Youichi Kurozawa

Coffee and risk of death from hepatocellular carcinoma in a large cohort study in Japan.

We examined the relation between coffee drinking and hepatocellular carcinoma (HCC) mortality in the Japan Collaborative Cohort Study for Evaluation of Cancer Risk (JACC Study). In total, 110 688 cohort members (46 399 male and 64 289 female subjects) aged 40–79 years were grouped by coffee intake into three categories: one or more cups per day, less than one cup per day and non-coffee drinkers. Cox proportional hazards model by SAS was used to obtain hazard ratio of HCC mortality for each coffee consumption categories. The hazard ratios were adjusted for age, gender, educational status, history of diabetes and liver diseases, smoking habits and alcohol. The hazard ratio of death due to HCC for drinkers of one and more cups of coffee per day, compared with non-coffee drinkers, was 0.50 (95% confidence interval 0.31–0.79), and the ratio for drinkers of less than one cup per day was 0.83 (95% confidence interval 0.54–1.25). Our data confirmed an inverse association between coffee consumption and HCC mortality.

Leptin : adiponectin ratio as an atherosclerotic index in patients with type 2 diabetes : relationship of the index to carotid intima–media thickness

To the Editor: Diabetic metabolic abnormalities induce vascular dysfunction that predisposes diabetic patients to atherosclerosis [1]. Complications of atherosclerosis cause much of the disability and most of the mortality in diabetic patients [1]. Clinical atherosclerotic manifestations in diabetes occur primarily in vascular beds such as extracranial carotid arteries and coronary arteries [1]. On the other hand, two adipocytokines, leptin and adiponectin, play important roles in the metabolic regulation of obesity and obesity-related complications [2]. In obese subjects, plasma leptin concentrations are elevated and adiponectin concentrations decreased. Consequently, it is speculated that leptin could accelerate and adiponectin restrain the development of atherosclerosis [2]. Recently, Satoh et al. [2] reported that the plasma leptin : adiponectin ratio (L : A) is correlated with pulse wave velocity values and may be a useful biomarker for atherogenesis in obese type 2 diabetic patients. However, the significance of the L : A in diabetes has still not been thoroughly investigated. Considerable research has established carotid intima– media thickness (CIMT) as a clinical surrogate marker of atherosclerosis [3]. Although pulse wave velocity values can be roughly correlated with CIMT [3], when assessing pulse wave velocity in clinical practice, confounding factors such as abnormalities of blood pressure (BP), blood flow and sympathetic tones might increase the variability of pulse wave velocity [4] that is often observed in subjects with obesity and type 2 diabetes. Also, atherosclerosis involves two different processes: atherosis and sclerosis of the arterial wall [3]. CIMT seems to reflect atherotic (structural) changes more accurately than pulse wave velocity values, whereas the latter is considered as more of a reflection of sclerotic (functional) changes [3, 5]. Type 2 diabetes accelerates both types of change, whereas hyperlipidaemia causes mostly atherotic changes [3]. In another study using CIMT measurements [6], type 2 diabetes caused atherosclerosis at a more accelerated rate than hypercholesterolaemia, suggesting an important role of CIMT as a surrogate of atherosclerosis in diabetes. It is therefore crucial to determine whether the findings of Satoh et al. [2] are replicable with regard to CIMT measurement. With these results in mind, we examined the relationship between L : A and CIMT in patients with diabetes. A total of 152 Japanese type 2 diabetic patients (73 men, 79 women; mean age=70.1±8.7 years [mean±standard deviation]), with stable conditions, and treated with diet and/or sulfonylureas, were enrolled for this study. Sixtythree subjects were treated with sulfonylureas and 89 were treated with diet only. The study was approved by the institutional ethics committee and each subject gave informed consent. Smokers were defined as current smokers. Of the smokers, 39 were men and 10 were women. Overnight fasting plasma insulin, lipid panels and blood HbA1c values were measured by the standard procedures. Plasma leptin levels were measured using a commercially available enzyme immunoassay kit (Cayman Chemical Company, Ann Arbor, MI, USA), and adiponectin levels were measured with an enzyme-linked immunosorbent assay kit (Otsuka Pharmaceutical, Tokyo, Japan). We measured BP in the right upper arm of seated patients using a standard sphygmomanometer. CIMT was determined using a Bmode ultrasound scanner (SSD-900; Aloka, Tokyo, Japan) K. Kotani (*) . K. Saiga . Y. Kurozawa Division of Health Administration and Promotion, Tottori University, 86 Nishi-cho, Yonago, 683-8503, Japan e-mail: kakotani@grape.med.tottori-u.ac.jp Tel.: +81-859-348026 Fax: +81-859-348085

The effect of interaction between hepatitis C virus and cigarette smoking on the risk of hepatocellular carcinoma.

