high rates of infection, ranging from 10.0-64.8%. Although the main MPSP and p23 genotypes detected were the Ikeda- or Chitose-types, an MPSP gene closely relating to that found in Okinawa prefecture, and a p23 gene closely relating to the Australian (Warwick) Buffeli-type gene, were found in the cattle in Shintoku and Shin-Hidaka districts. The present survey indicated that there were at least five types of T. orientalis classified by their MPSP genes in Hokkaido, Japan, and that T. orientalis infection rates are still high in this region.

Background: Rabies remains endemic in Sri Lanka despite a strong government patronized anti-rabies campaign. Personal, cultural or religious beliefs have been thought to influence health practices that could render rabies prevalent in the country., Methodology: The knowledge, attitudes, and beliefs of 580 household heads/members from Nuwara Eliya District, Sri Lanka, regarding rabies were explored through a structured questionnaire. An improvement/deterioration in their knowledge and practices after the use of information and education campaign (IEC) materials was assessed through a repeat exploration at an interval of four weeks., Results: Respondents showed inclination toward animal birth control (60%) rather than elimination methods (24%). There was disparity between pet owners enthusiasm to take pets for rabies inoculation (57%) and their ability to show dog vaccination cards (40%). Almost twice more pet owners than non-pet owners believed that it is their responsibility to control the population of roaming pet dogs (aOR=1.78; 95% CI: 1.14 to 2.76). The rabies leaflets were very effective in informing the people on how to deal with rabid animals, the earliest schedule for anti-rabies vaccine (ARV), and repeat vaccination., Conclusions: Awareness and proper attitude toward rabies management and canine population control are adequate among the rural Sinhalese and Buddhist populations of Sri Lanka; however, their current health practices should be improved. The rabies KAP could be further enhanced through the use of IEC materials.

Objective: Large-scale clinical trials have demonstrated that beta blocker therapy improves the prognosis of dilated cardiomyopathy (DCM), but cardiac events sometimes occur even in patients showing favourable response to the therapy. In this study, the usefulness of meta-iodobenzyguanidine (MIBG) in predicting cardiac events was investigated in DCM patients successfully receiving long-term treatment with beta blockers., Methods: The subjects were 53 patients with DCM (including 10 women; mean age, 56.5+/-10.9 years) who could continue beta blocker therapy for more than 6 months. MIBG was performed within 1 year of commencing the therapy. The extent score, severity score and washout rate were obtained from single photon emission computed tomography images. At the same time, left ventricular ejection fraction (LVEF) and left ventricular end diastolic diameters were measured by echocardiography. The endpoints were cardiac events (cardiac death and admission to hospital due to heart failure or arrhythmia), and patients were observed for an average of 1314+/-986 days (150-4100 days)., Results: Cardiac events occurred in nine patients during the observation period. The multivariate statistical analysis demonstrated that the delayed extent score was the strongest significant predictive factor, (hazard ratio 1.036, P<0.01). while LVEF was not a predictive factor. Both the improvement of LVEF and MIBG were significant predictive factors. The improvement of washout rate was the strongest., Conclusion: Parameters of MIBG but not of LVEF were useful in predicting cardiac events in DCM patients whose condition had been successfully stabilized by the introduction of beta blockers.

Objective: It is not rare for patients with cardiomyopathy to be asymptomatic for long periods or to show improved cardiac function following various medical interventions. Conversely, cardiac events sometimes occur in those patients, requiring close observation. We assessed the usefulness of 123I-metaiodobenzylguanidine myocardial scintigraphy (MIBG) to predict the occurrence of cardiac events in patients with stable cardiomyopathy., Methods: The subjects comprised 74 outpatients with stable cardiomyopathy. MIBG was performed calculate the extent score, severity score, washout rate (WR), and heart-to-mediastinum ratio. At about the same time, the left ventricular ejection fraction (LVEF) by echocardiography and the plasma brain natriuretic peptide were measured. The mean observation period extended for 741+/-437 days with an end point of cardiac events (cardiac death, heart failure requiring hospitalization, and arrhythmias requiring hospitalization)., Results: During the mean follow-up period, 15 cardiac events occurred. Results of multivariate analysis revealed that LVEF was the most powerful predictor of cardiac events (0.006, p < 0.01). However, WR was the only significant predictor of hard events such as cardiac death (1.171, p < 0.001) and cardiac events in the group of patients who preserved cardiac function with LVEF 0.4 or higher (1.079, p < 0.05)., Conclusion: Combined use of LVEF and WR is useful to predict the occurrence of cardiac events in patients with stable cardiomyopathy.

