A high incidence of intussusception in Japan as studied in a sentinel hospital over a 25-year period (1978-2002)

The development of second-generation rotavirus vaccines requires knowledge of baseline incidence rates for intussusception in infants prior to vaccine introduction. To obtain such estimates we reviewed clinical records in a hospital that served as the major provider of paediatric beds in a local community in the northern part of Japan. During the 25-year period (1978-2002), there were 91 hospitalizations due to radiologically confirmed intussusception in children <5 years of age, of which 45% were <1 year of age. Assuming that all children with intussusception in the area had been admitted to this hospital, there were an average of 185 and 78 hospitalizations per 100000 person-years for children <1 year old and 5 years old respectively. There was period-to-period variability with no long-term secular trend in the incidence of intussusception. The incidence rate in Japan was among the highest thus far reported, providing further evidence of geographic variability.


Relationship between the type of urinary incontinence and falls among frail elderly women in Japan.

Urinary incontinence and falls are serious problem among elderly people, because of restriction of the Activities of Daily Living (ADL) and Quality of Life. Previous studies have examined the association between urinary incontinence and falls. However, results have been inconsistent. In Japan, with the rapid aging of the society, the number of elderly women who have urinary incontinence and are at risk of falling is increasing. We investigated the relationship between type of urinary incontinence and risk of falls among elderly users of day-care services in a long-term care system. Our study population comprised 118 ambulatory women. At baseline, we evaluated incontinent status, lower extremity muscle strength, balance ability, ADL, and Instrumental ADL. We asked subjects about number of falls every 4 months during a year. In univariate analysis, lower extremity muscle strength (p = 0.001) and mixed incontinence (p = 0.050) differed significantly according to the fall status. Stress and urge incontinence were not significantly associated with falls. In logistic regression analysis, subjects who had mixed incontinence were 3.05 (95% confidence interval 1.01-10.2) times more likely to fall than those without. These results suggest that mixed incontinence have independent associations with falls. Incontinent status should be considered to prevent falls among elderly persons who are partially dependent and need support.

The Journal of Medical Investigation : JMI


Background exposure to PCDDs/PCDFs/PCBs and its potential health effects: a review of epidemiologic studies

Here we review epidemiologic studies dealing with the dietary intake and the body burden of polychlorinated dibenzo-p-dioxins (PCDDs)/polychlorinated dibenzo-furans (PCDFs)/ polychlorinated biphenyls (PCBs) in the general population, and potential adverse health effects of these substances, especially on the risk of diabetes mellitus and endometriosis, and on thyroid function and the neurodevelopment of infants. The mean or median intake of dioxin-related compounds among the general populations of various countries is lower than the maximum tolerable daily intake (TDI) set by the WHO in 1998 (4pg TEQ/kg/day). However, there have been few reports on the distribution of intake and the proportion of subjects whose exposure levels exceed the maximum TDL. At present, it remains unclear whether background exposure to dioxin-related compounds is associated with increased risk of diabetes (because of lack of longitudinal studies), endometriosis (because of lack of studies with sufficient statistical power), or altered thyroid function (because of inconsistent results on humans). Consistent results have been reported for the association between exposure to background levels of PCBs/dioxins, especially trans-placental PCBs, and defective neurodevelopment of infants in the U.S. and Europe. Thus, efforts should be made to further decrease the body burden among women of reproductive age by reducing the release of PCDDs/PCDFs/PCBs into the environment.


Multi-prefectural spread of gastroenteritis outbreaks attributable to a single genogroup II norovirus strain from a tourist restaurant in Nagasaki, Japan.

A series of gastroenteritis outbreaks caused by noroviruses (NVs) among tourist groups from several prefectures was associated with eating a lunch prepared by a restaurant in Nagasaki City, Japan, on 18 and 19 November 2003. A retrospective cohort study was performed to estimate the magnitude of the outbreak and identify the source of infection. Epidemiological information was obtained through the local public health centers in the areas where the illness occurred. Stool and vomit specimens and food and environmental samples were analyzed by reverse transcription-PCR with genogroup-specific primers. Positive samples were sequenced and analyzed phylogenetically. Of 1,492 tourists who ate a lunch prepared by the restaurant during the 2-day period, 660 (44.2%) developed illness, with an average incubation time of 31.2 h. Whereas NVs were not detected in any food samples, identical sequences most closely related to the Mexico genotype of genogroup II NV were found in specimens from case patients, restaurant staff, and the kitchen table. Food handlers were concluded to be the source of the outbreak as a result of the contamination of several meals. The series of outbreaks described here exemplifies the role of tourism as a contemporary way to distribute a single infectious agent to multiple and geographically remote areas.


Abnormal folic acid homocysteine metabolism as maternal risk factors for Down syndrome in Japan.

Japan has been considered as "a folate sufficient area", since traditional Japanese food contains an adequate amount of folic acid. However, the recent westernized food style of young Japanese mothers may affect the intake of folic acid among them. This food style may contribute to the occurrence of Down syndrome, which has proved to be linked to abnormal folate and homocysteine metabolisms. To preliminarily evaluate the levels of folic acid,homocysteine and other relevant factors which are associated with folate metabolism, among Japanese women who had pregnancies affected by Down syndrome. Blood samples from 31 women who had pregnancies affected by Down syndrome (DS) were obtained. 60 age-matched control blood samples were also obtained from mothers who had not experienced miscarriages or abnormal pregnancies (CONT). Plasma homocysteine and serum folic acid, vitamin B12, and B6 were measured and compared between DS and CONT. Furthermore, the frequency of MTHFR polymorphism (C677T) was also investigated. Plasma levels of homocysteine were significantly increased in DS mothers (p = 0.004). In contrast, serum levels of folic acid were significantly decreased in DS mothers (p = 0.0001). There were no significant differences in the vitamin B12 and B6 levels between DS and CONT. Also, the frequency of 5,10-methylenetetrahydrofolate reductase gene (MTHFR) homozygous polymorphism showed no differences between DS and CONT. Different levels of serum folic acid and plasma homocysteine between both groups may contribute to the occurrence of Down syndrome even in Japan. Although there was no significant difference in the frequency of MTHFR polymorphism between the groups, probably because of an inadequate number of samples, further studies may contribute to the understanding of the occurrence of Down syndrome in Japan.


