Gender differences in the effect of auditory stimuli on ventricular repolarization in healthy subjects.

INTRODUCTION: Gender differences in the incidence of ventricular arrhythmias have been reported and torsade de pointes associated with long-QT syndrome (LQTS) is more common in women than men. Although auditory stimulation has been recognized as an important trigger of torsade de pointes in LQT2 patients, the normal response and gender differences in ventricular repolarization induced by auditory stimuli remained to be evaluated systematically. METHODS: Holter ECGs were recorded in 30 healthy volunteers (14 men aged 25 +/- 4 years and 16 women aged 23 +/- 2 years). They were awakened by an alarm clock at 5:00 am. The RR and QT (QTc) intervals and the T-wave amplitude were measured before and after alarm ringing. RESULTS: The morphology of the T-wave changed dynamically and transiently during awakening. The RR interval significantly decreased just after sounding of the alarm in both sexes (P < 0.0001). The QT interval changed little after the alarm ringing and was significantly longer in women than men (P < 0.0001). The QTc intervals were significantly prolonged just after alarm ringing in both sexes (P < 0.0001); QTc prolongation was significantly longer and more sustained in women than men (P < 0.0001). The T-wave amplitude decreased after the alarm and was significantly lower in women than men (P = 0.0001). CONCLUSION: Auditory stimulation abruptly and abnormally modulated the dynamics of ventricular repolarization in healthy subjects; the effect was more pronounced in women than men. This gender difference may partially account for the increased susceptibility of women with electrically unstable hearts to arrhythmogenesis.

Longevity-associated mitochondrial DNA 5178 A/C polymorphism influences effects of cigarette smoking on serum protein fraction levels in Japanese men.

Mitochondrial DNA 5178 adenine/cytosine (mt5178 A/C) polymorphism is reportedly associated with longevity and susceptibility to age-related diseases in Japanese individuals. We previously reported an association between mt5178 A/C polymorphism and serum protein fraction levels in healthy Japanese women. An association between habitual smoking and serum protein fraction levels has also been reported previously. The aim of this study was to examine whether mt5178 A/C polymorphism influenced the effects of habitual smoking on serum protein fraction levels in 321 healthy Japanese men. In mt5178C genotype men, alpha-1 and alpha-2 globulin levels were higher in smokers than in nonsmokers (P<0.001, and P=0.002, respectively). The influence of smoking on these globulin levels depended on cigarette consumption. However, in mt5178A genotype men, no significant difference was observed in alpha-1 or alpha-2 globulin levels between smokers and nonsmokers. These results suggest that longevity-associated mt5178 A/C polymorphism may influence the effects of cigarette smoking on serum protein fraction levels in healthy Japanese men.

Association of the longevity-associated mitochondrial DNA 5178 A/C polymorphism with serum protein fraction levels in healthy Japanese women.

Mitochondrial DNA 5178 adenine/cytosine (mt5178 A/C) polymorphism was reported to be associated with longevity and susceptibility to adult-onset diseases in Japanese. To examine whether mt5178 A/C genotypes are associated with serum protein fraction profiles, we genotyped 461 healthy Japanese individuals, and studied the relationship of mt5178 A/C genotypes to both proportion and levels of serum protein fraction. The mt5178 A/C was genotyped using polymerase chain reaction-restriction fragment length polymorphism method. The alpha-1, alpha-2, and beta globulin proportions in females carrying mt5178A were significantly higher than those in females carrying mt5178C (P=0.002, 0.006, and 0.008, respectively). Moreover, the alpha-1, alpha-2, and beta globulin levels in females carrying mt5178A were significantly higher than those in females carrying mt5178C (P=0.001, 0.002, 0.018, respectively). This difference in globulin fraction level between the two genotypes was more evident in premenopausal females than in postmenopausal females. However, no such difference was found in males. These results provide the first evidence that the mt5178 A/C polymorphism may influence the serum protein fraction levels of the healthy Japanese women.

Longevity-associated mitochondrial DNA 5178 A/C polymorphism modulates effects of daily drinking and cigarette consumption on serum triglyceride levels in middle-aged Japanese men.

