Analysis of hepatitis B surface antigen mutations in Mongolia: molecular epidemiology and implications for mass vaccination.

Although the potential significance of hepatitis B surface antigen (HBsAg) mutants for failure of immunization has been studied in some endemic countries, whether the "a" determinant variants are responsible for vaccine failure in Mongolia remains unknown. Fifty-nine HBsAg-positive children (age: 8.8 +/- 0.9 years) who had been observed during the nationwide survey of vaccinated cohorts conducted in 2004 were subjected to molecular analyses of hepatitis B virus (HBV). Partial S gene sequences encoding amino acids (aa) 40-171 of HBsAg were determined in 57 children (96.6%) who had detectable HBV DNA. Phylogenetic analysis of the S gene sequences revealed that genotype D accounted for 93.0% and genotype A for 5.3%. Only one child (1.7%) had HBVs of genotypes A and D. HBsAg mutations were found in 17 (29.8%) children ranging from 1 to 4 aa per subject (mean +/- SD, 1.6 +/- 0.9 aa). Pro127Thr and Thr118Ala were the most common substitutions, which occurred in 6 (10.5%) and 3 (5.3%) subjects, respectively; none had Gly145Arg. There were no significant associations in the prevalence of HBsAg mutations with age, sex, residential area, or vaccination status against hepatitis B. Analysis of the deduced amino acid sequence of the entire preS1/preS2/S gene revealed that eight genotype D isolates and one genotype A isolate were quite similar to previously-reported wild-type isolates, suggesting that they are essentially wild-type, but not vaccine-induced mutants. In conclusion, the results demonstrate that hepatitis B surface gene mutants do not play a significant role in vaccination failure in Mongolia.

Correlation coefficients between the dioxin levels in mother's milk and the distances to the nearest waste incinerator which was the largest source of dioxins from each mother's place of residence in Tokyo, Japan.

BACKGROUND: To observe the relationship between the PCDD/F and Co-PCB levels in samples of human breast milk and nearby waste incinerators in Tokyo, Japan. METHODS: Breast milk was taken from 240 mothers residing in Tokyo, Japan to measure and analyze the concentrations of polychlorinated dibenzo-p-dioxins (PCDDs; 14 congeners), polychlorinated dibenzofurans (PCDFs; 15 congeners), and coplanar polychlorinated biphenyls (Co-PCBs; 12 congeners) contained in the fat. Individual milk samples (about 50 ml) were obtained from the mothers 30 days after delivery, between the months of June and September in 1999 and 2000. A map of Tokyo was used to measure the distances between each mother's place of residence and the closest public and industrial waste incinerators. RESULTS: The distances to the nearest waste incinerators bore no apparent correlations with the congeners of PCDD/Fs and Co-PCBs. The distances were also uncorrelated with the mean toxic equivalent quantities (TEQs) of PCDD/Fs (the sum of PCDDs and PCDFs), Co-PCBs, and the total PCDD/Fs and Co-PCBs. CONCLUSIONS: Although waste incinerators were the largest source of dioxins in Japan at the time of the study, the dioxins levels of mother's milk bore no apparent relationships with the distances between the mothers' domiciles and the nearest waste incinerators. In this study, several meaningful factors were not taken into account, namely, the wind direction, the level of dioxin emitted from each incinerator, the level of environmental pollution of dioxins, and the average time the mothers stayed at home each day. A full understanding of these points awaits future studies.

Different effects of blood pressure on mortality from stroke subtypes depending on BMI levels: a 19-year cohort study in the Japanese general population--NIPPON DATA80.

To evaluate the relationship between blood pressure and cerebrovascular death depending on body mass index (BMI) levels, we analysed a database of 9338 subjects from the National Integrated Project for Prospective Observation of Non-communicable Disease and its Trends in the Aged, which was originally conducted a baseline survey in 1980 and followed up in 1999. Relative risk (RR) and a 95% confidence interval (CI) of death from total stroke, cerebral infarction, and intracerebral haemorrhage after adjusting for age, sex, serum cholesterol, albumin, glucose, the use of antihypertensive agents, a past history of diabetes, BMI, smoking, and drinking were estimated with the Cox-proportional hazard model in the BMI tertile groups of a representative Japanese population. Cutoff points of BMI tertiles are 21.2 and 23.8 kg/m2. The results indicated that a 10 mmHg systolic blood pressure (SBP) increase was associated with mortality from intracerebral haemorrhage at low and middle BMI groups (RR= 1.38 and 1.23; 95% CI=1.17-1.62 and 1.03-1.47, respectively). SBP was positively associated with mortality from cerebral infarction in middle and high BMI groups (RR=1.19 and 1.21; 95% CI=1.06-1.33 and 1.06-1.38, respectively). The effects of diastolic blood pressure on intracerebral haemorrhage and infarction had the same tendency as those of SBP. These results suggested that the causal effect of blood pressure on stroke subtypes might be modified by BMI.