An outbreak of gastroenteritis during school trip caused by serotype G2 group A rotavirus.

Between May14 and 18, 2001, there was an outbreak of acute gastroenteritis involving 45 school children out of a total of 107 (aged 11-12 years) attending a 3-day school trip. The epidemic curve characterized by a rapid onset and decline with a single peak incidence over a 5-day period resembled the pattern typical of a food-borne gastroenteritis outbreak. Epidemiological and virological investigations concluded, however, that this outbreak was caused by a single strain of serotype G2 group A rotavirus spreading to schoolmates from the primary case-pupil who had already been ill at the start of the trip. Efficient person-to-person transmission was likely to have occurred due to prolonged and close contacts under the conditions typical of such school trips. This study emphasizes the importance of including group A rotavirus infection as a possible cause of gastroenteritis outbreaks even in older children and adults.


Estimation of annual incidence, age-specific incidence rate, and cumulative risk of rotavirus gastroenteritis among children in Japan

Rotavirus gastroenteritis is a common childhood infection, but the exact morbidity of the disease is not well described in Japan. We aimed at estimating morbidity measures to determine the magnitude of rotavirus gastroenteritis. An estimate for acute infectious gastroenteritis of all causes, to which rotavirus gastroenteritis belongs, has been available since the enactment in 1999 of the Law concerning the Prevention of Infectious Diseases and Medical Care of Patients with Infectious Diseases. Using this estimate and another estimate for the detection proportion of rotavirus among outpatients with acute infectious gastroenteritis, we calculated the annual incidence, the age-specific annual incidence rate, and the cumulative risk by the age of 6 years for rotavirus gastroenteritis. The latter estimate was obtained by a meta-analysis of four independent studies previously performed in Japan. According to our estimates, approximately 800,000 children in Japan under the age of 6 years visit pediatric practices or the outpatient department of hospitals because of rotavirus gastroenteritis at a rate of 11 cases/100 persons/year, and one in two children will visit pediatricians before they go to primary school. Such pediatrician visits most frequently occur at the age of 1 year (27 cases/100 persons/year). Thus, the magnitude of the burden of rotavirus disease among Japanese children is substantial.


Randomized controlled trial of swaddling versus massage in the management of excessive crying in infants with cerebral injuries.

Infants with neonatal cerebral insults are susceptible to excessive crying as a result of difficulties with self-regulation. To compare the effectiveness of swaddling versus massage therapy in the management of excessive crying of infants with cerebral insults. Randomised three-week parallel comparison of the efficacy of two intervention methods. Infants with symptoms of troublesome crying and their parents were randomly assigned to a swaddling intervention group (n = 13) or a massage intervention group (n = 12). The amount of total daily crying decreased significantly in the swaddling group, but did not decrease significantly in the massage group. Infant behavioural profiles and maternal anxiety levels improved significantly in the swaddling group post-intervention. Parents in the swaddling group were more satisfied with the effectiveness of the intervention in reducing crying than parents in the massage group. Results indicate that swaddling may be more effective than massage intervention in reducing crying in infants with cerebral injuries.


The des-gamma-carboxy prothrombin index is a new prognostic indicator for hepatocellular carcinoma.

Des-gamma-carboxy prothrombin (DCP) has been reported to be an important prognostic factor in patients with hepatocellular carcinoma (HCC). Recently, a monoclonal antibody, 19B7, which recognizes the Gla domain of DCP, has been identified. The 19B7 antibody recognizes an epitope different from that recognized by MU-3, which is another antibody against DCP. In this study, the authors investigated the measurement of DCP using the antibodies MU-3 and 19B7, respectively, as a prognostic factor for patients with HCC who had solitary, small tumors and or Child Stage A HCC. One hundred four patients with HCC who had solitary, small tumors or Child Stage A tumors were enrolled in the study between 1991 and 2001. All patients were treated and were followed for a mean of 3.2 years. The authors analyzed the correlation between the DCP Index (DCP measured by MU-3 and DCP measured by 19B7) and patient prognosis. The patients were classified into 3 groups based on their DCP Index: 1) DCP negative (DCP < 40 milli arbitrary unit (mAU)/mL)); 2) low DCP Index (DCP > or = 40 mAU/mL; MU-3:19B7 ratio, < 3.0; and 3) high DCP Index (DCP > or = 40 mAU/mL; MU-3:19B7 ratio, > or = 3.0). The survival rate for patients in the high DCP Index group was lower compared with the survival rate for patients in the DCP-negative group and was significantly lower compared with the survival rate for patients in the low DCP Index group. In a univariate Cox proportional hazards model, the positive factors were high DCP Index and low DCP Index. Among the positive predictive factors that were analyzed using a multivariate Cox proportional hazards model were age (hazard ratio, 3.27; P = 0.006), low DCP Index (hazard ratio, 2.87; P = 0.012), and high DCP Index (hazard ratio, 12.3; P < 0.0001). The prognosis of patients who had a high DCP Index score was poorer compared with patients who had a low DCP Index score and patients who were classified as DCP negative. The authors concluded that the DCP Index is a prognostic indicator for patients with HCC.


Human T-lymphotropic virus type-I infection, survival and cancer risk in southwestern Japan: A prospective cohort study.