Mitochondrial DNA 5178 adenine/cytosine (mt5178 A/C) polymorphism is one of the longevity-associated mitochondrial DNA polymorphisms. The frequency of the mt5178A genotype is significantly higher in Japanese centenarians than in the general population. We previously reported that serum high-density lipoprotein cholesterol levels were significantly higher in men with mt5178A than in those with mt5178C. However, this significant difference disappeared after adjusting for drinking frequency. To investigate the interaction between mt5178 A/C polymorphism and habitual drinking on serum lipid levels, we performed an association study in 321 healthy middle-aged Japanese men. Interaction between mt5178 A/C polymorphism and daily drinking on serum triglyceride (TG) levels was observed (P=0.019). Moreover, interaction between mt5178 A/C polymorphism and cigarette consumption on serum TG levels was also observed (P=0.022). Multiple regression analysis showed that, in men with mt5178A, daily drinking decreased TG levels (P=0.025), and cigarette consumption increased TG levels (P<0.001), while in men with mt5178C, the effects of daily drinking and cigarette consumption on TG levels were unclear. No interaction was observed on other lipid levels. Longevity-associated mitochondrial DNA 5178 A/C polymorphism thus influences the effects of daily drinking and cigarette consumption on TG levels in middle-aged Japanese men.

Effects of nutrient and food intake on calcaneous bone mass among healthy Japanese women in the predelivery and postpartum periods.

OBJECTIVE: To clarify the dietary factors affecting change in calcaneous bone mass during the predelivery and postpartum periods in healthy Japanese women. METHODS: The calcaneous bone mass was measured as the osteo sono-assessment index (OSI) using the quantitative ultrasound method in 76 Japanese women who were pregnant between February and June 2000. These women subsequently experienced normal pregnancy and labor and could be followed until the sixth month after delivery at an obstetrics and gynecology clinic center located in metropolitan Tokyo. After the intraindividual changes in the OSI during the follow-up period were determined, the relationship between the OSI or OSI change from gestation to the postpartum period and the estimates of nutrient and food intake obtained using a 140-item semiquantitative food frequency questionnaire (FFQ) were analyzed using stepwise multiple regression analysis. RESULTS: Iron intake in gestation was a significant positive correlate with the percentage change in the OSI between week 36 of gestation and day 5 after delivery (p < 0.001) and that between week 36 of gestation and month 6 after delivery (p < 0.001) (partial regression coefficient of energy-adjusted iron intake, beta = 0.493 mg/day and 0.342 mg/day, respectively). Intake of vitamin D and fruits and vegetables during gestation and/or postpartum was positively associated with the OSI change from week 36 of gestation to the postdelivery stage, whereas the OSI change was inversely related to the intake of carotene, sodium chloride, and meat in the gestation or postpartum period. CONCLUSIONS: Sufficient intake of iron, vitamin D, or fruits and vegetables may be important for the preservation of bone mass after delivery.

Clinical study on the metastasis to the eyes from breast cancer.

In our hospital, 24 patients who underwent surgery for breast cancer during 1980 to 2001 were diagnosed with metastasis to the eye. Metastasis to the choroid was found most frequently, making the choroid the most common site of metastasis. A few patients had metastasis to the orbit. Decreased visual acuity and tunnel vision were frequently found in patients who had metastasis to the choroid, and ocular floaters and blurred vision were also found in a few patients. Patients with metastasis to the orbit showed diplopia caused by ocular dyskinesia and eyelid swelling. The mean postoperative period until the diagnosis with metastasis to the eye was 3 years and 2 months, with most cases diagnosed between 20 and 40 months postoperatively, a relatively long period. We performed radiotherapy in 21 of the 24 patients, and more than half of the patients showed improvement. The mean survival period after diagnosis with metastasis to the eye was 10 months, and some of them already had recurrence to other organs such as the bones or lungs. Examination with consideration of metastasis to the eyes is required to improve the quality of life of cancer patients,.

Association of life-style with intraocular pressure in middle-aged and older Japanese residents.

