[Show abstract][Hide abstract] ABSTRACT: Alcoholic ketosis and ketoacidosis are metabolic abnormalities often diagnosed in alcoholics in emergency departments. We attempted to identify determinants or factors associated with alcoholic ketosis.
Alcohol and alcoholism (Oxford, Oxfordshire). Supplement 08/2014;
[Show abstract][Hide abstract] ABSTRACT: Rare non-synonymous variants of TREM2 have recently been shown to be associated with Alzheimer's disease (AD) in Caucasians. We here conducted a replication study using a well-characterized Japanese sample set, comprising 2,190 late-onset AD (LOAD) cases and 2,498 controls. We genotyped 10 non-synonymous variants (Q33X, Y38C, R47H, T66M, N68K, D87N, T96K, R98W, H157Y, and L211P) of TREM2 reported by Guerreiro et al. (2013) by means of the TaqMan and dideoxy sequencing methods. Only three variants, R47H, H157Y, and L211P, were polymorphic (range of minor allele frequency [MAF], 0.0002-0.0059); however, no significant association with LOAD was observed in these variants. Considering low MAF of variants examined and our study sample size, further genetic analysis with a larger sample set is needed to firmly evaluate whether or not TREM2 is associated with LOAD in Japanese.
Journal of Alzheimer's disease: JAD 04/2014; · 4.17 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Excessive alcohol use is associated with health problems for the elderly in combination with their chronic conditions. One such complication, alcohol-related dementia (ARD) is brought about by direct or indirect ethanol intoxication, and coexisting nutritional deficiency, liver disease, cerebrovascular disease and traumatic brain injury. The elderly people with ARD have been underestimated and underdiagnosed. In these older alcoholics, atrophic changes, lacunar infarcts and deep white matter lesions of the brain are evident and are associated not only with their cognitive decline, but also with their frailty, leading to high morbidity and mortality ratio. Although lifelong abstinence can recover patients with ARD to temporally lull, aging, the severity of alcohol dependence, and the concomitant nutritional, physical and environmental factors can all impact negatively their outcome. Therefore, a comprehensive approach to lifestyle factors is recommended so that they can minimize preventable risks and maintain health status. Nursing home placement may be an appropriate treatment option for some refractory, long-term patients with ARD.
Nippon rinsho. Japanese journal of clinical medicine 04/2014; 72(4):749-56.
[Show abstract][Hide abstract] ABSTRACT: We conducted an epidemiological study to examine the associations between sleep environments and sleep habits in Japanese adolescents. The targets were students attending junior and senior high schools throughout Japan. Sample schools were selected by cluster sampling. Self‐reported anonymous questionnaires were then sent to the schools for all students to complete. A total of 99 416 adolescents responded, with an overall response rate of 64.0%. A total of 96 861 questionnaires were subjected to analysis. Associations between sleep environments (type of bed, lighting during sleep, sharing a bedroom) and sleep duration, bedtimes, wake‐up times, sleep quality, or symptoms of insomnia were examined. In total, 65.5% of the adolescents surveyed slept on a bed, and 33.0% slept on a futon laid on the floor or tatami. In total, 66.6% slept with the light off, 31.0% slept with a dim light on, and 2.0% slept with the light on. Of those surveyed, 69.3% had their own bedrooms, 17.1% shared a bedroom with one other person, 8.0% shared a bedroom with three people, and 5.0% shared a bedroom with four people or more. The factors with high odds ratios with regard to insomnia were use of a futon laid on the floor or tatami, sleeping with the light on, and not sharing a bedroom. Sleep environments are associated with insomnia. Type of bed, lighting, and sharing a bedroom should be considered as factors that affect the sleep of adolescents.
Sleep and Biological Rhythms 04/2014; 12(2). · 1.05 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Oxidation of ethanol by alcohol dehydrogenase (ADH) generates acetaldehyde (AcH), which is converted to acetate by aldehyde dehydrogenase-2 (ALDH2). Roughly 40% of East Asians are ALDH2-deficient due to an inactive enzyme encoded by the ALDH2*2 allele. ALDH2-deficient individuals have a dramatically elevated risk of esophageal cancer from alcohol consumption.