This study prospectively evaluated the associations of human T-lymphotropic virus type-I (HTLV-I) infection with survival and cancer incidence. The study base comprised 4297 adults (aged 40-69 years in 1993) who had either visited the outpatient clinic or who had received annual health check-ups at the A Hospital, Nagasaki, Japan, between 1985 and 1992 (HTLV-I seropositivity = 24.7%). During the follow-up period (1993-1999 or 2000), 290 deaths and 261 cases of malignant neoplasms occurred, including ten deaths and six incident cases of adult T-cell leukemia/lymphoma (ATL). After adjustment for gender, age and other covariates, HTLV-I seropositivity was associated with an increased mortality from all-causes excluding ATL (rate ratio, RR = 1.3, 95% confidence interval, CI = 1.0-1.7), all non-neoplastic diseases (RR = 1.5, 95% CI = 1.0-2.3) and heart diseases. HTLV-I infection was not found to be associated with an increased risk of developing total cancers other than ATL (RR = 0.98, 95% CI = 0.74-1.3), colorectal cancers, liver cancer or lung cancer, but was associated with a reduced risk of gastric cancer (RR = 0.42, 95% CI = 0.17-0.99). HTLV-I infection is associated with increased mortality from all-causes excluding ATL and all non-neoplastic diseases. HTLV-I carriers may not be at increased general cancer risk, but at reduced risk of gastric cancer.


Neonatal behavioral characteristics and later behavioral problems.

The purposes of this study were (1) to evaluate the usefulness of the Neonatal Behavioral Assessment Scale (NBAS) as a tool to assess the risk of later behavioral problems, (2) to analyze the relationship between neonatal behavioral characteristics and behavioral problems in childhood. Subjects were 77 very-low-birth-weight infants admitted to the NICU at the Nagasaki University Hospital, Nagasaki, Japan. The results suggest that behavioral characteristics such as poor motor performance, poor state regulation, and poor interaction ability in the neonatal period are risk factors for behavioral problems in childhood. The NBAS could help clinicians to identify neonates at risk of later behavioral problems.


Interleukin-10 promoter polymorphisms and liver fibrosis progression in patients with chronic hepatitis C in Japan.


Neonatal Behavioral Assessment Scale as a predictor of the later developmental disabilities of low birth-weight and/or premature infants.

The purpose of this study was to evaluate the usefulness of the Neonatal Behavioral Assessment Scale (NBAS) as a tool to assess the risk of later developmental disabilities. The study subjects were 209 low birth-weight and/or premature infants admitted to the NICU at the Nagasaki University Hospital, Nagasaki, Japan. These infants were examined using the NBAS at 36-38 (NBAS36), 40-42 (NBAS40) and 44-46 weeks (NBAS44) of postmenstrual age, and their developmental outcome was measured using standardized assessments at 5 years of age. Based on the results of diagnosis at 5 years of age, subjects were classified into three groups: Normal, Mild Disability and Severe Disability groups. Multinomial logistic regression analysis showed that lower Motor cluster scores for all assessment periods and lower Orientation cluster scores in the NBAS40 and NBAS44 were significantly associated with an increased risk of both Mild and Severe Disability. Also, the Range of State cluster scores for the NBAS44 were significantly related to the risk of Mild Disability, and the Reflexes cluster scores in the NBAS40 and NBAS44 were the best predictor of Severe Disability. In outcome prediction using the estimated regression coefficients, 94-97% of the subjects in the Normal group, 50-78% in the Mild Disability group and 71-85% in the Severe Disability group were correctly classified. The NBAS could help clinicians to develop a management protocol for infants at risk for developmental disabilities as well as to identify neonates at risk of developmental disabilities.


Preoperative serum level of CA19-9 predicts recurrence after curative surgery in node-negative colorectal cancer patients.

We hypothesize that a subset of node-negative colorectal cancer patients exists that is at high risk for recurrence after curative surgery. Preoperative serum levels of sialyl Lewisa (CA19-9), sialyl Lewisx (SLX), sialyl Tn (STN), and carcinoembryonic (CEA) antigens were analyzed for their value in predicting for such a group. One-hundred-forty-five patients with node-negative, T1-4, M0 colorectal cancers were divided into groups of low or high serum antigen levels. Disease-free interval served as the endpoint in evaluating the prognostic strength of each variable. Twenty-seven patients (18.6%) were included in the high group for CA19-9 antigen, 11 (7.6%) for SLX, 13 (9.0%) for STN, and 51 (35.2%) for CEA. The median follow-up was 62.1 months. As compared to those with low levels, patients with elevated CA19-9 had a shorter disease-free interval (P = 0.0026). No significant difference in disease-free interval was noted between low and high groups of SLX, STN, and CEA antigens. Cox regression analysis identified elevated serum CA19-9 level as a predictor for decreased disease-free interval, independent of T-stage or tumor location. Elevated preoperative serum levels of CA19-9 may serve as a useful marker in identifying patients with node-negative colorectal cancers at high risk for recurrence after surgery.


Lower-extremety muscle forces measured by a hand-held dynamometer and the risk of falls among day-care users in Japan.

To assess the relationship between the lower extremity muscle forces and risk of falls among the elderly who were using day-care services in the long-term care insurance system. The study population comprised 96 women aged 69 - 91 years. At baseline, we assessed ADL, functional capacity, isometric muscle forces of knee extension and ankle dorsiflexion obtained with a hand-held dynamometer. After 1 year, we asked subjects about falls during the follow up period. In univariate analysis, only the knee extensor strength (p = 0.003) and ankle dorsiflexor strength (p = 0.02) differed significantly according to the fall status. After adjustment for age using multinomial logistic regression analysis, the weak quadriceps group was 7.50 times more likely than the strong group to fall once (p = 0.02), and 5.00 times more likely to fall twice or more (p = 0.02). The weakest ankle dorsiflexor group was 5.09 times more likely than the strongest group to fall twice or more (p = 0.05). Our results indicated that the forces of knee extensor and ankle dorsiflexor were strongly associated with falls among day-care users. Physiotherapy should focus on the lower-extremity muscle strength to prevent falls and deterioration of physical ability among elderly persons who are partially dependent and need support.