PURPOSE: To evaluate the associations of several life-style-related factors with intraocular pressure (IOP). METHODS: Of a total of 649 men and women who had been examined in an annual health check-up being conducted by a general hospital in Ibaraki prefecture, Japan, 569 individuals (age range, 29-79 years) who had not undergone any medical treatment for hypertension, ocular hypertension, or glaucoma, were selected as the subjects of this study. The associations of several life-style-related factors with the IOP were evaluated by multiple regression analyses and analyses of covariance. RESULTS: Body mass index (BMI), alcohol consumption score, and cigarette consumption were found to have a significantly positive association with the IOP in men (P for trend =.002, <.001, and <.001, respectively). In women also, the BMI was positively related to the IOP (P for trend =.071). In respect to the effects of coffee consumption, it was shown that in men the mean IOP adjusted for age, the BMI, alcohol intake score, cigarette consumption, and blood pressure were significantly lower in habitual coffee drinkers than in coffee abstainers (P =.016). CONCLUSION: The results of this study suggest that the IOP level may be substantially affected by daily life-style among Japanese.

Relations of blood pressure to angiotensinogen gene T174M polymorphism and alcohol intake.

To clarify the interactive effects of alcohol intake and angiotensinogen gene codon 174 (T174M) polymorphisms on blood pressure in Japanese male workers. On the basis of data from health examinations, nutrition survey and T174M genotype analysis conducted for 185 Japanese male workers at 2000, the prevalence of high-normal blood pressure (HNBP) and hypertension were compared between the four subgroups crossed by two T174M genotype categories ('TT' type, and 'TM or MM' type) and two alcohol intake categories (less than 13.7 g per day, and 13.7 g or more per day). Furthermore, for 95 subjects who had been normotensive at 1998 among them, risk of development into HNBP or hypertension at 2000 were compared across the four subgroups. The findings showed that the HNBP prevalence adjusted for age, body mass index, smoking habits and sodium intake in 2000 was significantly (p=0.03) greater in 'TM or MM' type (57.9%) than in 'TT' type (24.9%) in subjects with 13.7 g or more of daily alcohol intake, whereas no difference in this parameter was found between the two genotypes in those with less than 13.7 g of daily alcohol intake (18.2% and 18.3%, respectively). The risk for development into HNBP at 2000 was also greatest in 'TM or MM' type with 13.7 g or more of daily alcohol intake among the four subgroups, although there were not significant differences between the four subgroups. The prevalence of hypertension or development risk for hypertension did not significantly differ between the four subgroups. Therefore, it can be seen that alcohol drinking might be specifically associated with the HNBP in M allele carriers of angiotensinogen gene T174M polymorphism.

Interrelations among smoking habits, casual blood pressure and intraocular pressure in middle and old-aged Japanese residents.

OBJECTIVES: To investigate the association of smoking habits with blood pressure (BP) and intraocular pressure (IOP), and to examine whether the smoking-BP association is related to the IOP level. METHODS: This study was conducted on the basis of a cross-sectional design using annual health check-up data during one-year between August, 1999 and August, 2000 for 611 middle and old-aged Japanese residents living in Ibaraki prefecture, Japan. RESULTS: After adjustment for age, gender, body mass index and alcohol intake score, the proportion of hypertensives, and the mean systolic and diastolic blood pressure (SBP and DBP) of the subjects without antihypertensive medications were the highest (50.4%, 129.6 mmHg and 75.9 mmHg, respectively) in the "smokers of 25 or more cigarettes per day with intraocular pressure (IOP)≥15 mmHg" of six subgroups crossed by three smoking categories (non-smokers, 1 to 24 cigarettes per day, and 25 or more cigarettes per day) and two IOP categories (less than 15 mmHg, and 15mmHg or greater). On the other hand, the adjusted proportion of hypertensives, and the adjusted mean SBP and DBP decreased with increasing smoking category in the individuals with less than 15 mmHg of the IOP (p for trend=0.028 for proportion of hypertensives 0.008 for the SBP, and 0.001 for the DBP, respectively). CONCLUSIONS: Heavy smoking may be specifically related to 'high BP accompanied by high IOP', although the BP may be inversely associated with smoking under the condition without high IOP.