Human leukocyte antigen class II DRB1*1302 allele protects against cervical cancer: At which step of multistage carcinogenesis?

We investigated the role of human leukocyte antigen (HLA) class II alleles in multistage cervical carcinogenesis. Cross-sectional analysis for HLA association with cervical cancer included 1253 Japanese women: normal cytology (NL, n = 341), cervical intraepithelial neoplasia grade 1 (CIN1, n = 505), CIN grade 2 or 3 (CIN2/3, n = 96), or invasive cervical cancer (ICC, n = 311). The HLA class II allele frequencies were compared by Fisher's exact test or the χ(2) -test. The Bonferroni adjustment corrected for multiple comparisons. Among the study subjects, 454 women with low-grade squamous intraepithelial lesion cytology were prospectively monitored by cytology and colposcopy every 3-4 months to analyze cumulative risk of CIN3 within the next 10 years in relation to HLA class II alleles. HLA class II DRB1*1302 allele frequency was similar between women with NL (11.7%) and CIN1 (11.9%), but significantly decreased to 5.2% for CIN2/3 and 5.8% for ICC (P = 0.0003). Correction for multiple testing did not change this finding. In women with low-grade squamous intraepithelial lesion cytology, the cumulative risk of CIN3 diagnosed within 10 years was significantly reduced among DRB1*1302-positive women (3.2% vs. 23.7%, P = 0.03). In conclusion, the two different types of analysis in this single study showed the protective effect of the DRB1*1302 allele against progression from CIN1 to CIN2/3.

Association between carotenoids and outcome of cervical intraepithelial neoplasia: a prospective cohort study.

BACKGROUND: It has been suggested that micronutrients such as alpha-tocopherol, retinol, lutein, cryptoxanthin, lycopene, and alpha- and beta-carotene may help in the prevention of cervical cancer. Our aim was to investigate whether serum concentrations and/or dietary intake of micronutrients influence the regression or progression of low-grade cervical abnormalities. METHODS: In a prospective cohort study of 391 patients with cervical intraepithelial neoplasia (CIN) grade 1-2 lesions, we measured serum micronutrient concentrations in addition to a self-administered questionnaire about dietary intake. We evaluated the hazard ratio (HR) adjusted for CIN grade, human papillomavirus genotype, total energy intake and smoking status. RESULTS: In non-smoking regression subjects, regression was significantly associated with serum levels of zeaxanthin/lutein (HR 1.25, 0.78-2.01, p = 0.024). This benefit was abolished in current smokers. Regression was inhibited by high serum levels of alpha-tocopherol in smokers (p = 0.042). In progression subjects, a significant protective effect against progression to CIN3 was observed in individuals with a medium level of serum beta-carotene [HR 0.28, 95 % confidence interval (CI) 0.11-0.71, p = 0.007), although any protective effect from a higher level of serum beta-carotene was weaker or abolished (HR 0.52, 95 % CI 0.24-1.13, p = 0.098). Increasing beta-carotene intake did not show a protective effect (HR 2.30, 95 % CI 0.97-5.42, p = 0.058). CONCLUSIONS: Measurements of serum levels of carotenoids suggest that regression is modulated by smoking status. Maintaining a medium serum level of beta-carotene has a protective effect for progression; however, carotene intake is not correlated with serum levels of carotenoids.

Do neutralizing antibody responses generated by human papillomavirus infections favor a better outcome of low-grade cervical lesions?

To determine the role of neutralizing antibody generated by human papillomavirus (HPV) infections, baseline levels of serum neutralizing antibodies directed against HPV 16 and cervical HPV DNA were determined in 242 unvaccinated women with low-grade cervical abnormalities, who were then monitored by cytology and colposcopy every 4 months. In women infected with HPV 16 (n = 42), abnormal cytology persisted longer in those positive for HPV 16-specific neutralizing antibodies at baseline (median time to cytological regression: 23.8 vs. 7.2 months). Progression to cervical precancer (cervical intraepithelial neoplasia grade 3) within 5 years occurred only among women carrying HPV 16-specific neutralizing antibodies (P = 0.03, log-rank test). In women infected with types other than HPV 16 (n = 200), detection of HPV 16-specific neutralizing antibodies was not correlated with disease outcome. In conclusion, development of specific neutralizing antibodies following natural HPV 16 infection did not favor a better outcome of low-grade cervical lesions induced by HPV 16 or by other types; rather, detection of neutralizing antibodies generated by current infection may reflect viral persistence and thus help identify those who are at high risk of disease progression.

HLA class II DRB1*1302 allele protects against progression to cervical intraepithelial neoplasia grade 3: a multicenter prospective cohort study.