Fish intake, plasma omega-3 polyunsaturated fatty acids, and polychlorinated dibenzo-p-dioxins (PCDDs)/polychlorinated dibenzo-furans (PCDFs) and coplanar polychlorinated biphenyls (co-PCBs) in the blood of the Japanese population.

To evaluate background exposure levels and determinants of the individual variations in the exposure to dioxins in Japan. A cross-sectional study was performed on 131 men and 122 women (aged 20-76 years), who resided in five prefectures of Japan and had no occupational exposure to dioxins. Seven polychlorinated dibenzo-p-dioxins (PCDDs), ten polychlorinated dibenzo-furans (PCDFs) and 12 polychlorinated biphenyls (PCBs), which are assigned a toxicity equivalent factor, were determined in fasting blood. Biochemical analysis of plasma and a questionnaire survey on life-style, including dietary habit, were also performed. Factors associated with the levels of dioxin-related compounds in blood were evaluated by multiple linear regression. The median of total toxicity equivalents (TEQs) in men and women was 17 and 16 pg TEQ/g lipid, respectively, with no gender difference. After adjustment for age and other covariates, plasma concentrations of eicosapentaenoic acid, a biomarker of fish intake, were found to be positively associated with blood levels of total dioxin, PCDDs, PCDFs and PCBs, all of which were expressed on a TEQ basis (P<0.01). The frequency of intake of coastal fish, such as horse mackerel, mackerel and sardine, was also associated with TEQ-based concentrations of PCDFs (P=0.03) and PCBs (P=0.08). The intake of raw fish was positively related to total dioxins (P=0.06) and PCBs (P=0.03). The level of intake of marine fish, especially raw fish and coastal varieties, may be associated with increased blood levels of dioxin-related compounds among the population. Despite high fish consumption in Japan, the body burden of dioxins in the population was not found to be higher than that in western countries.

International Archives of Occupational and Environmental Health


Minilaparotomy may be independently associated with reduction in inflammatory responses after resection of colorectal cancer.

A minilaparotomy approach (skin incision less than 7 cm) to resection of colon cancer is technically feasible, but objective data supporting its benefit are scarce. The aim of this study was to clarify whether minilaparotomy is independently associated with a reduction in the acute inflammatory response after resection of colorectal cancer. Thirty-one patients who underwent surgical resection of colorectal cancer using minilaparotomy or conventional laparotomy were included in this nonrandomized prospective study. Inflammatory responses were evaluated with serum interleukin-6 (IL-6) and C-reactive protein (CRP) levels. In both the minilaparotomy and conventional laparotomy groups, serum IL-6 and CRP levels significantly increased 24 h after the operation (1POD) compared to preoperative levels (p < 0.0001 and p < 0.0001, respectively). Median serum levels of IL-6 and CRP in the minilaparotomy group were significantly lower at 1POD versus the conventional group (p = 0.0066 and p = 0.0033, respectively). Multivariate analyses showed that a smaller increase in serum IL-6 or CRP levels at 1POD [less than 75th percentile (112.9 or 10.6 mg/ml, respectively)] was independently related to only minilaparotomy. These data in this nonrandomized trial suggest that minilaparotomy may be independently associated with reduced inflammatory responses in colorectal cancer resection.


Geographic distribution of the incidence of adult T-cell leukemia/lymphoma and other malignancies in Nagasaki Prefecture, Japan.

It remains unclear whether human T-cell lymphotropic virus type-I (HTLV-I) infection is associated with an increased risk of malignancies other than adult T-cell leukemia/lymphoma. The authors investigated the geographic distribution of the incidence of adult T-cell leukemia/lymphoma and other malignancies in Nagasaki Prefecture, Japan, where HTLV-I is endemic. The world age-standardized incidence rates of adult T-cell leukemia/lymphoma and five cancers of other sites were calculated in 15 areas, using the data from the Nagasaki Prefectural Cancer Registry (1985-97). The incidence of adult T-cell leukemia/lymphoma was found to be positively correlated with that of biliary tract cancer in men (person-years-weighted r = 0.49, P = 0.06) and liver cancer in women (r = 0.56, P = 0.03), but not with cancer of the stomach, lung or cervix uteri. The results may not support the hypothesis that HTLV-I infection is strongly associated with an increased risk of cancer of the stomach, lung or cervix uteri. The association between HTLV-I infection and cancer of the biliary tract and the possible interaction between hepatitis C virus and HTLV-I in the development of liver cancer should be evaluated by prospective cohort studies.


Comparison of Kangaroo Care and standard care: Behavioral organization, development and temperament in healthy low-birth-weight infants through one year.

To determine whether Kangaroo Care (KC) for healthy, low-birth-weight (LBW) infants can promote better behavioral and developmental outcomes. In this historical control study, 26 infants in the KC group (GA: 34.3+/-2.5 weeks, BW: 1833.9+/-167.6 g) and 27 infants in the comparison group who received the standard medical-nursing care (34.6+/-2.3 weeks, 1850.9+/-156.7 g) were analyzed by the Neonatal Behavioral Assessment Scale (NBAS) at 40 weeks of postmenstrual age, the Bayley Scales of Infant Development and the Carey's Infant Temperament Questionnaire (ITQ) at 6 and 12 months corrected ages. KC infants had significantly higher NBAS scores in Orientation, State Regulation, and Supplementary items; lower Intensity scores and higher Mood scores at 6 months on the ITQ; and higher Bayley Scales score at 12 months. KC effectively promoted neonatal behavioral organization and enhanced developmental outcome over the first year of life for LBW infants.