PCDDs, PCdfs and Co-PCBs in human breast milk samples collected in Tokyo, Japan.

AIM: To observe the distribution of PCDD/Fs and Co-PCBs in samples of human breast milk collected in Japan. METHODS: Using high-resolution gas chromatography, milk samples for polychlorinated dibenzo-p-dioxins (PCDDs; 14 congeners), polychlorinated dibenzofurans (PCDFs; 15 congeners) and coplanar polychlorinated biphenyls (Co-PCBs; 12 congeners) from 240 mothers residing in Tokyo were analysed. There were 120 donors each of primiparae and secundiparae, each group including 60 donors aged 25 to 29 y ("the younger group") and 60 aged 30 to 34 y ("the older group"). Individual milk samples (about 50 ml) were obtained 30 d after delivery in 1999 and in 2000. RESULTS: The mean toxic equivalent (TEQ) level of PCDD/Fs (the sum of PCDDs and PCDFs) was 14.9 pg TEQ/g fat, of Co-PCBs 10.6 pg TEQ/g fat, and the total sum of PCDD/Fs and Co-PCBs was 25.6 pg TEQ/g fat. The mean TEQ levels of PCDD/Fs, Co-PCBs, and total PCDD/Fs and Co-PCBs were higher in primiparae than in secundiparae. In each of these, the levels were higher in the subgroup of older mothers. In the secundiparae, the mean levels were lower in the group of mothers who had breastfed their first babies than in those who bottle-fed or partly bottle-fed their first born. CONCLUSIONS: The concentrations of PCDD/Fs and Co-PCBs in the breast milk of Japanese women were slightly lower than those described in previous studies conducted in Japan and other countries; and the concentrations of PCDD/Fs and Co-PCBs in the breast milk were influenced mainly by the mother's age and nursing history.

Factors relating to the cardiac sequelae of Kawasaki disease one month after initial onset.

UNLABELLED: This study aimed to determine the risk factors related to the presence of cardiac sequelae 1 mo after initial onset and to examine the preventive effect of the early administration of high-dose gamma-globulin (GG) on cardiac sequelae in patients with Kawasaki disease. Patients treated with high-dose GG of 2000 +/- 100 mg kg(-1) were selected as subjects from the 15th nation-wide survey in Japan. Univariate and logistic multiple variable analyses were used to test the effects of background variables such as age and gender, variables relating to laboratory findings such as the percentage of neutrophil leucocytes, and variables relating to the GG treatment on the presence of cardiac sequelae. The odds ratios were significantly higher for males (1.48), those younger than 1 y of age (1.71), recurrent cases (2.42), and those with a low haematocrit (<32.5%) (1.45) and high percentage of neutrophil leucocytes (>68%) (1.63). The odds ratio was low for those who started GG administration in less than 6 d from onset between the patients with and without cardiac sequelae. The odds ratio for the duration of GG treatment was not significantly different between those with and without cardiac sequelae. CONCLUSION: Patients who received early administration of GG, less than 6 d from onset of the disease, had a lower risk than those received GG more than 6 d from the onset. The percentage of neutrophil leucocytes and the haematocrit level are useful indicators in predicting the development of cardiac sequelae.

Incidence survey of Kawasaki disease in 1997 and 1998 in Japan.

