Tomoaki Imamura

Yusho disease was first reported in October 1968 in western Japan. Although a previous survey revealed that Yusho patients have suffered from various symptoms for 40 years after the outbreak of Yusho, some symptoms could be caused by aging. Therefore, we compared the prevalence of symptoms and medical histories (symptoms or patient-reported diseases) between Yusho patients and healthy controls to demonstrate the effects of Yusho on health conditions. We conducted a survey of healthy controls who had already registered to a survey company and created a dataset of symptoms and medical histories. We then merged the healthy control data with the Yusho survey data obtained from The Ministry of Health, Labour, and Welfare of Japan. Statistical analyses were performed using a chi-square analysis for the incidence of symptoms. Symptoms included in the major diagnostic criteria for Yusho, such as pigmentation and acneform eruption, were expectedly higher in the Yusho patients than in the healthy individuals. Symptoms that could be caused by aging, such as general fatigue, arthralgia, and numbness in the extremities, were also significantly higher in the Yusho patients after adjustment for age, indicating the possibility that Yusho may cause various systemic symptoms and diseases.

Half-lives of blood levels of 2,3,4,7,8-Pentachlorodibenzofuran (PeCDF) are varied in Yusho patients. The objective was to evaluate a relationship between half-lives of PeCDF levels and types of SNP rs10249788 of aryl hydrocarbon receptor (AHR) gene in 93 Yusho patients. Based on physical symptoms, age, sex, body mass index and other factors, we set up suitable calculation formulas to fit the actual PeCDF levels thorough rates of change in PeCDF. We found that patients with C/T SNP had longer half lives than patients with C/C and T/T SNPs. Patients with T/T SNP are known to express higher amount of AHR mRNAs. However, detailed analysis could not be carried out in T/T group due to a limited number of patients (n = 11). Further research is warranted to determine the cause of the longer half-lives in C/T patients.

With increasing global interest in intentional food contamination, expert meetings have been held by the G8, while the U.S. government has proposed policies for preventing food terrorism and intentional contamination. However, Japan has no food defense policy, and some food companies are concerned about an impending terrorism and contamination crisis. We developed a Food Defense Checklist for Food Producers and Processors and published the details on the website. We also developed tentative Food Defense Guidelines for Food Producers and Processors on the basis of the checklist. In this study, we tested the usability of the guidelines through a hearing survey regarding food plants. We also compared the checklist with the implementation manual for the approval system of Comprehensive Sanitation Management and Production Process (the Japanese equivalent of the HACCP). We organized the comments gleaned from the hearing survey and provided a detailed explanation of the guidelines. As the HACCP has been adopted by Japanese food companies, we included both precautionary measures and the HACCP perspective in the explanation regarding the rapid dissemination of information. The guidelines are useful for Japanese food companies, and it is important to disseminate knowledge on this topic and implement food defense measures.

The relationships among dioxin isomers are not well understood. This study aimed to clarify the relationships among isomers using two methods. First, the relationships between isomers and symptoms were analyzed by analysis of variance. Second, concentrations and half-lives were determined for each isomer in each patient, and correlation coefficients for the concentrations and half-lives among isomers were calculated. Two isomers very similar to 2, 3, 4, 7, 8-pentachlorodibenzofuran (2, 3, 4, 7, 8-PeCDF) were correlated with symptoms of Yusho disease. The correlation coefficients among three isomers similar to 2, 3, 4, 7, 8-PeCDF were very high at 0.98, indicating that there may be a mechanism which maintains constant ratios among these isomers.

Blood levels of dioxins in Yusho patients have been measured for 10 years. The purposes of this study were to determine the half-lives of dioxins on the basis of the data obtained from Yusho patients and to compare the half-lives of the compounds. Linear regression analysis was performed using the binary logarithmic value of each dioxin level as the dependent variable and the year of measurement as the independent variable. The linear coefficient obtained from this linear regression analysis was the reciprocal number of the half-life. The relationship between the blood dioxin levels estimated in 2004 and the reciprocal number of half-life was evaluated. Of the studied dioxins, the concentrations of some compounds were strongly correlated with that of 2,3,4,7,8-PeCDF. For 2 such compounds, the correlation coefficient of the reciprocal numbers of half-life were greater than the correlation coefficient of the logarithmic values of the estimated concentrations. Of these 2 compounds, the concentration of 3,3,4,4,5,5-HxCB was at least 50 times less than that of the 2,3,4,7, 8-PeCDF in rice oil: however, their current concentrations are equivalent. Patients with high levels of 2,3,4,7,8-PeCDF also showed high levels of 3,3,4,4,5,5-HxCB. Yusho patients may have a disease-specific mechanism to supply 3,3,4,4,5,5-HxCB.