Purpose: The usefulness of 123I-metaiodobenzylguanidine (MIBG) myocardial scintigraphy in predicting the effectiveness of beta-blocker therapy in dilated cardiomyopathy (DCM) was investigated from the standpoint of long-term prognosis., Methods: The subjects were 53 DCM patients in whom beta-blockers had been successfully introduced and used for 6 months or longer. When symptoms were stable before the introduction of beta-blockers and for up to 1 year thereafter, MIBG myocardial single-photon emission computed tomography was performed and the images analysed to obtain the extent score (EXT), severity score (SEV) and washout rate (WR). At the same time, echocardiography was performed to measure left ventricular ejection fraction (LVEF). Thereafter, patients were placed under observation for an average of 1,314+/-986 days, with the occurrence of cardiac events as the endpoint., Results: The degree of improvement in WR after introduction of beta-blockers was a significant predictor of cardiac events. In fact, none of the patients whose improvement in WR was valued at 10 or higher had cardiac events. Accordingly, using improvement in WR of 10 as the cut-off value, the patients were divided into two groups, "improved" and "unimproved". There were significant differences between the groups in respect of early EXT, early SEV and WR before the introduction of beta-blockers. As regards predictors of WR improvement, multivariate logistic regression analysis demonstrated that early EXT, WR and LVEF were significant predictors., Conclusion: This study shows that, from the standpoint of long-term prognosis, DCM patients who would benefit the most from beta-blocker therapy are those with low early EXT and early SEV and high WR before beta-blocker introduction regardless of LVEF values.

Loop-mediated isothermal amplification (LAMP) is a novel DNA amplification method that amplifies a target sequence specifically under isothermal conditions. The product of LAMP is detected by the turbidity of the reaction mixture without electrophoresis. The objective of this study was to develop a rapid sexing method for bovine preimplantation embryos using LAMP. The first experiment was conducted to optimize the DNA extraction method for LAMP-based embryo sexing. The DNA of single blastomeres was extracted using three methods: heat, NaOH, and proteinase K-Tween 20 (PK-TW) treatments. Sexing was performed with two LAMP reactions, male-specific and male-female common reaction, after DNA extraction. The rates of correct determination of sex were 88.9-94.4%, with no difference among methods. The sensitivity and accuracy of LAMP-based embryo sexing were evaluated in the next experiment. The proportion of samples in which the sex was correctly determined was 75-100% for one to five biopsied cells. Lastly, in vivo-derived embryos were examined to verify the usefulness of LAMP-based embryo sexing, and some of these fresh, sexed embryos were transferred into recipient animals. The time needed for sexing was <1 h. The pregnancy rate was 57.4% and all calves born were of the predicted sex (12 male and 21 female). Therefore, LAMP-based embryo sexing accurately determined gender and is suitable for field application.

We extract and analyze the decision factors of introducing image information system by ISM (Interpretive Structural Modeling) method to determine the criteria and structure for system selection. As a result, 15 factors were extracted, and the structure and relation among factors became clear.

To investigate the clinical applicability of the three-dimensional (3D) myocardial imaging using a newly developed system (the Application Visualization System-Medical Viewer), thallium-201 myocardial single photon emission computed tomography was performed in 19 patients with previous myocardial infarction before and after treatment with nisoldipine. We have developed a new method for automatically reconstructing 3D imaging for the stereoscopic evaluation of myocardial perfusion. The left ventricular myocardial volume with a radioisotope count > or = 50% of maximum was calculated by using the conventional surface rendering method. With these images, the effect of nisoldipine on myocardial perfusion was assessed and the myocardial volume with a radioisotope count > or = 50% of maximum was compared. In fifteen (88%) of 19 patients, myocardial perfusion increased in the infarct areas after nisoldipine treatment. Nisoldipine significantly increased the myocardial volume with a radioisotope count > or = 50% of maximum from 141 +/- 17 to 153 +/- 18 ml on the stress 3D imagings. These findings indicate that nisoldipine improved myocardial perfusion during exercise. 3D imaging provided stereoscopic assessment of the changes in myocardial perfusion following treatment with nisoldipine and also detected transient enlargement of the left ventricular lumen induced by exercise.