We evaluated the interaction between hepatitis C virus (HCV) and cigarette smoking on death from hepatocellular cancer in The Japan Collaborative Cohort Study. The odds ratio of death from HCC for smoking was 9.60 (1.50–61.35) and 1.71(0.58–5.08) among anti-HCV positive and negative individuals, respectively.

Associated factors in neonatal hypoglycemic brain injury

Although associated factors are important for the occurrence of neural damage in neonatal hypoglycemia, they are not fully understood. Sixty patients with neonatal hypoglycemia were studied through a review of their medical records in Tottori University Hospital. The patients were classified into two main groups: Group I were patients who had mental retardation, developmental delay, cerebral palsy or epilepsy while Group II were those who were normal in their follow-up. Group I consisted of 12 patients while Group II consisted of 48 patients. The median gestational age was 38 weeks in Group I and 36.7 weeks in Group II. The frequencies of small for gestational age were similar in both groups. Blood glucose levels less than 15 mg/dl were more frequent in Group 1 (50.0%) than in Group 2 (14.6%) (P=0.015). Duration of hypoglycemia was longer in Group I (median, 14 h) than in Group II (median, 1.75 h) (p<0.001). The following factors were more frequent in Group I than in Group II: toxemia (33.3% and 8.3%, p=0.043), fetal distress (58.3% and 14.5%, p=0.004), an Apgar score of less than 5 at 1 min (33.3% and 6.4%, p=0.025), neonatal seizure (53.8% and 4.3%, p<0.001) and pathological jaundice (41.7% and 6.4%, p=0.006). Cranial CT or MRI revealed cerebral lesions in 8 of the 9 Group I patients in follow-up examinations. This study indicates that severe and prolonged neonatal hypoglycemia can cause cerebral lesions and other perinatal risk factors, such as hypoxia, neonatal seizure and pathological jaundice, would exacerbate hypoglycemic brain injuries.

Lymphatic vessel density in pulmonary adenocarcinoma immunohistochemically evaluated with anti-podoplanin or anti-D2-40 antibody is correlated with lymphatic invasion or lymph node metastases

In lung cancers, lymph node metastasis of cancer cells is one of the most important prognostic factors, and lymphatic vessel invasion (LVI) is very important in the stage preceding lymph node metastases. Recently, it has been reported that lymphatic vessel density (LVD) is associated with lymph node metastasis. The aim of the present study was to evaluate the relationship between LVD and LVI based on the immunohistochemical expression of podoplanin or D2‐40, which are new specific markers for lymphatic endothelium. Using 76 cases of pulmonary adenocarcinoma, the relationship between LVD and LVI, lymph node metastases, vascular endothelial growth factor C (VEGF‐C), VEGF‐D or hepatocyte growth factor (HGF) expression was investigated. LVD was significantly associated with LVI, lymph node metastases and VEGF‐D expression. LVI was also associated with lymph node metastases, histological subtype, VEGF‐C or VEGF‐D expression. High LVD, induced by VEGF‐C or VEGF‐D expression of cancer cells, is a good indicator of lymphatic metastases and LVI in pulmonary adenocarcinoma.

Liver cancer risk, coffee, and hepatitis C virus infection: a nested case–control study in Japan

We examined hepatocellular carcinoma mortality in relation to coffee consumption and anti-hepatitis C virus (HCV) antibody seropositivity in a nested case–control study involving 96 cases. The multivariate-adjusted odds ratios (95% confidence interval) for daily coffee drinkers vs non-drinkers were 0.49 (0.25–0.96), 0.31 (0.11–0.85), and 0.75 (0.29–1.92) in all cases, in HCV-positive and in HCV-negative individuals, respectively.

The Effect of Asian Dust Events on the Daily Symptoms in Yonago, Japan: A Pilot Study on Healthy Subjects

ABSTRACT The occurrence of Asian dust events is a frequent problem, with associated health issues throughout Northeast Asia. However, the effects of Asian dust on human health are not well known in Japan. The authors evaluated the association between daily symptoms and dust events in Yonago, Japan. The subjects were 54 healthy individuals who were distributed survey sheets on nasopharyngeal, ocular, respiratory, and skin symptoms, which were quantified in February 2009. The authors investigated the symptoms of the subjects on Asian dust days and control days, and compared the symptom scores with measures of suspended particulate matter (SPM), which is the indicator of Asian dust. The scores for symptoms were significantly higher on Asian dust days than on control days (p = .020). The skin symptom scores were positively correlated with the SPM level (p < .001). These results provide preliminary evidence that Asian dust influence the symptoms of healthy subjects, although the symptoms are not severe.