Difference in prognostic value between sialyl Lewis (a) and sialyl Lewis (x) antigen levels in the preoperative serum of gastric cancer patients.

Sialyl Lewis(a) (CA19-9) and sialyl Lewis(x) antigens (SLX) may play a role in tumor metastasis by serving as functional ligands in the cell adhesion system. The authors examined preoperative serum levels of CA19-9 and SLX in 218 patients who underwent resection for gastric cancer to determine their prognostic value. The patients were divided into two groups, termed the low and high antigen groups, based on a value selected as a diagnostic cutoff. Correlation between the antigen serum levels, various established clinicopathologic factors, and prognosis were studied by univariate and multivariate analysis. The disease-specific interval for high CA19-9 and SLX groups was significantly shorter than that of their respective low groups (p = 0.0024 and p < 0.0001, respectively). Patients with stage III/IV tumors who had high serum SLX levels had shorter disease-specific intervals than those with low serum levels (p = 0.0017). A Cox's regression analysis revealed a high serum SLX level as an independent factor for worse outcome. In addition, logistic regression analysis revealed that a high serum SLX level was an independent predictor for liver metastasis. In conclusion, an elevated preoperative serum SLX level was a predictor for poor outcome after resection for gastric cancer, whereas CA19-9 was not.


Increased expression of sialyl Lewisx antigen as a prognostic factor in patients with stage 0, I and II gastric cancer.

Immunohistochemically detected expression of sialyl Lewis(x) (Le(x)) antigen was analyzed in 101 stage 0-II gastric cancers to clarify its prognostic value after curative gastrectomy. Patients with a high-expression of sialyl Le(x) antigen within their tumors had shorter disease-specific intervals than those with negative- or low-expressing tumors (P<0.0001). This difference was noted particularly in stage I-B or II disease. Multivariate Cox's regression analysis revealed sialyl Le(x) antigen expression to be an independent predictor of disease-specific survival (Hazard ratio=9.10). In conclusion, the increased expression of sialyl Le(x) antigen may serve as a prognostic factor after curative surgery for stages 0-II gastric cancer.


Impact of aging on the development of HCC in post-transfusion chronic hepatitis C.

Hepatitis C virus (HCV) infection is a heterogeneous disease, the natural history of which remains controversial. There is solid evidence that chronic HCV infection is responsible for the occurrence of hepatocellular carcinoma (HCC). The aim of the current cohort study was to determine the rate of the development of HCC from the time of primary HCV infection and to assess the risk factors for the development of HCC in chronic posttransfusion hepatitis C patients. Four hundred sixty-nine patients with clinically compensated HCV, who had undergone a single blood transfusion comprised the current study cohort. Patients with other risk factors for chronic liver disease were excluded. All patients were referred to the liver center at the National Nagasaki Medical Center between December 1980 and December 1998 and were followed prospectively until the end of the analysis (June 2000). Follow-up data were obtained for 445 patients. The mean duration from HCV infection to the end of the observation was 28 years. Fifty-two patients (11.1%) progressed to HCC. The mean duration from the time of blood transfusion to the diagnosis of HCC was 31 years. Multivariate Cox regression analyses revealed age, fibrosis, duration from HCV infection to study entry, and alcohol consumption to be the independent factors affecting the development of HCC. The risk of developing HCC in patients age > or = 56 years was increased 7.8-fold compared with that in patients age < 56 years. The mean age of patients at the time of HCC diagnosis was 65 years (range, 58-79 years). At the time of diagnosis, 92% of the 52 HCC patients were age > 60 years and 38 of the HCC patients (73%) were in their 60s. There was a significantly negative correlation between the duration from HCV infection to the development of HCC and the age of the patient at the time of infection (correlation coefficient = 0.702; P < 0.0001; Y = 61.1-0.82X), indicating that the age of patients, rather than the duration of HCV infection, is more significant for HCC development in patients with posttransfusion HCV. Moreover, these data may contribute to the design of an optimal follow-up schedule for patients with posttransfusion HCV.


A nested case-control study of risk factors for adult T-cell leukemia/lymphoma among human T-cell lymphotropic virus type-I carriers in Japan.

The purpose of this study was to investigate the serological risk factors for development of adult T-cell leukemia/lymphoma (ATL) among human T-cell lymphotropic virus type-I (HTLV-I) carriers. A nested case-control study was performed. The source population comprised 23,922 subjects who had either visited the outpatient clinic or who had received annual health check-ups at the K Hospital, Nagasaki, Japan, at least once during 1985-1996 (HTLV-I seroprevalence = 16.1%). Markers of HTLV-I infection were examined in stored sera from 29 incident cases of ATL diagnosed during 1985-1997, and 158 controls matched for sex, birth year, date of sample collection, and HTLV-I seropositivity (median follow-up = 6.4 years). In exact conditional logistic regression analysis, high levels of soluble interleukin-2 receptor (> or = 500 U/ml) and high HTLV-I antibody titers (> or = 1,024) were independently associated with an increased risk of developing ATL (Odds ratio 20.5. 95% confidence interval (CI) 4.5-194 and 2.9, 95% CI 0.98-9.5, respectively). The results remained essentially unchanged when the subjects were restricted to those whose histories were followed for two years or longer. These findings indicate that high soluble interleukin-2 receptor levels and high HTLV-I antibody titers are strong predictors of ATL among carriers of HTLV-I.


Evaluation of sialyl Lewisa, sialyl Lewisx and sialyl Tn antigens expression levels as predictors of recurrence after curative surgery in node-negative colorectal cancer patients.