Factors affecting viability of IVF-derived bovine blastocysts after freezing and thawing were investigated. A total of 1,101 ova matured and fertilized in vitro were cultured under 2 different conditions, 1) in TCM-199 on granulosa cell monolayers at 5% CO(2) in air and 2) in synthetic oviduct fluid (SOF) medium without somatic cell support at 5% CO(2), 5% O(2), 90% N(2). All blastocysts that developed from the 2 different culture systems were individually classified into 4 grades of embryo quality and were then frozen by conventional slow freezing. Developmental rates of the IVF-derived ova to blastocysts and the survival rates of the frozen-thawed blastocysts were not different between the SOF medium (16 and 49%) and the co-culture system (13 and 61%, respectively). Survival of frozen-thawed blastocysts was affected by embryo quality in both the SOF and co-culture systems (P<0.001). Blastocysts produced in vitro were also individually classified into 3 developmental stages and were then cultured for 3 d in the co-culture system with granulosa cells after freezing and thawing. There was a difference in the survival rate of frozen-thawed embryos between blastocyst developmental stages (early vs mid, P<0.05; mid vs expanded, P<0.01; early vs expanded, P<0.001). The post-thawing survival rate of blastocysts frozen at Day 7 (62%) of culture was higher compared with that of Day 8 (45%), but there was no difference in survival rate between Day 7 and 8 of culture. The results indicate that the quality and developmental stage of blastocysts are important factors influencing their survival after freezing and thawing.

MIBG-myocardial SPECT was performed on patients with dilated cardiomyopathy (DCM) undergoing treatment with beta blocker (Nipradilol). The findings of MIBG-myocardial SPECT were compared with the changes in cardiac function obtained by echocardiograms. The patients enrolled in the study were seven males who has been diagnosed as definitely suffering from DCM according to diagnostic guidelines provided by the Ministry of Health and Welfare. The patients were aged 57.5 +/- 10.2 years. Following intravenous administration of 111 MBq (3 mCi) of MIBG, myocardial SPECT was taken 20 minutes, and 4 hours later. The washout rate of the left ventricular wall was higher in the unchanged group (40.7 +/- 1.2%) than in the improved group (30.3 +/- 6.1%). Both the early and delayed images showed higher extent and severity scores for the unchanged group than for the improved group. A correlation of LVEF with the washout rates was demonstrated (r = -0.819, p < 0.05). A correlation was also observed between the variations in LVEF before and after beta blocker therapy with the washout rates (r = -0.969, p < 0.01), MIBG-myocardial SPECT suggested possibility of the evaluation of severity and prognosis in the patients with DCM.

The present study was conducted to investigate the effect of human leukemia inhibitory factor (hLIF) addition to synthetic oviduct fluid medium (SOFM) supplemented with human serum (HS) on the development of in vitro matured and parthenogenetically activated bovine oocytes. The oocytes matured for 30 h were exposured to ethanol (7%, 7 min) and cytochalasin B (5 mug/ml, 5 to 6 h). The treated oocytes were cultured for 5 d in SOFM supplemented with HS, and Day-5 morulae were cultured for 2 d in SOFM supplemented with HS and with or without hLIF (5000 U/ml) to investigate the subsequent in vitro development to the blastocyst stage. Of the 1531 oocytes that were parthenogenetically activated, 592 (37.5%) cleaved to the 2- to 8-cell stage and 174 (13.8%) developed to the morula stage. The addition of hLIF at the morula stage resulted in a significantly (P<0.01) higher rate of development to the blastocyst stage in the medium with hLIF (55.9%) than without hLIF (28.9%). The mean cell number per blastocyst developed in the medium with hLIF was also significantly (P<0.01) higher than that developed in the medium without hLIF. To evaluate the viability, 6 parthenogenetically developed blastocysts were transferred to 3 recipient heifers (2 embryos per heifer), while in 2 other recipient heifers estrus was prolonged after transfer. The plasma progesterone levels of the 2 recipient heifers at the 28th day after transfer were 8.1 ng/ml and 9.0 ng/ml, but pregnancy was not observed by ultrasonic scanning. The present results indicate that the addition of hLIF to in vitro-produced, Day-5 parthenogenetic bovine morulae significantly improves the subsequent development to the blastocysts stage; however, the present method still does not promote for development of parthenogenetic fetuses in cattle.