We investigated the relationship between ALDH2*2, ADH1B*2 (encoding a highly active ADH) and erythrocyte abnormalities, in a population of Japanese alcoholic men (N = 1,238).
Macrocytosis (mean corpuscular volume [MCV] ≥100 fl) and macrocytic anemia (MCV ≥100 fl and hemoglobin <13.5 g/dl) were found in 62.4 and 24.1% of the subjects, respectively. Age-adjusted daily alcohol consumption did not differ according to ADH1B and ALDH2 genotypes. However, macrocytosis and macrocytic anemia were strongly associated with the ALDH2*1/*2 genotype multivariate odds ratios (ORs; 95% confidence interval [CI] = 2.85 [1.95 to 4.18] and 3.68 [2.64 to 5.15], respectively, versus ALDH2*1/*1). In comparison with the ADH1B*1/*1 and ALDH2*1/*1 genotype combination, the ADH1B*1/*1 and ALDH2*1/*2 genotype combination and the ADH1B*2 allele and ALDH2*1/*2 genotype combination increased stepwise the ORs (95% CI) for macrocytosis (1.65 [0.92 to 2.94] and 4.07 [2.33 to 7.11], respectively, p for difference in OR = 0.015) and macrocytic anemia (2.80 [1.52 to 5.15] and 5.32 [3.29 to 8.62], respectively, p for difference in OR = 0.045). Genotype effects were more prominent on the risks of the more advanced erythrocyte abnormalities. Older age, cigarette smoking, and low body mass index independently increased the risks of the erythrocyte abnormalities. Consumption of beer, which contains folate, decreased the risks, whereas consumption of alcoholic beverages lacking folate did not.
These results suggest that the erythrocyte abnormalities in alcoholics are attributable to high AcH exposure as well as to nutritional deficiencies and may be prevented by folate.
Alcoholism Clinical and Experimental Research 03/2014; · 3.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The efficacy of disulfiram in preventing an alcoholic relapse has been controversial. The aim of our study was to assess the efficacy of supervised disulfiram for the treatment of alcohol dependence with a multi-institutional study in Japan.
In a single-blinded, randomized placebo-controlled study, we recruited 109 patients diagnosed with alcohol dependence under ICD-10 criteria. The patients were randomly allocated to 4 treatment groups, depending on whether they took disulfiram (200 mg daily) or a placebo or whether they received adjunctive therapy consisting of mailed letters which delineated and emphasized the harmful effect of alcohol and the management of alcohol craving. The proportion of abstinence among the 4 groups at 26 weeks after discharge was the primary outcome measure. The proportion of abstinence was compared with the severity of alcohol dependence and craving. Furthermore, we examined the proportion of abstinence in patients with inactive aldehyde dehydrogenase-2 (ALDH2).
There were no significant differences among the 4 groups in terms of abstinent patients or study dropouts. The ratio of abstinence was not related to the severity of alcohol dependence or the degree of alcohol craving. Patients with inactive ALDH2 significantly sustained abstinence with the use of disulfiram (p = 0.044).
Supervised oral disulfiram use followed by intervention via letters seems to be ineffective for increasing abstinence. Further studies are necessary to prove the efficacy of disulfiram for the pharmacological treatment of alcohol dependence. We indicated the effectiveness of disulfiram for the maintenance of abstinence in patients with inactive ALDH2.