Introduction: There are inconsistent data about the effectiveness of prehospital physician-staffed advanced cardiac life support (ACLS) on the outcomes of out-of-hospital cardiac arrest (OHCA). Furthermore, the relative importance of bystander-initiated cardiopulmonary resuscitation (BCPR) and ACLS and the effectiveness of their combination have not been clearly demonstrated. Methods: Using a prospective, nationwide, population-based registry of all OHCA patients in Japan, we enrolled 95,072 patients whose arrests were witnessed by bystanders and 23,127 patients witnessed by emergency medical service providers between 2005 and 2007. We divided the bystander-witnessed arrest patients into Group A (ACLS by emergency life-saving technicians without BCPR), Group B (ACLS by emergency life-saving technicians with BCPR), Group C (ACLS by physicians without BCPR) and Group D (ACLS by physicians with BCPR). The outcome data included 1-month survival and neurological outcomes determined by the cerebral performance category. Results: Among the 95,072 bystander-witnessed arrest patients, 7,722 (8.1%) were alive at 1 month, including 2,754 (2.9%) with good performance and 3,171 (3.3%) with vegetative status or worse. BCPR occurred in 42% of bystander-witnessed arrests. In comparison with Group A, the rates of good-performance survival were significantly higher in Group B (odds ratio (OR), 2.23; 95% confidence interval, 2.05 to 2.42; P < 0.01) and Group D (OR, 2.80; 95% confidence interval, 2.28 to 3.43; P < 0.01), while no significant difference was seen for Group C (OR, 1.18; 95% confidence interval, 0.86 to 1.61; P = 0.32). The occurrence of vegetative status or worse at 1 month was highest in Group C (OR, 1.92; 95% confidence interval, 1.55 to 2.37; P < 0.01). Conclusions: In this registry-based study, BCPR significantly improved the survival of OHCA with good cerebral outcome. The groups with BCPR and ACLS by physicians had the best outcomes. However, receiving ACLS by physicians without preceding BCPR significantly increased the number of patients with neurologically unfavorable outcomes.

Recently, methods for measurement of dioxins in the blood have improved. Also, techniques for analyzing large quantities of data have been developed, such as data mining. Even in subjects with elusive characteristics, it is becoming possible to find previously unknown characteristics by checking all combinations of symptoms.

Since 1968, when the Yusho poisoning incident occurred, annual physical, dermatological, dental, and ophthalmological and laboratory examinations, collectively called Yusho health checks, have been conducted for Yusho patients. The Yusho incident was a health hazard caused by intake of rice-bran oil contaminated with PCB and PeCDF; therefore, since 2001 the levels of dioxins such as PeCDF in the blood have been measured in applicants. Here, we investigated correlations among findings from various medical examinations and those between those findings and PeCDF, PCB, and PCQ. Subjects were Yusho patients who underwent Yusho annual health checks and had their levels of PeCDF measured between 2001 and 2004. The results of 4 years of health checks of those who underwent the health checks for 2 years or longer were aggregated to extract representative inspection items by principal component analysis. We also investigated the presence or absence of correlations among these items and PeCDF, PCB, and PCQ levels in blood. Using 49 variables extracted by principal component analysis as objective variables, we determined that there were correlations between the following combinations: arthralgia, A/G ratio and PeCDF level, ophthalmological symptoms such as excessive eye discharge and PCB level, and total cholesterol, inferior gingival pigmentation and PCQ level.

The half-life of 2,3,4,7,8-penta-chlorodibenzofuran (PeCDF) in the Yusho patients has been reported to be approximately seven years. In the present study, we estimated the half-life of PeCDF using data from the medical check-ups of more than 300 Yusho patients. We performed linear regression analysis with a binary logarithm of PeCDF blood level in Yusho patients as the dependent variable, and the measurement year as the independent variable. Our results showed that there were many patients who had shown no reduction of their blood PeCDF level for several years. This result contradicts the previously reported half-life period. Therefore, we believe that a more complicated excretion model needs to be established to explain the discrepancy we found. We hypothesized that there might be two mechanisms of PeCDF assimilation in human digestive tract. In the present study, we also used our hypothesis to simulate PeCDF excretion in Yusho patients.