This study aimed to determine whether sialyl Lewis(a) (Le(a)), sialyl Lewis(x )(Le(x)), or sialyl Tn antigen expression could identify a subset of node-negative colorectal cancer patients that are at high risk for recurrence after curative surgery. Tumor tissue samples from 90 patients with node-negative colorectal cancer, who had undergone surgical resection, were analyzed immunohistochemically for the expression of each antigen. Patients were classified as having low or high antigen expression depending on whether more or less than 40% of the field showed positive staining. The main outcome measure for each variable was disease-free interval. Sialyl Le(a), sialyl Le(x), and sialyl Tn antigens were expressed in 53 (58.9%), 41 (45.6%), and 34 (37.8%) carcinomas, respectively. The median follow-up was 83.5 months. Patients with high sialyl Le(x) expression had shorter disease-free intervals than those with low sialyl Le(x) expression (P = 0.0041); the expression of sialyl Le(a) or sialyl Tn antigens did not show a significant relationship with disease-free survival. Cox's regression analysis revealed that sialyl Le(x) expression was an independent predictor for disease-free survival, separate from T factor or tumor location. High sialyl Le(x) expression may be useful in identifying a subset of node-negative colorectal cancer patients who are at high risk for recurrence.

Journal of Experimental & Clinical Cancer Research


Predictive factors for preoperative serum levels of sialyl Lewisx, sialyl Lewisa, and sialyl Tn antigens in gastric cancer patients.

Preoperative serum levels of sialyl Lewis(a) (CA19-9), sialyl Lewis(x) (SLX) and sialyl Tn (STN) antigens in 180 patients with gastric cancer were examined to establish predictive factors for serum levels of these antigens compared with carcinoembryonic antigen (CEA). The patients were divided into low and high antigen groups. Multivariate logistic regression analysis revealed the following independent predictive factors for high antigen levels [odds ratio]: liver metastasis for CA19-9 [4.40], SLX [9.90], STN [39.65] and CEA [5.14]; peritoneal dissemination for SLX [4.78] or STN [13.01]; venous invasion for CEA [3.56]; lymph node metastasis for CA19-9 [4.51]. In addition, high CA19-9 levels were independently related to lymph node metastasis in patients with stage I or II tumors. In conclusion, high serum levels of CA19-9, SLX and STN are associated with liver metastasis, while high serum levels of SLX and STN are associated with peritoneal dissemination. In addition, high serum CA19-9 levels may represent an independent predictor for lymph node metastasis.


An epidemiological study on Shigella sonnei outbreak associated with contaminated drinking water--Nagasaki, Japan, May 1998

長崎市における1998年5月の赤痢集団発生に関する疫学調査


Prognostic value of serum sialyl Lea, sialyl Lex and sialyl Tn antigens in blood from the tumor drainage vein of colorectal cancer patients.


Increased serum level of sialyl Lewisx antigen in blood from the tumor drainage vein in patients with non-polypoid growth type of colorectal cancer.

Two types of colorectal cancer with distinct morphologies have been described in recent studies: polypoid growth type (PG-type) and non-polypoid growth type (NPG-type). We hypothesize that the morphologic differences may correspond to additional biological distinctions. Ratios of sialyl Lewisa (CA 19-9), sialyl Lewisx (SLX), or carcinoembryonic antigen (CEA) in the venous blood drainage from the tumor to that of the respective antigen in the peripheral venous blood (d/p ratio) was examined in order to ascertain whether or not the ratio is correlated with either the PG-type or NPG-type colorectal tumor growth pattern. Blood samples from 118 patients with colorectal cancer were obtained from a peripheral vein and from the tumor drainage vein during surgical excision of the tumor. Statistical tests were conducted by univariate and multivariate (logistic regression) analyses. Among the cancers examined there were 17 PG-type (14.4%) and 101 NPG-type (85.6%). NPG-type cancers had a higher frequency of moderately differentiated adenocarcinoma cells and T3/T4 tumors than PG-type cancers (P<0.0001 and P<0.0001, respectively). NPG-type cancers had a more advanced stage than PG-type cancers (P=0.0007). The d/p ratio of SLX in NPG-type cancers was significantly higher than that in PG-type cancers (P=0.028). Multivariate logistic regression analysis showed that three variables, namely histologic type, T factor, and d/p ratio of SLX, were independently related to tumor growth patterns. In conclusion, NPG-type cancers are characterized by a high SLX d/p ratio, which may be at least partly responsible for a different tumor progression pattern compared to other cancer types.


Mortality and cancer incidence among a population previously exposed to environmental cadmium.

International Archives of Occupational and Environmental Health


Preoperative serum levels of sialyl Lewisa, sialyl Lewisx, and sialyl Tn antigens as prognostic markers after curative resection for colorectal cancer.

In this study, we examined the preoperative serum levels of sialyl Lewisa, sialyl LewisX, sialyl Tn, and carcinoembryonic antigen in 243 colorectal cancer patients in order to clarify the role of these antigens as prognostic factors after curative surgery. The patients were divided into two groups: low and high antigen groups (lower and higher than a selected diagnostic-based cut-off value). Patients with high serum levels of sialyl Lewisa and carcinoembryonic antigen had shorter disease-free intervals than those with low serum levels of the respective antigen, although sialyl Lewisx and sialyl Tn showed no significant differences. Multivariate analysis revealed that three independent prognostic variables, including depth of tumor invasion, lymph node metastasis, and serum sialyl Lewisa level, did prove to have value in predicting disease-free interval. In conclusion, among the four antigens examined in this study, the preoperative serum level of sialyl Lewisa is the only independent prognostic variable for recurrence after curative resection of colorectal cancer.


Significance of cadmium concentrations in blood and hair as an indicator of dose 15 years after the reduction of environmental exposure to cadmium.