Alcoholism Clinical and Experimental Research 10/2013; · 3.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In this study, we attempted to clarify the associations between various sleep disturbance symptoms and the frequency and amount of alcohol use among Japanese adolescents. This study was designed as a cross-sectional sampling survey. A self-administered questionnaire survey was administered to students enrolled in randomly selected junior and senior high schools throughout Japan. A total of 99,416 adolescents responded, and 98,867 questionnaires were subjected to analysis. The prevalence rates of sleep disturbance in the 30 days preceding the day of the survey were as follows: subjectively insufficient sleep (SIS) (boys: 37.6%, girls: 38.7%); short sleep duration (SSD) with less than 6 h of sleep (boys: 28.0%, girls: 33.0%); difficulty initiating sleep (DIS) (boys: 12.5%, girls: 14.1%); difficulty maintaining sleep (DMS) (boys: 10.1%, girls: 10.9%); and early morning awakening (EMA) (boys: 5.1%, girls: 5.0%). Adolescents reporting one or more symptoms of DIS, DMS, and EMA were classified as having insomnia, and its prevalence was 21.5%. The prevalence of each symptom of sleep disturbance increased significantly with the number of days on which alcohol was consumed in the previous 30 days and the amount of alcohol consumed per drinking session (p < 0.01). Multiple logistic regression analyses showed that the adjusted odds ratio (AOR) for each symptom of sleep disturbance, except SIS and EMA, tended to increase with the number of days on which alcohol was consumed and the amount of alcohol consumed per drinking session. The prevalence of sleep disturbance is particularly high among adolescents drinking alcohol. The risk of having each symptom of sleep disturbance, except SIS and EMA, increases with the number of days on which alcohol was consumed and the amount of alcohol consumed per drinking session. These findings reconfirm the need to eliminate underage drinking to ensure good sleep among adolescents.
[Show abstract][Hide abstract] ABSTRACT: The Kurihama Medical and Addiction Center began to conduct research and to provide medical care for alcohol-related problems in 1963, when special alcoholism treatment wards were established in Japan for the first time. At first, the provision of medical care to patients was prioritized. However, training courses for specialists were initiated in 1975, and the Department of Clinical Research was established in 1984, which led to the formation of the present management structure in which the centre's staff are shared by three departments: Medical Care, Clinical Research and Education and Information. The Department of Medical Care provides specialized treatment for alcohol use disorders and medical services for other conditions, including behavioural addictions such as internet addiction and gambling disorder, as well as dementia and other psychiatric disorders. The Departments of Clinical Research and Education and Information are engaged mainly in specialized activities related to alcohol. The Department of Clinical Research conducts research on the epidemiology of alcohol use, the effects of alcohol on health and the treatment of alcohol use disorders in Japan, in cooperation with universities and other research institutions. The Department of Education and Information fosters the human capacity to achieve the primary, secondary and tertiary prevention of alcohol-related problems and the dissemination of information on alcohol. The centre also performs alcohol-related problem prevention activities, government consultations and international collaborative research and personal exchanges, thereby functioning as a central institution for alcohol policy-based medical services and research in Japan.
[Show abstract][Hide abstract] ABSTRACT: Aims: Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B, rs1229984) and aldehyde dehydrogenase-2 (ALDH2, rs671) affect ethanol (EtOH) metabolism and susceptibility to alcoholism. Methods: We evaluated associations between ADH1B/ALDH2 genotypes and the blood EtOH levels of 805 Japanese alcoholic men in the morning after they had drunk within the previous 34 h. Results: Age-adjusted usual alcohol consumption did not differ according to ADH1B/ALDH2 genotypes. Higher blood EtOH levels persisted for longer periods in the ADH1B*1/*1 carriers (n = 246) than in the ADH1B*2 carriers (n = 559). Blood EtOH levels did not differ by ALDH2 genotype. The blood EtOH levels ≥0.3 mg/ml (criterion for drunk driving in Japanese law) were observed (40% vs. 14-17%, P < 0.0001) in a higher proportion of the ADH1B*1/*1 carriers than of the ADH1B*2 carriers after a 12.1-to-18-h interval since the last drink. Multivariate analyses showed that the EtOH levels heightened by 0.500 mg/ml in the presence of ADH1B*1*1 and by 0.248 mg/ml in the presence of cirrhosis, and lowered by 0.120 mg/ml per 10-year age increase, by 0.087 mg/ml per 10-kg body-weight increase and by 0.673 mg/ml per 10-h interval since the last drink. The odds ratio (95% confidence interval) for an EtOH level ≥0.3 mg/ml was 3.44 (2.34-5.04) in the presence of ADH1B*1/*1, 2.01 (1.28-3.14) in the presence of cirrhosis, 0.59 (0.49-0.71) per 10-year age increase, 0.80 (0.68-0.95) per 10-kg body-weight increase and 0.10 (0.07-0.15) per 10-h interval since the last drink. Conclusion: The longer-than-expected EtOH lingering in the blood of the ADH1B*1/*1 alcoholics may exacerbate alcohol-related problems, including drunk driving.