111In-labeled low-density lipoprotein (LDL) was administered to Watanabe heritable hyperlipidemic rabbits (WHHL group) and control rabbits (control group) to evaluate its biodistribution and scintigraphic images by gamma-camera and radioactivity of each organ. With external imaging, the heart, liver, kidney, bone and spleen of each rabbit were observed. By setting the region of interest, the liver/heart ratio of the WHHL group was significantly lower than that of the control group (p < 0.05), the plasma half life of LDL was longer and radioactivity in blood, heart and aorta was higher in the WHHL group. Each aorta was autoradiographed and significant accumulation of 111In-labeled-LDL was recognized in the aortic arch, bifurcation of intercostal and celiac artery in the WHHL group. By the use of labeled LDL with the combination of gamma-camera, it is capable of detecting the regulation of lipoprotein metabolism and imaging atherosclerotic lesions externally.

A retrospective study on complications especially related to operative or postoperative management was carried out in 1000 pacemaker implantations in 717 patients between September, 1972 and December, 1986. In 33 of our series (4.8%), 24 pacing failure occurred within two weeks of implantation. Flange-type leads had the highest incidence of complications. Wedging the electrode close to the longitudinal axis of the heart was found to be the best placing, assuming that the tip of the electrode and the section immediately adjacent were pointing downward. There were 6 cases of diaphragmatic pacing which could not be corrected through programming. No relation with the position of the electrode could be found. We recommend using bipolar pacing to lower the incidence of diaphragmatic pacing. We also had 9 patients with lead fractures (1.3%); these included 3 cases with silicone insulation breaks and 6 cases with wire fractures which occurred closely proximal to the area where the lead was fixed to the vessels. No relationship between the ratio of lead fractures and their brand was found. Five patients developed infections, all of them late postoperatively, over a period of 8 months to 5 years postop. Of these, there were 3 cases with postoperative prolonged hematoma at the pocket site, and 4 cases which had required lead repositioning because of pacing failure. The incidence of infection in our series was low when compared to previous reports, probably due to local use of one gram of Kanamycin during the operation and active chemotherapy performed short term postoperatively. To manage infection of the skin pocket, the pacemaker was removed and a new pacemaker was implanted in the opposite side. There was 7 early postoperative deaths. One of them due to cardiac tamponade caused by perforation of the cardiac wall by temporary electrode lead. The resustation was unsuccessful.

We treated a 37 year old woman with venous aneurysm along left side of the neck. In the beginning, she was asymptomatic and with increase in size of the venous aneurysm she experienced severe pain. Pathohistological examinations revealed a destructive change of the venous wall and thrombosis. Therefore, in cases of venous aneurysm along the neck, such aneurysm should probably be treated surgically to prevent the occurrence of pulmonary embolism.

The effect of three new fluoroquinolones on theophylline kinetics and the urinary excretion of metabolites was studied in 5 healthy subjects (3 male, 2 female). All subjects received serial, single i.v. infusions of theophylline (aminophylline, 250 mg) over 60 min after 200 mg doses of a quinolone (enoxacin, ofloxacin, norfloxacin) every 8 h for 3 consecutive days, the quinolone being administered up to the day following theophylline administration. Pretreatment with ofloxacin and norfloxacin did not influence theophylline disposition, but theophylline clearance fell from 0.054 to 0.027 l.h-1.kg-1 in the presence of enoxacin, without a change in the apparent volume of distribution. Enoxacin, too, was the sole compound to increase the urinary excretion of theophylline (33.2 vs 43.9 mg, before vs after treatment), and significantly to decrease the excretion of 3-methylxanthine (3-MX), 1-methyluric acid (1-MU) and 1,3-dimethyluric acid (1,3-DMU) in 24-h urine samples (from 19.8 to 7.16 mg, from 28.3 to 10.3 mg and from 68.8 to 49.5 mg, respectively). The effect of the quinolones on hepatic drug metabolizing enzyme activity was investigated in each subject using the ratios of 6-hydroxycortisol to total 17-hydroxycorticosteroids and to free cortisol in 24-h urines as an index of the hepatic P-450-dependent enzyme system. No significant difference in ratio was observed between control and other treatments. It is concluded that the theophylline-enoxacin interaction was largely due to inhibition of a metabolic system other than the common hepatic P-450 system.