OBJECTIVE: To describe the results of a nationwide epidemiologic survey of Kawasaki disease for the 2-year period 1997 and 1998. DESIGN: We sent a questionnaire to all hospitals with 100 beds or more throughout Japan (2663 hospitals) requesting data on patients with Kawasaki disease. Study items included name, sex, date of birth, date of initial hospital visit, diagnosis, address, recurrence, sibling cases, gammaglobulin treatment, and cardiac lesion in the acute stage or 1 month after onset. RESULTS: Of the 2663 hospitals, 68.5% responded, reporting 12 966 patients-7489 males and 5477 females. Of the total patients reported, 6373 (incidence rate of 108.0 per 100 000 children <5 years old) occurred in 1997, and 6593 (111.7) in 1998. More than one half of the patients (54.9%) were <2 years old and 81.6% were <4 years old. In males, the incidence rates of cardiac lesions were 27.2 in the acute stage and 10.1 a month after onset. In females, the rates were 16.7 and 5.2, respectively. The incidence rates of cardiac lesions were highest in the youngest age group (<6 months old) both in the acute stage and 1 month after onset. The rates decreased with increasing ages. Although frequency of giant aneurysms was not high at the acute stage, it did not decrease 1 month after onset. CONCLUSION: The incidence rates have been steadily increasing for 11 years since 1987. The rate in 1998 was over 1.5 times higher than that in 1987. The age and sex distributions were identical in each survey. Although most of the cardiac lesions at the acute stage decreased to half or less 1 month after onset, giant aneurysms did not decrease and existed persistently after 1 month.

Repeatability of the questionnaire for the aging level indices.

The purpose of the study is to confirm repeatability of the series of self-administrating questions, which can be applied in large community populations. In 1994 and 1995, two surveys were conducted for the residents at Minamikawachi, Japan with a same questionnaire. The number of respondents for the both surveys was 887. Kappa statistics of all items of the series of questions for aging level indices were significantly high. Kappa statistics were over 0.4, and repeatability is good or excellent in 28 items of all the 45 items. The statistics of the items for medical treatments of chronic diseases were high, in such as diabetes (0.846) and hypertension (0.604). For activity of daily livings, such as shopping (0.619), kappa statistics were also high, but that of eating (0.162) was low. The statistics of subjective symptoms were moderate, however, that of impairment of hearing (0.672) was high, and that of decline of interest in opposite sex (0.256) were low. On the other hand, kappa statistics of acute diseases were low, in such as bone fracture (0.073). Correlation coefficients of the comprehensive aging level indices are around 0.6 among the people of 65 years old or older. In conclusion, the repeatability of the questions and indices were good, and they are appropriate to apply to communities.

[Case-control study of risk factors for cedar pollinosis among parents of 3-year-old children].

PURPOSE: To identify risk factors associated with cedar pollinosis among parents of three-year-old children. METHODS: The subjects were parents whose children underwent health examination at the age of three years in September and October 1997 in Tochigi prefecture. We distributed questionnaires to the examinees beforehand with the request that they be filled in and brought to the examination site. Information on parents' environmental factors (place of residence, type and structure of housing, and distance from roads with heavy traffic), and mothers' past history and family history of allergic diseases was obtained. We defined cedar pollinosis in terms of three symptoms, sneezing, nasal discharge, and nasal obstruction, between February and May. Controls were those who did not have any of the three symptoms. Environmental factors were assessed with univariate and multivariate analyses using unconditional logistic models. Maternal genetic factors were also analyzed with odds ratios and 95% confidence intervals calculated for each. We also compared odds ratios of environmental factors between groups with and without genetic factors. RESULTS: Of the parents of children taking the health examination, 90.2% took part (2,968 of 3,291 couples). Information was obtained from 2,846 mothers and 2,905 fathers. Mother and father cases were 312 and 229, and controls were 1,857 and 1,934, respectively. For the univariate analysis of environmental factors, place of residence (residential area/agricultural area), type of housing (apartment complex/solitary house), structure (reinforced concrete building/wooden house), and distance from heavy traffic (< 100 m/100 m+) were positively related to cedar pollinosis. For the multivariate analysis using unconditional logistic models, the odds ratio was significantly high for distance from heavy traffic (< 100 m/100 m+) among fathers. Mothers' past history and family history of allergic diseases showed high odds ratios for cedar pollinosis. We classified groups with and without past and family histories of allergic diseases (group with and without genetic factors) for assessment with multivariate analyses. Odds ratios for the group with an allergic history were higher than for those without such a history, but difference for factors such as, distance from heavy traffic type of housing, and structure were not statistically significant. CONCLUSION: Risk of cedar pollinosis increases with distance from heavy traffic among fathers. Mothers with histories of allergy show slightly elevated odds ratios for environmental factors, but without statistic significance.