Alcohol and Alcoholism 08/2013; · 1.96 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVE: The main objective of our study was to clarify the prevalence of disorders of arousal (confusional arousals, sleepwalking, sleep terrors) and sleep-related bruxism (teeth grinding) and their associated factors among Japanese adolescents. METHODS: Our study was designed as a cross-sectional sampling survey. The targets were students attending junior and senior high schools throughout Japan. The questionnaire asked for personal data and information on lifestyle, depressive state, and sleep status including the frequency of experiencing disorders of arousal and sleep-related bruxism. RESULTS: A total of 99,416 adolescents responded. The overall response rate was 63.7%, and 98,411 questionnaires were subjected to analysis. The prevalence of disorders of arousal was 7.1% (95% confidence interval [CI], 6.9-7.3%) among boys and 7.7% (95% CI, 7.5-7.9%) among girls. The prevalence of sleep-related bruxism was 2.3% (95% CI, 2.2-2.4%) among boys and 3.0% (95% CI, 2.8-3.2%) among girls. The factors associated with disorders of arousal were the grade in school, smoking habit, alcohol consumption, naptime (min), breakfast habit, participation in club activities, sleep duration, difficulty initiating sleep, nocturnal awakening, early morning awakening, subjective sleep assessment, snoring, decrease in positive feelings, and depression (all p<.001). The factors associated with sleep-related bruxism were gender, smoking habit, nocturnal awakening, snoring, early morning awakening, decrease in positive feelings, and depressive feelings (all p<.001). CONCLUSIONS: If disorders of arousal or sleep-related bruxism are observed in an adolescent, his or her smoking habit, alcohol consumption, sleep status, and depressive state should be considered.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The presence of the less-active form of alcohol dehydrogenase-1B encoded by ADH1B*1/*1 (vs. *2 allele) and active form of aldehyde dehydrogenase-2 (ALDH2) encoded by ALDH2*1/*1 (vs. *2 allele) increases the risk of alcoholism in East Asians. METHODS: The subjects in this cross-sectional survey were 1,902 Japanese alcoholic men (≥40 years) who underwent ADH1B/ALDH2 genotyping. RESULTS: Age-adjusted daily alcohol consumption did not differ according to the ADH1B/ALDH2 genotypes. The age-adjusted odds ratios (AORs; 95% confidence interval) for liver cirrhosis (LC; n = 359, 1.58 [1.19 to 2.09]), chronic calcific pancreatitis (CP; n = 80, 2.24 [1.20 to 4.20]), and diabetes mellitus (DM; n = 383, 1.51 [1.15 to 1.99]) were higher in the ADH1B*2 allele carriers than in the ADH1B*1/*1 carriers. The AORs for LC (1.43 [1.01 to 2.02]), CP (1.68 [0.80 to 3.53]), DM (1.63 [1.15 to 2.30]), and hypertension (HT; n = 495, 1.52 [1.11 to 2.07]) were higher in the ALDH2*1/*1 carriers than in the ALDH2*1/*2 carriers. The ADH1B*2-associated AOR for LC was 2.08 (1.46 to 2.94) among those aged 40 to 59 years, but 0.89 (0.56 to 1.43) among those aged 60 years or over, and the interaction between ADH1B genotype and age on the LC risk was significant (p = 0.009). When the group with non-LC and no/mild fibrosis was used as controls, the ADH1B*2-associated AORs increased according to the severity of their liver disease: 1.67 (1.32 to 2.11) for the group with non-LC and serum type IV collagen values ≥200 ng/ml, 1.81 (1.24 to 2.63) for the group of Child-Pugh class A LC, and 3.17 (1.98 to 5.07) for the group with Child-Pugh class B/C LC. Anti-hepatitis C virus (HCV) antibody was positive in 103 patients, and the groups with a high anti-HCV antibody titer and either the ADH1B*2/*2 genotype or the ALDH2*1/*1 genotype had the highest AORs (8.83 and 4.90, respectively). The population attributable fraction (PAF) due to the ADH1B*2 allele was 29% for LC, 47% for CP, and 27% for DM, and the PAF due to the ALDH2*1/*1 genotype was 26% for LC, 34% for DM, and 30% for HT. CONCLUSIONS: The ADH1B*2 allele increased the AORs for LC, CP, and DM of the alcoholics, and the ALDH2*1/*1 genotype increased their AORs for LC, DM, and HT. HCV infection and genetic susceptibility had a synergistic effect on the AOR for LC.