To evaluate the significance of cadmium (Cd) concentrations in blood (B-Cd) and hair (H-Cd) as an indicator of dose, a cross-sectional study was performed on 40 residents in a Cd-polluted area, Nagasaki Prefecture, Japan, in 1996. In the study area, soil replacement of Cd-polluted rice fields ended in 1981. B-Cd and H-Cd were significantly higher in the study population than in the control subjects. B-Cd was positively correlated with urinary Cd (U-Cd) (Spearman r=0.50, P=0.06 for males and r=0.72, P=0.0001 for females), while H-Cd was weakly or moderately correlated with U-Cd. After adjustment for gender using logistic regression analysis, log(B-Cd) and log(U-Cd), but not log(H-Cd), were significantly associated with the prevalence of increased urinary beta2-microglobulin (P for trend <0.05). These findings suggest that B-Cd is a good indicator of cumulative dose many years after the reduction of environmental exposure to Cd. H-Cd may be weakly or moderately correlated with body burden.


Prognostic value of carcinoembryonic antigen (CEA) in tumor tissue of patients with colorectal cancer.

To establish the prognostic value of carcinoembryonic antigen (CEA) concentration in tumor tissue (T-CEA), normal colonic mucosa (N-CEA) and pre-operative serum (S-CEA), we studied 79 patients who underwent resections for colorectal cancer. The patients were separated into groups reflecting laboratory values lower or higher than a diagnostic value (S-CEA) or the median value of the entire population (T-CEA, N-CEA). A high S-CEA predicted for more advanced stage (p = 0.028), whereas no association was noted between stage and CEA concentration for T-CEA and N-CEA groups. The high S-CEA and T-CEA groups had a worse clinical outcome (p=0.0036 and p=0.024, respectively), while survival of high versus low N-CEA groups did not differ. By Cox's regression analysis, high T-CEA concentration was an independent variable for poor outcome (Hazard ratio, 3.15), while S-CEA and N-CEA were not. In conclusion, a high T-CEA concentration was the only independent predictor of poor outcome after resection for colorectal cancer.


Pre-operative serum levels of sialyl Tn antigen predict liver metastasis and poor prognosis in patients with gastric cancer.

To clarify the prognostic value of preoperative serum levels of sialyl Tn antigen (STN) for survival of gastric cancer patients. Pre-operative serum levels of STN, sialyl Lewis(a)antigen (CA19-9) and carcinoembryonic antigen (CEA) were examined in 180 patients who underwent resection of gastric cancer. Patients were divided into high and low antigen groups on the basis of a selected diagnostic-based cut-off value. Correlation between high antigen serum levels, established clinicopathologic factors and prognosis was examined by univariate and multivariate analysis. Twenty-eight patients (15.6%) were classified as high STN; 37 (20.6%) as high CA19-9; and 33 (18.3%) as high CEA. The survival time of the high STN, CA19-9 or CEA group was shorter than that of the respective low-antigen group (P<0.0001, P=0.0008 or P=0.0002, respectively). Patients with stage III/IV tumours with high STN had a shorter survival time that those with low STN (P=0.0004). Cox's regression with multiple covariates showed that high serum STN is an independent factor predicting a worse outcome in gastric cancer patients. Multiple logistic regression analysis revealed that high serum STN is an independent predictor for the development of liver metastasis. Pre-operative high serum levels of STN predict both liver metastasis and poor prognosis after resection for gastric cancer.

EJSO - European Journal of Surgical Oncology


Potential exposure to inorganic mercury in people living near a sewage sludge dumping site: urinary excretion of mercury, subjective symptoms and renal function

産業廃棄物処分場周辺地区住民の無機水銀曝露調査 尿中水銀濃度，自覚症状ならびに腎機能


Evaluation of adult T-cell leukemia/lymphoma incidence and its impact on non-Hodgkin lymphoma incidence in southwestern Japan

The incidence of adult T-cell leukemia/lymphoma (ATL) and its impact on that of total non-Hodgkin lymphoma (NHL) were evaluated in Nagasaki, an area in southwestern Japan where human T-cell lymphotropic virus type I (HTLV-I) is endemic. The first study area comprised 4 towns located on the K Islands, which had a population of 26,870 in 1990. The overall HTLV-I seroprevalence estimated from the serologic survey of 18,485 subjects was 16.2%. By using the data from the Nagasaki Prefectural Cancer Registry (NPCR) and reviewing clinical and laboratory information, we identified 40 cases of ATL and 35 cases of other NHL diagnosed between 1985 and 1995. The crude annual incidence of ATL among 100,000 HTLV-I carriers aged 30 or older was estimated at 137.7 for men and 57.4 for women, with a significant sex difference after adjustment for age (rate ratio = 2.50, 95% confidence interval 1.32-4.73). The cumulative risk from 30 to 79 years of age was estimated at approximately 6.6% for men and 2.1% for women. Among the entire population, ATL accounted for 51 to 59% of the total NHL incidence, showing the strong impact of HTLV-I infection. The second study area comprised the whole of Nagasaki Prefecture (total population in 1990 = 1.56 million). Between 1985 and 1995, 989 cases of ATL and 1,745 cases of other NHL were registered in the NPCR. The world age-standardized annual incidence rate of ATL per 100,000 persons aged 30 or older was estimated at 10.5 for men and 6.0 for women, which accounted for approximately 37 to 41% of the total NHL incidence.


A progress report of the Marshall Islands Nationwide Thyroid Study: an international cooperative scientific study

The objective of this report is to present a summary of progress of the Marshall Islands Nationwide Thyroid Study. As well known, the US atomic weapons testing program in the Pacific was conducted primarily between 1946 and 1958 in the Marshall Islands. The nuclear tests resulted in radioactive contamination of a number of atolls and resulted in exposure of Marshallese to undefined levels before our study. Little information has been paid to health consequences among residents of the nearly twenty inhibited atolls except for some information about nodular thyroid disease which was reported on by an US group. In a cooperative agreement with the Government of the Marshall Islands, between 1993 and 1997 we studied the prevalence of both thyroid nodules and thyroid cancer among 4766 Marshallese potentially exposed to radioiodines from bomb test fallout. That group represents more than 65% of the population at risk. We diagnosed 45 thyroid cancers and 1398 benign thyroid nodules. In addition, 23 study participants had been operated on prior to our study for thyroid cancer. Presently, we are developing a database of information to estimate radiation doses and planning a statistical analysis to determine if a dose-response relationship exists. These data will be important for the health promotion of exposed people all over the world including Hiroshima, Nagasaki, Semipalatinsk, Chernobyl and other locations. A timely completion is important for purpose of assisting Marshallese as well as to add the global understanding of radiation induced thyroid cancer.