Risk of death due to hepatocellular carcinoma among drinkers and ex-drinkers. Univariate analysis of JACC study data.

Hazard ratios (HR) of death due to hepatocellular carcinoma (HCC) were analyzed by gender and age strata (40-59 and 60-79) among drinkers and ex-drinkers in 66,974 eligible subjects from a a large cohort of male and female subjects aged 40-79 years, based on information about several drinking related characteristics. The HR of dying from HCC for ex-drinkers was 4 to 8 times higher than for those who had never consumed alcohol at the baseline survey. When the subjects were restricted to those without history of liver disease (LD), the HR was still high for ex-drinkers among younger males, though the difference was not statistically significant. It appeared that the earlier drinking habits were established, the higher the HR, especially for younger males without LD. Among total current drinkers, the amount ingested per occasion and the cumulative amount ingested at the baseline did not show significantly increased HRs. Among subjects without LD, larger amounts ingested per occasion and larger cumulative amount seemed to have higher HRs in older male current drinkers. Frequent drinking and later age (50 to 79) at cessation of drinking were associated with higher HRs among both genders and both age strata. After restricting the analysis to subjects without LD, many of these increased HRs remained among males. The results suggested that the association between alcohol drinking history and HR of HCC differs depending on the presence of LD. Major confounders other than age and gender associated with both drinking and HCC, e.g. smoking, hepatitis virus infection, or history of diabetes, were not considered in this analysis, and the observed associations might be confounded by any of these factors. To clarify the net association between alcohol drinking and HCC, further analysis is needed to control potential confounders, including past history of liver disease, and to consider probable effect modifiers.

The relationship between skin symptoms and allergic reactions to Asian dust.

Asian dust events result from displacement of atmospheric pollutants from the Chinese and Mongolian deserts, causing associated health issues throughout Northeast Asia. We investigated the relationship between skin symptoms in Asian dust events and contact allergy to Asian dust and associated metals. Increases in atmospheric levels of heavy metals such as Ni, Al, and Fe occurred during the severe Asian dust event on March 21, 2010. We conducted a case–control study (n = 62) with patch testing to compare skin symptoms on an Asian dust day with metal allergic reactions. Skin symptoms were observed in 18/62 subjects. Nine subjects with skin symptoms (group A) and 11 without (group B) were patch tested for six metals and Asian dust particles. Metal and dust samples were applied to the subjects’ backs for 2 days and the reactions were scored according to the International Contact Dermatitis Research Group guidelines. Differences in the positive rates between the groups were analyzed. Skin reactions to ferric chloride (p = 0.015), aluminum chloride (p = 0.047), nickel sulfate (p = 0.008), and Asian dust particles (p = 0.047) were more common in group A than in group B. Skin symptoms during Asian dust events may be allergic reactions to Asian dust particle-bound metals.

Serum adiponectin levels and lifestyle factors in Japanese men

Adiponectin plays an important role in the development of various lifestyle-related diseases such as obesity, hypertension, type II diabetes mellitus, hyperlipidemia, and metabolic syndrome, leading to the development of heart and vascular diseases. However, the determinants that affect circulating adiponectin levels, including lifestyle factors, have still not been thoroughly investigated, in a general male population in particular. A total of 109 healthy Japanese male subjects (mean age, 55 ± 14 years) with constant lifestyles were enrolled. All were on no medication. Fasting serum adiponectin levels were measured with an enzyme-linked immunosorbent assay. Each subjects lifestyle was assessed by the self-administered Breslow Questionnaire (a well-established method to estimate various lifestyles) with minor modifications. Partial correlation analysis for serum adiponectin levels, after controlling age and all lifestyle factors, revealed a significant and independent negative correlation between serum adiponectin levels and body mass index (BMI) (r = −0.222, P = 0.025), and a significant and independent positive correlation between serum adiponectin levels and sleep duration (r = 0.252, P = 0.011). No significant correlations were observed between adiponectin and other lifestyle factors. These data suggest that increased BMI and shorter sleep duration may be significant independent risks for low serum adiponectin levels in healthy males. Therefore, these factors may be intervention targets to modulate adiponectin to its proper levels for the prevention of cardiovascular disorders.