The in vitro and in vivo inactivation of tobramycin by carbenicillin, ticarcillin, or piperacillin was investigated by the enzyme immunoassay method in clinically employed dosages. After the addition of an 80-mg dose of tobramycin to 4- to 5-g doses of a penicillin in 100 ml of 0.9% saline or distilled water, the degradation profile of tobramycin appeared to follow a biexponential pattern of decay. Remarkable losses (30 to 40%) of tobramycin combined with carbenicillin or ticarcillin were observed within 1 h, as compared with the later decline. The combination of tobramycin with piperacillin was least inactivating. When the admixture of tobramycin with carbenicillin or piperacillin used in the in vitro study was infused to six volunteers over 1 h, the observed maximum concentrations of tobramycin were on the average 66 and 74% for carbenicillin and piperacillin, respectively, of that observed after tobramycin alone was given. In contrast, the value obtained for tobramycin in combination with piperacillin was close to 90% of the control value. The elimination half-lives of tobramycin combined with the penicillins were slightly shorter than those of tobramycin alone, indicating that the interaction occurs even in patients with normal renal function.

A comparative pharmacokinetic study between a sustained-release theophylline tablet (Theona) and aminophylline powder following multiple oral administrations every 12 h at a 200 mg theophylline dose was performed in ten healthy adult volunteers. As the results, theophylline in Theona revealed almost completely absorbed as is aminophylline. A peak-trough difference with Theona was less than half of that with aminophylline powder. These results suggest that Theona has excellent characteristics as a sustained-release preparation. In addition, in order to investigate dose-dependent kinetics for theophylline, the relationship between average plasma level and dosage was examined with Theona. The plasma level showed proportional change at the low concentrations. When the plasma level was close to 10 micrograms/ml, however, dosage increment results in an increasingly greater change of plasma level, which may indicate a high risk of toxicity.

A 55 year-old male with traumatic rupture of the pericardium, diaphragm and spleen, and with crush of the pancreas was successfully operated upon. The diagnosis of rupture of the diaphragm was done on the chest X ray on admission, and the rupture of the pericardium was diagnosed at the time of laparotomy and thoracotomy. The ruptured spleen and the crushed pancreas tail were removed, and the ruptured pericardium and diaphragm were closed successively.

During the past five years, 150 pacemaker implantations have been done at Hiroshima Prefectural Hospital for the treatment of atrioventricular block, sick sinus syndrome, or slow heartbeat with atrial fibrillation. The patients were divided into two groups by age: the older group of 18 patients over 80 years of age and the younger group of 132 patients under 79 years of age. A comparative study of these two groups was undertaken with respect to pre- and postoperative courses, underlying diseases, cardiac output at variable pacing rate, capture threshold, and prognosis. The older group has as satisfactory a course as the younger group. Seventeen patients out of 18 (94%) in the older group are leading normal productive lives at this writing, and 119 out of 132 (89%) in the younger group are also doing well. In the light of this five-year comparative study, it can be concluded that it is safe and rewarding to implant prosthetic cardiac pacemakers in symptomatic patients over 80 years of age.

Latamoxef (LMOX, Siomarin) at a dose of 2 g was intravenously administered to each of 23 patients undergoing the open heart surgery and the concentrations in serum, pericardial fluid and auricle of heart were measured. Pharmacokinetic observations are summarized below. The peak serum concentration (t = 0) was 227.3 micrograms/ml and the serum half-life (T1/2 beta) was 1.74 hours. In pericardial fluid, LMOX reached the peak concentration of 28.44 micrograms/ml at 4.9 hours and the half-life was 9.99 hours. In auricle of heart, LMOX reached the peak concentration of 42.78 micrograms/g at 6.9 minutes and the half-life was 1.74 hours. It was shown that LMOX penetrates well into the pericardial fluid and the auricle of heart, and it is considered that their levels exceed the minimal inhibitory concentration against a majority of clinical isolates except Pseudomonas aeruginosa.

The cardiovascular effects of isometric handgrip exercise were determined with a nonivasive method in the patient with artificial pacemaker. The arterial blood pressure was measured with mercury manometer as well as cardiac output by the dye dilution method with Indocyanin green before and after handgrip exercise. Isometric handgrip exercise produced a significant increase in the left ventricular ejection time, the left ventricular ejection time/the preejection period, the ejection time index/the isometric contraction time, the arterial blood pressure and cardiac output and a significant decrease in the preejection time and the isometric contraction time. Cardiac output was increased more remarkably in the negative Master two step test group than in the positive Master two step test group. There was found a significant positive relationship between the increase in cardiac output and P wave rate upon handgrip exercise.