Relationship between breast milk feeding and atopic dermatitis in children.

OBJECTIVE: To determine whether or not the breast milk feeding has a role in the prevalence of atopic dermatitis among children. METHODS: The target population of the study was all children participating in health check-up program for 3-year-old children in 60 municipalities locating 10 selected prefectures during designated 2 months between October and December 1997. Using a questionnaire, information on nutrition in infants (breast milk only, bottled milk only, or mixed), parity, mothers' age at birth, and a history of atopic dermatitis was obtained. Besides, data on potential confounding factors were obtained. RESULTS: Questionnaires from 3856 children (81.6% of those who were to participate in the programs, and 96.4% of children who participated them) were analyzed. After the adjustment for all potential confounding factors using unconditional logistic models, the risk of atopic dermatitis was slightly higher among children with breast milk (odds ratio [OR] = 1.16 with 95% confidence interval [CI] 0.96-1.40). Mothers' age at birth (OR for those who were more than 30 years or older in comparison with those who were younger than 30 years = 1.15; 95% CI, 0.96-1.37) and those with second or later parity orders (OR = 1.14, 95% CI; 0.95-1.35) showed odds ratios that were higher than unity without statistical significance. CONCLUSION: Breast milk elevates the risk of atopic dermatitis slightly without statistical significance; the risk may be, however, higher in children in second or later parity orders.

A case-control study of Creutzfeldt-Jakob disease in Japan: transplantation of cadaveric dura mater was a risk factor.

A case-control study was conducted to reveal the relative risk of cadaveric dura mater graft transplantation for Creutzfeldt-Jakob disease. Fifty-two cases with Creutzfeldt-Jakob disease that were reported to the surveillance of the disease, and 102 age- and sex-matched hospital controls were selected. Information on family history, occupations, and medical history was collected. Eight cases and no control had a history of cadaveric dura mater graft transplantation. Surgical operations without the dura mater graft, blood transfusion, and acupuncture did not elevate the risk.

A multicenter collaborative study on the risk factors of cardiac sequelae due to Kawasaki disease: a one-year follow-up study.

OBJECTIVE: To measure the prevalence of cardiac sequelae 1 y after the onset of Kawasaki disease and determine the risk factors associated with these cardiac sequelae. MATERIAL AND METHODS: 1594 patients who initially visited one of the 87 target hospitals in 1996 for Kawasaki disease participated. Selection of the target hospitals was based on a nationwide survey. The patients were followed-up and information concerning cardiac sequelae occurring within 1 y of onset was obtained by mail survey. RESULTS: The prevalence of cardiac sequelae 1 mo after onset was 10.2% and decreased to 4.2% in 1 y. The prevalence was higher among males than females and higher in patients less than 1 y and 5 ys or older than in 1-4 year-olds. Of the patients with cardiac sequelae at 1 mo, the sequelae disappeared in 60.7% after 1 y. Analysis revealed low serum albumin as a risk factor related to the occurrence of cardiac sequelae 1 y after onset. Of the 1594 patients, 10 had giant anuerysms and 3 had a fatal outcome. CONCLUSIONS: Approximately 60% of cardiac sequelae due to Kawasaki disease that developed within 1 mo after onset disappeared in 1 y. The odds ratio was significantly higher among patients with a low serum albumin level 1 y after onset.

[Chronological trend of the incidence rate of Creutzfeldt-Jakob disease in Japan].