OBJECTIVE: Genetic variations in human leukocyte antigens (HLA) class II regions may influence the risk of cervical cancer by altering the efficiency of the immune responses to human papillomavirus antigens. This prospective study was designed to evaluate the effects of HLA class II alleles on the natural course of cervical precursor lesions. METHODS: We followed a total of 454 Japanese women with cytological low-grade squamous intraepithelial lesion (LSIL) and histological cervical intraepithelial neoplasia grades 1 to 2 (CIN1-CIN2). Patients were tested for HLA class II alleles and cervical human papillomavirus DNA at the time of entry and then monitored by cytology and colposcopy every 4 months for a mean follow-up of 39.0 months. We analyzed cumulative probabilities of cytological regression to at least 2 consecutive negative Papanicolaou tests and histological progression to biopsy-positive CIN3. RESULTS: During the follow-up period, 39 lesions progressed to CIN3, and 282 lesions regressed to normal cytology. Progression to CIN3 did not occur in DRB1*1302-positive women, and this protective effect of DRB1*1302 was statistically significant (P = 0.03). Low-grade squamous intraepithelial lesion regressed to normal cytology more quickly in DRB1*1302-positive women than in DRB1*1302-negative women (median time, 8.9 months vs 14.2 months), although the difference was not statistically significant (P = 0.16). The risk of LSIL persistence or progression to CIN3 within 5 years was not affected by any other HLA class II alleles. CONCLUSION: By using a prospective study design, we demonstrated the protective effect of the DRB1*1302 allele against progression to CIN3 among Japanese women with LSIL.

Randomized crossover study of latanoprost and travoprost in eyes with open-angle glaucoma.

INTRODUCTION: To compare the intraocular pressure (IOP)-lowering effects of 0.005% latanoprost to that of 0.004% travoprost in eyes with open-angle glaucoma (OAG). METHODS: Forty-two patients with OAG who received either latanoprost or travoprost every evening for 12 weeks, and then switched to the other medication for another 12 weeks. The IOP measurements were made with a Goldmann applanation tonometer (GAT) at the baseline, and at 1, 3, 4, and 6 months after the treatment. The IOP at the untreated baseline and at the end of each treatment period was measured at 10:00, 12:00, and 16:00 hours. The central corneal thickness (CCT) was measured at each visit using an ultrasonic pachymeter. RESULTS: The mean baseline IOP was 13.9 ± 2.5 mmHg, and the CCT was 536.7 ± 30.5 µm. Latanoprost reduced the IOP by 2.5 ± 1.7 mmHg and travoprost by 2.6 ± 1.5 mmHg from the baseline (p = 0.6807). The CCT decreased significantly to 531.9 ± 30.3 at 3 months (p = 0.0160) and to 529.4 ± 30.5 µm at 6 months (p = 0.0002) after the therapy. The decrease was significantly greater in eyes after travoprost (p = 0.0049). CONCLUSIONS: Travoprost has similar effect as latanoprost in reducing the IOP in glaucoma patients with relatively low IOPs. The use of prostaglandin analogs can decrease the CCT, and this change should be considered when the IOPs obtained by GAT are analyzed.

Subsequent risks for cervical precancer and cancer in women with low-grade squamous intraepithelial lesions unconfirmed by colposcopy-directed biopsy: results from a multicenter, prospective, cohort study.

OBJECTIVE: To investigate the natural course of low-grade squamous intraepithelial lesions (LSILs) that cannot be histologically confirmed by colposcopy-directed biopsy. METHODS: In a multicenter, prospective, cohort study of Japanese women with LSILs, we analyzed the follow-up data from 64 women who had a negative biopsy result at the initial colposcopy (biopsy-negative LSIL) in comparison with those from 479 women who had a histologic diagnosis of cervical intraepithelial neoplasia grade 1 (LSIL/CIN1). Patients were monitored by cytology and colposcopy every 4 months for a mean follow-up period of 39.0 months, with cytologic regression defined as two consecutive negative smears and normal colposcopy. RESULTS: In women with biopsy-negative LSILs, there were no cases of CIN3 or worse (CIN3+) diagnosed within 2 years; the difference in the 2-year risk of CIN3+ between the two groups was marginally significant (0 vs. 5.5%; P = 0.07). The cumulative probability of cytologic regression within 12 months was much higher in the biopsy-negative LSIL group (71.2 vs. 48.6%; P = 0.0001). The percentage of women positive for high-risk human papillomaviruses (hrHPVs) was significantly lower in the biopsy-negative LSIL group than in the LSIL/CIN1 group (62.1 vs. 78.4%; P = 0.01); however, the 12-month regression rate of biopsy-negative LSIL was similar between hrHPV-positive and -negative women (67.3 vs. 74.4%, P = 0.73). CONCLUSION: In women with biopsy-negative LSILs, the risk of CIN3+ diagnosed within 2 years was low; furthermore, approximately 70% underwent cytologic regression within 12 months, regardless of HPV testing results. Biopsy-negative LSILs may represent regressing lesions rather than lesions missed by colposcopy.