Alcoholism Clinical and Experimental Research 03/2013; · 3.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The calories in alcoholic beverages consumed by alcoholics are a major energy source and a strong modifier of their body weight. Genetic polymorphisms of alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) affect susceptibility to alcoholism and may affect body weight via gene-associated differences in fuel utilization in alcoholics. METHODS: We evaluated associations between ADH1B/ALDH2 genotypes and the body weight and body mass index (BMI) of 1,301 Japanese alcoholic men at the time of their first visit to an addiction center. RESULTS: Median (25th to 75th) caloric intake in the form of alcoholic beverages was 864 (588 to 1,176) kcal/d. Age-adjusted caloric intake did not differ according to ADH1B/ALDH2 genotypes. The body weight and BMI values showed that the ADH1B*2/*2 and *1/*2 carriers (n = 939) were significantly leaner than the ADH1B*1/*1 carriers (n = 362) irrespective of age, drinking, smoking, and dietary habits. The age-adjusted body weight values of the ADH1B*2/*2, ADH1B*1/*2, and ADH1B*1/*1 carriers were 58.4 ± 0.4, 58.7 ± 0.5, and 63.6 ± 0.5 kg, respectively (ADH1B*2 vs. ADH1B*1/*1 carriers, p < 0.0001), and the corresponding BMI values were 21.0 ± 0.1, 21.0 ± 0.1, and 22.9 ± 0.2 kg/m(2) , respectively (ADH1B*2 vs. ADH1B*1/*1 carriers, p < 0.0001). No effects of inactive ALDH2 on body weight or BMI were observed. A multivariate analysis showed that BMI decreased by 0.35 per 10-year increase in age, by 1.73 in the presence of the ADH1B*2 allele, by 1.55 when the preferred beverage was whiskey, and by 0.19 per +10 cigarettes/d and that it increased by 0.10 per +22 g ethanol (EtOH)/d and by 0.41 per increase in category of frequency of milk intake (every day, occasionally, rarely, and never). The increase in BMI as alcohol consumption increased was significantly smaller in the ADH1B*2 group than in the ADH1B*1/*1 group (p = 0.002). CONCLUSIONS: ADH1B genotype was a strong determinant of body weight in the alcoholics. The more rapid EtOH elimination associated with the ADH1B*2 allele may result in less efficient utilization of EtOH as an energy source in alcoholics.
Alcoholism Clinical and Experimental Research 02/2013; · 3.42 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We conducted a survey of alcohol-dependent patients at the time of their first visit and physicians in regard to the goals of treatment of alcohol dependence. There were 99 replies from patients, and replies from physicians related to 64 of the patients' replies were also received, and in 25.0% of them it was judged possible to make reducing the amount of alcohol consumed a temporary or final goal. Having a mild drinking problem, the absence of a personality disorder or mental retardation, the presence of a strong motivation in regard to treatment, etc., were cited as reasons for the physicians' judgments. In addition, the number of diagnostic criteria of the ICD-10 for dependence syndrome that applied was shown to be significantly related to the judgments regarding treatment goals. However, as for Alcohol Dependence Scale (ADS), there was no significant relationship with the treatment goal.
Nihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence 02/2013; 48(1):64-9; quiz 70-5.
[Show abstract][Hide abstract] ABSTRACT: Since the 1990s, we have suggested the concept of pre-alcoholism which encompasses patients who have drunk a great deal of alcohol leading to alcohol related problems such as health issues, domestic violence, drunken driving and black-outs. Pre-alcoholism excludes alcohol-dependent patients who have experienced continuous drinking or withdrawal symptoms. We have treated many outpatients with pre-alcoholism for several years. Our regimen demands that the patients must be abstinent for half a year at the beginning of their treatment. After half a year they can choose whether they will continue to be abstinent or they will resume drinking with the aim of reducing their total alcohol consumption. The study clarified the character of pre-alcoholism by investigation of the patients' background and re-diagnosis of the patients based on the International Classification of Diseases, 10th Revision (ICD-10). A remarkable ratio of pre-alcoholic patients was diagnosed with alcohol dependence under ICD-10. We classified pre-alcoholic patients into two groups, one diagnosed as having ICD-10-classed alcohol dependence and the other which did not fulfill the ICD-10 diagnostic criteria of alcohol dependence, and examined the therapeutic processes of the two groups. It was shown that most pre-alcoholic patients could finally take required courses of treatment by themselves without regard to diagnosis under ICD-10, even if they chose any treatment and made alcohol related mistakes on the way. Our findings suggested that pre-alcoholic patients, a portion of whom may have exhibited mild alcohol dependence, could select drinking reduction as a primary goal of treatment after a certain period of abstinence.
Nihon Arukōru Yakubutsu Igakkai zasshi = Japanese journal of alcohol studies & drug dependence 02/2013; 48(1):39-46.
[Show abstract][Hide abstract] ABSTRACT: AIMS: The life-time drinking profiles of Japanese alcoholics have shown that gastrectomy increases susceptibility to alcoholism. We investigated the trends in gastrectomy and alcohol dehydrogenase-1B (ADH1B) and aldehyde dehydrogenase-2 (ALDH2) genotypes and their interactions in alcoholics. METHODS: This survey was conducted on 4879 Japanese alcoholic men 40 years of age or older who underwent routine gastrointestinal endoscopic screening during the period 1996-2010. ADH1B/ALDH2 genotyping was performed in 3702 patients. RESULTS: A history of gastrectomy was found in 508 (10.4%) patients. The reason for the gastrectomy was peptic ulcer in 317 patients and gastric cancer in 187 patients. The frequency of gastrectomy had gradually decreased from 13.3% in 1996-2000 to 10.5% in 2001-2005 and to 7.8% in 2006-2010 (P < 0.0001). ADH1B*1/*1 was less frequent in the gastrectomy group than in the non-gastrectomy group (age-adjusted prevalence: 20.4 vs. 27.6%, P = 0.006). ALDH2 genotype distribution did not differ between the two groups. The frequency of inactive ALDH2*1/*2 heterozygotes increased slightly from 13.0% in 1996-2000 to 14.0% in 2001-2005 and to 15.4% in 2006-2010 (P < 0.08). Two alcoholism-susceptibility genotypes, ADH1B*1/*1 and ALDH2*1/*1, modestly but significantly tended not to occur in the same individual (P = 0.026). The frequency of ADH1B*1/*1 decreased with ascending age groups. CONCLUSIONS: The high frequency of history of gastrectomy suggested that gastrectomy is still a risk factor for alcoholism, although the percentage decreased during the period. The alcoholism-susceptibility genotype ADH1B*1/*1 was less frequent in the gastrectomy group, suggesting a competitive gene-gastrectomy interaction for alcoholism. A gene-gene interaction and gene-age interactions regarding the ADH1B genotype were observed.
Alcohol and Alcoholism 01/2013; · 1.96 Impact Factor