OBJECTIVE: The purpose of this study was to find whether the number of incidents of Creutzfeldt-Jakob disease has increased during the last decade in Japan. METHODS: The chronological trend was observed by examining the data from a nationwide epidemiologic survey conducted by a special committee sponsored by the Ministry of Health and Welfare of Japan in May 1996. The subjects of the survey were patients with Creutzfeldt-Jakob disease who had been diagnosed between January 1985 and May 1996. Although the number of patients reported each year increased continually during the 11-year 5-month period, there were two issues that remained to cast doubt on the accuracy of this apparently obvious chronological trend: (1) the existence of hospitals that did not respond to the survey, and (2) the existence of hospitals where no information was available before a specific time during the observation period. To make up for the incomplete data, the following two methods were proposed: (1) for those hospitals where the precise annual incidence was not known, the average annual incidence for those years when the information was available should be used to make up for the missing data and (2) when a hospital did not have the information for certain years, it would be considered to be a nonrespondent for those years; the response rate should be calculated year-by-year; then the total number of patients should be obtained by the reported number of patients divided by the response rate. The first method underestimates the annual trend if a trend does exist. To evaluate the trend mathematically, linear regression and quadratic regression models were used, in which the independent variable was the calendar year, the dependent variable, the number of patients. RESULTS: With either method, a trend for increases in incidence was noted. Statistical significance was obtained for the increasing trend in each model. It was found that the quadratic regression model was a better fit than the linear model. CONCLUSION: The incidence of Creutzfeldt-Jakob disease in Japan has increased during the last decade.

[Building aging level indices based on ability to perform personal care and household management activities].

Defining aging as deterioration of the ability required for the activities of daily living with increasing age, we developed a formula for estimating the age of aging. In 1994 and 1995, a questionnaire survey was conducted for 11,592 individuals (4,885 men, mean age 61.6, standard deviation 14.6; and 6,677 women, mean age 63.2, standard deviation 14.8) who were members of 7 cohorts (5 community-based cohorts and 2 cohorts of examiners at a health-promotion center). The questionnaire included three groups of questions related to medical treatment, aging-related symptoms, and personal care (ADL; Activities of Daily Living) and household management (IADL: Instrumental ADL). Multiple regression analysis was made by sex and age group (over 65 years old, under 65 years old) using age as a dependent variable and the three question categories as explanatory variables. Using multiple regression analysis by question category, five items were abstracted from each of the three groups, so that a total of 15 items were abstracted from all questions. Five items were then abstracted from the 15 by multiple regression analysis, and the predicted aging age for an individual is estimated using this statistical model from the results of the questionnaire survey. The predicted aging age is significantly associated with age (r = 0.40-0.49, p = 0.0001). The difference between the predicted aging age and age is greater among the older or younger people. The expected predicted aging age is estimated using regression analysis of the predicted aging age on age. Aging level indices by sex and age groups were determined by the difference between the expected predicted aging age and age. We are planning to carry out an epidemiological study on the risk factor for aging using the aging level indices in seven cohorts.

Factors related to cardiac sequelae of Kawasaki disease.

Among the 35.210 patients with Kawasaki disease who were reported in nationwide surveys from 1991 to 1996, 83% were treated with gamma-globulin (GG). Those treated with a total dose of 1000 mg/kg (9098 patients) and 2000 mg/kg (7012 patients) were selected as the subjects of the study on the relationship between the development of cardiac sequelae, in particular of giant aneurysms, and related factors using logistic regression models. Among the two groups that received 1000 mg/kg and 2000 mg/kg, respectively, the odds ratios for cardiac sequelae were significantly high for males, those < 6 months and > or = 7 years of age, and typical or recurrent cases. Except for those < 6 months of age, the odds ratios of all the factors mentioned above were higher for the incidence of giant coronary aneurysms than those for cardiac sequelae. The preventive effects of GG therapy for cardiac sequelae and in particular giant aneurysms, were significantly low when GG administration was initiated on day 8 or later after onset. In the group treated with 1000 mg/kg, the preventive effect was low when GG administration was spread over 3 days or longer. To prevent the development of cardiac sequelae, in particular giant coronary aneurysms, gamma-globulin therapy should be started as soon as possible and be completed within 2 days.

[Relationship between breast milk and atopic dermatitis in children].