The Tohoku Journal of Experimental Medicine


Human T-lymphotropic virus type-I infection, antibody titers and cause-specific mortality among atomic-bomb survivors.

Japanese Journal of Cancer Research (Cancer Science)


Coronary risk factors in acute Kawasaki disease: correlation of serum immunoglobulin levels with coronary complications


Reproducibility of urinary beta-2 microglobulin and cadmium excretion among residents in a cadmium-polluted are during a 3-year period.


High seropveralence of anti-HTLV-I antibody in rheumatoid arthritis


基本健康診査の結果と生命予後との関連に関する追跡調査

基本健康診査の結果と生命予後との関連に関する追跡調査


Prevalence of serum and salivary antibodies to HTLV-1 in Sjögren's syndrome.


Mortality among inhabitants of an HTLV-I endemic area in Japan.


Renal tubular function after reduction of environmental cadmium exposure: a ten-year follow-up.


Follow up study of renal tubular dysfunction and mortality in residents of an area polluted with cadmium.

British Journal of Industrial Medicine (Occupational and Environmental Medicine)


Water pollution by cadmium and the onset of Itai-itai disease


Association between cadmium-induced renal dysfunction and mortality: further evidence.

Our previous follow-up study, carried out from 1979 to 1989, on 256 residents of Sasu, a cadmium (Cd)-polluted area located on Tsushima Island, Nagasaki Prefecture, Japan, showed a significant relationship between urinary beta 2-microglobulin (beta 2-m) excretion and mortality in men. To investigate the association between Cd-induced renal dysfunction and mortality more precisely, 275 residents in the same area aged 40-92 years, who had participated in a health survey conducted in May 1982, were followed to February 1989. The expected number of deaths was calculated on the basis of the sex- and 5-year-age-specific mortality rates for Tsushima Island in 1985. In both men and women with urinary beta 2-m concentrations greater than 1,000 micrograms/g creatinine, observed deaths were greater than the expected. However, the P value of the difference was less than 0.05 only in women. Analysis by the Cox proportional hazards model showed that, in both men and women, serum beta 2-m and creatinine, as well as urinary total protein and beta 2-m were significantly or marginally significantly related to mortality independent of age. In men, serum beta 2-m was more strongly related to mortality than urinary beta 2-m. The results provide further evidence for the causal association between Cd-induced renal dysfunction and mortality. The present report also discusses the role played by decreased glomerular filtration rate in the excess mortality of subjects with Cd-induced renal dysfunction.


Association between renal tubular dysfunction and mortality among residents in a cadmium-polluted area, Nagasaki, Japan.

A retrospective cohort study was carried out to clarify the effect of exposure to environmental cadmium (Cd) on mortality. A total of 256 residents aged 50 years or older, living in Sasu, a Cd-polluted area in Tsushima Island in Nagasaki Prefecture, Japan, were followed from July 1979 to February 1989. The expected number of deaths calculated was based on the sex- and age- specific mortality rate in Tsushima Island in 1985. In Sasu residents of both sexes with urinary beta 2-microglobulin (beta 2-m) concentration greater than 1,000 microgram/g creatinine in 1979, observed deaths were greater than expected. However, the p value of the difference was less than 0.05 only in men. The relationships of age, mean blood pressure, urinary beta 2-m and urinary Cd concentration to mortality were examined using Cox's proportional hazards model. Urinary beta 2-m was independently and significantly related to mortality in men but not in women. The results suggest an association between Cd-induced renal tubular dysfunction and mortality.


An analysis of health related behavior using interpretive structural modeling

保健行動連鎖の可視化・認識の試み


As assessment of the acceptance of a face graph as a health educatio device

個人健康情報表示手段としての顔グラフの保健指導場面への導入の検討―保健婦と保健婦学生による評価―


Community people's preference of hand drawn face graph as a health informing device

Although the cartoon of a face is an effective device to visualize the image of numerical indices, its use is not popular among community health personnel. In the present study, we used the face graph as an aid for health informing and educating activities in the setting of a community health activity. For this purpose, we designed a special sheet to draw face by hand. By using this sheet, each person can draw his/her 'face' from one's laboratory data index under the guidance of additional lines. The acceptability of this hand drawn face was evaluated by 283 people aged 65 years and over at a health counseling session. For both men and women, a higher percentage preferred face (37% for men, 40% for women) over numeral (23% for men, 17% for women). The preference for the face graph was also observed at each of three age groups within each sex. The highest affinity to face (64%) was observed for the 14 women who reported as cataract patients.

The Tohoku Journal of Experimental Medicine


カドミウム環境汚染による健康影響に関する研究 第2報

カドミウム環境汚染による健康影響に関する研究 第2報


カドミウム環境汚染による健康影響に関する研究 第1報

カドミウム環境汚染による健康影響に関する研究 第1報


Urinary trehalase activity as an indicator of kidney injury due to environmental cadmium exposure.


Trends of incidence rate of adult T-cell leukemia/lymphoma in an HTLV-1 endemic area in Japan


Mortality rate among cadmium-exposed inhabitants was significantly higher than entire Japanese population.


カドミウム腎障害における酸塩基平衡異常

カドミウム腎障害における酸塩基平衡異常