Pretreatment for 3 days with oral ofloxacin or norfloxacin had no significant effect on the disposition of a single i.v. dose the theophylline in healthy volunteers.

The pharmacokinetics of fosfomycin, administered intravenously and orally at two different doses (20 and 40 mg/kg of body weight), was studied in seven volunteers. The elimination profile of this antibiotic, when administered intravenously, followed a two-compartment kinetic model, independent of dosage, giving an elimination half-life of 2.23 +/- 0.62 h and an average total volume of distribution at steady state of 0.34 liter/kg. Peak serum levels after rapid intravenous administration of 20 and 40 mg/kg were 132.1 +/- 31.8 and 259.3 +/- 32.5 micrograms/ml, respectively. Peak serum levels after oral administration were 7.1 +/- 1.6 and 9.4 +/- 3.6 micrograms/ml for the 20 and 40 mg/kg doses, respectively. During the first 24 h after administration, an average of 80% of the intravenous doses and less than 25% of the oral doses were recovered in the urine.

Cefmenoxime (CMX) at a dose of 1 g was administered intravenously to each of 10 patients undergoing thoracotomy, and concentrations of CMX in the serum and pleural fluid were measured. Serum concentration of CMX reached its peak of 43.71 micrograms/ml at 1 hour and decreased to 4.15 micrograms/ml at 3 hours after the administration. The concentration of CMX in the pleural fluid reached its peak of 7.61 micrograms/ml at 3 hours and decreased slowly 5.26 micrograms/ml at 7 hours after the administration. A clinical study with 21 patients was performed to evaluate the effect of CMX as a prophylactic antimicrobial agent in thoracotomy. Patients received intravenous administration of 4 g/day of CMX for 7-10 days following operations. Each patient was evaluated daily for fever, sign of allergic reaction, and wound infection and other symptoms. No apparent infection occurred in those clinical patients except 1 patient with a suspected infection, and 1 case of allergic reaction as exanthema was observed during this study. Prophylactic effect of CMX against postoperative infection after thoracotomy was good.

The pharmacokinetics of intravenously administered cefotiam (CTM), using a two-compartment or three-compartment open model, have been investigated in patients undergoing thoracic surgery. Patients (Group 1) given 1 hour drip infusion of 1 g of CTM, had the peak serum level (32.8 micrograms/ml) at 1 hour, and the peak pleural effusion level (8.3 micrograms/ml) was achieved at 2.08 hours. Patients (Group 2) given an one-shot intravenous injection of 1 g of CTM, had the maximum pleural effusion concentration (8.35 micrograms/ml) at 2.67 hours. Patients (Group 3) given 1 hour drip infusion of 1 g of CTM, had the mean concentration (2.3--2.5 micrograms/g) in the pleural tissue for 2 to 3.5 hours. Clinical study comprising 20 patients was performed to evaluate the effects of CTM as a prophylactic antimicrobial agent in the thoracic surgery. Patients received intravenous administration of 4 g/day of CTM for 7--10 days. Each patients was evaluated daily for fever, signs of allergic reaction, and wound infection and so on. No infections occurred in these thoracic surgery except 1, and no serious side effects was observed in this study.

Twenty nine patients with sick sinus syndrome were treated from November, 1972 through July, 1976. Six cases had sinus bradycardia, 14 cases had sinoatrial block/sinus arrest and 9 cases had bradycardia-tachycardia syndrome. Twenty five patients received the implantation pacemaker with good result. There was found that an adequate pacing of the heart was effective for the control of the attack of tachyarrhythmia in the case with bradycardia-tachycardia syndrome.

Following two-compartment kinetic analysis, the effect of loading of transfusion with sodium bicarbonate on methotrexate disposition was investigated in 13 cases with malignant tumor, being treated with high-dose methotrexate. The mean values of total body clearance, when administered at doses 50 mg and 100 mg per kg body weight, were 0.369 and 0.402 (l/h) per kg, respectively. No significant relationship was observed between alpha value and total amount of transfusion, of urine or dosage of sodium bicarbonate. The other kinetic parameters on elimination, beta value, K10 and total body clearance, did not also correlate with those values described above. These results suggest that the elimination profile of methotrexate show linear kinetics, and that massive administration of transfusion with sodium bicarbonate be not necessary if pH value of urine exceeds 7.0.