OBJECTIVE: To determine whether or not dioxins and furans in breast milk have a role in the prevalence of atopic dermatitis among children. METHODS: The target population of the study was all children participating in health check-up program for 3-year-old children in Tochigi Prefecture in September and October 1997. Using a questionnaire, information on nutrition in infants (breast milk only, bottled milk only, or mixed), parity, mothers' age at birth, and a history of atopic dermatitis was obtained. Besides, data on potential confounding factors were obtained. RESULTS: Questionnaires from 2,968 children (85.3% of those who were to participate in the programs, and 90.2% of children who participated them) were analyzed. The risk of atopic dermatitis was higher among children with breast milk (odds ratio [OR] = 1.37 with 95% confidence interval [CI] 1.02-1.83) and those with mixed nutrition (OR = 1.21, 95% CI: 0.94-1.57) in comparison with children with only bottled milk. Mothers' age at birth (OR for those who were more than 30 years or older in comparison with those who were younger than 30 years = 1.27; 95% CI, 1.01-1.62) and those with second or later parity orders (OR = 1.32, 95% CI; 1.04-1.67) were also risk factors of the dermatitis after the adjustment for some potential confounding factors. CONCLUSION: Breast milk elevates the risk of atopic dermatitis slightly; the risk is, however, higher in children in second or later parity orders. If the PCDDs and PCDFs in breast milk cause the dermatitis, this would contradict the assumed metabolism of these chemicals in human bodies.

Effects of gamma-globulin on the cardiac sequelae of Kawasaki disease.

Our aim was to delineate the effect of various factors, such as sex, age, serum albumin levels, and the timing of gamma-globulin (GG) therapy, on cardiac sequelae of Kawasaki disease. The patients with Kawasaki disease who were reported at the 1995-1996 nationwide survey and received 2000 mg/kg at specified hospitals were selected as the subjects of the study. A total of 2221 patients actually received the basic dose. The relationships of the GG therapy with the cardiac sequelae, sex, age, timing of GG administration (the date of initiation and duration of the regimen following disease onset), and serum albumin levels were examined by using logistic regression analysis. The odds ratios for the cardiac sequelae in patients with Kawasaki disease were high in males (1.63), in those under the age of 1 year (1.54), and in those with a serum albumin level <3.2 g/dl (2.64). The odds ratio was low in those who received GG before day 8 of the illness (0.69) or in those for whom the administration period was for 2 days or less (0.67). To prevent cardiac sequelae of Kawasaki disease it is desirable that GG therapy be started as soon as possible and completed within 2 days.

Process and current status of the epidemiologic studies on cedar pollinosis in Japan.

This paper reviews the present situation and future aspects of epidemiologic studies on Japanese cedar pollinosis. Increase of allergic rhinitis patients is observed in both the Patient Survey and the Reports on the Surveys of Social Medical Care Insurance Services, however, these surveys are conducted when cedar pollens do not pollute the air. Many have reported on the prevalence of pollinosis in limited areas but only a few nationwide epidemiologic surveys have been conducted. Most of the studies were conducted at special medical facilities such as university hospitals. There is a high possibility that patients who visit the specific facilities do not exactly represent the actual number of patients and epidemiologic pictures of pollinosis in Japan. The rapid advances in laboratory test methods may change the diagnostic criteria and increase the number of reported patients. Therefore, the prevalence of Japanese cedar pollinosis in Japan has not been determined yet. Determination of the prevalence of cedar pollinosis and description of the epidemiologic pictures constitute the essential steps toward the control of this clinical entity. Thus it is necessary to conduct an epidemiologic survey on Japanese representative samples with a standardized survey form with clear and concise diagnostic criteria.

Changes in epidemic patterns of Kawasaki disease in Japan.

OBJECTIVE: Clustering of cases of Kawasaki disease throughout Japan was noted three times during the period before 1986. During the ensuing 10 years, however, no nationwide epidemic has been recognized. The purpose of this study is to test the hypothesis that local outbreaks have persisted after 1987. METHOD: The data on 56 980 patients reported from 1987 through 1996 were classified according to the area of residence. The time trend of the incidence rate was compared by year and by quarter of the year (January to March, April to June, July to September and October to December) in 10 geographical areas in Japan. RESULTS: No nationwide outbreaks have been noted since 1987 in Japan, but the existence of local outbreaks of various magnitudes was recognized as occurring in different periods in certain areas. The incidence rates were continuously high in Area 1 between 1987 and 1988 and in Area 4 between 1995 and 1996. In Area 9 local outbreaks were noted on three separate occasions (from 1987 to the first half of 1988, between 1990 and 1991 and from the second half of 1992 to 1993). No clusterings were witnessed in other areas during the 10-year period. CONCLUSION: The current annual number of patients ranges from 5000 to 6000, and local epidemics occur in various areas. The current epidemiologic patterns support the infection theory for the etiology of this disease.