Predicting the progression of cervical precursor lesions by human papillomavirus genotyping: a prospective cohort study.

Only a subset of cervical precursor lesions progress to cervical cancer and because of the lack of the predictive markers, it cannot be ascertained which lesions will progress or not. To estimate the risk of disease progression associated with human papillomavirus (HPV) genotypes, we followed 570 Japanese women with cytological LSIL (low-grade squamous intraepithelial lesion) and histological CIN (cervical intraepithelial neoplasia) grade 1-2 lesions (479 CIN 1; 91 CIN 2) at 3 to 4 month intervals for a mean follow-up period of 39.1 months. At entry, we detected HPV DNA in cervical samples by polymerase chain reaction-based methodology. Over the period of follow-up period, 46 lesions progressed to CIN 3 while 362 regressed to normal cytology. Women with multiple HPV infections were more likely to have persistent lesions (hazard ratio [HR] for regression, 0.65; 95% confidence interval [CI], 0.42-1.02; p = 0.07); however, multiple infections did not increase the risk of progression (HR for progression, 1.04; 95% CI, 0.37-2.94; p = 0.94). After adjusting for CIN grade and women's age, HRs for progression to CIN 3 (vs. women with low-risk types or negative for HPV DNA) varied markedly by HPV genotype: type 16 (11.1, 95% CI: 1.39-88.3); 18 (14.1, 0.65-306); 31 (24.7, 2.51-243); 33 (20.3, 1.78-231); 35 (13.7, 0.75-251); 52 (11.6, 1.45-93.3); 58 (8.85, 1.01-77.6); other high-risk types (4.04, 0.47-34.7). HPV 45 was not detected in our study subjects. The cumulative probability of CIN 3 within 5 years was 20.5% for HPV 16, 18, 31, 33, 35, 52 and 58; 6.0% for other high-risk types; 1.7% for low-risk types (p = 0.0001). In conclusion, type-specific HPV testing for women with LSIL/CIN 1-2 lesions is useful for identifying populations at increased or decreased risk of disease progression.

Cigarette smoking and other lifestyle factors in relation to the risk of pancreatic cancer death: a prospective cohort study in Japan.

OBJECTIVE: To examine the association of smoking and lifestyle factors with pancreatic cancer death in the prospective design. METHODS: Mortality from pancreatic cancer in regard to smoking, body mass index, physical activity, and alcohol, coffee and green tea intake, was studied in a prospective cohort of 30,826 inhabitants in Takayama, Japan. In 1992, each subject completed a self-administered questionnaire on demographic information, smoking, drinking habits, diet, exercise and medical histories. The response rate was 85.3%. RESULTS: From 1992 to 1999, 33 men and 19 women died due to pancreatic cancer. Hazard ratios and 95% confidence intervals were determined using Cox proportional hazards models. Women who were defined as current smokers at baseline had significant and increased risk of pancreatic cancer death after adjustment for age, body mass index and history of diabetes mellitus (Hazard ratio: 4.77, 95% confidence intervals: 1.58-14.4). There were significant positive associations of pancreatic cancer death with the years of smoking and the number of cigarettes consumed daily in women in a dose-dependent manner. Current smokers indicated a non-significant risk increase in men (Hazard ratio: 3.81, 95% confidence intervals: 0.88-16.6). Body mass index, physical activity, and alcohol, coffee and green tea intake were not significantly associated with pancreatic cancer death. CONCLUSIONS: These data suggested that smoking increases the risk of death from pancreatic cancer in Japanese women.

Prevalence of tinnitus in community-dwelling Japanese adults.

BACKGROUND: Several studies have reported the prevalence of tinnitus among general populations; however, most of these studies were conducted in Europe or the United States. We estimated the prevalence of tinnitus among the general adult population in Japan. METHODS: The subjects were participants in the Takayama Study, a population-based cohort study. In 2002, a total of 14 423 adults (6450 men and 7973 women) aged 45 to 79 years responded to a self-administered questionnaire that inquired about history of tinnitus, which was defined as episodes lasting longer than 5 minutes, excluding those occurring immediately after noise exposure. Respondents were also asked about the loudness and severity of tinnitus. RESULTS: Overall, 11.9% of the subjects reported having tinnitus; the percentage was somewhat higher among men (13.2%) than women (10.8%). The prevalence of tinnitus increased with age in both sexes. Approximately 0.4% of the overall population reported that tinnitus had a severe effect on their ability to lead a normal life. Medical history of hypertension or ischemic heart diseases, use of steroid or antihypertensive medication, and employment as a factory worker or machine operator were associated with tinnitus status in both men and women. CONCLUSIONS: Tinnitus is relatively common in Japan. Although the use of various definitions of tinnitus in different studies makes it difficult to compare prevalence among populations, the present prevalence estimate was similar to those in studies in Europe and the United States.

Tobacco smoking and regression of low-grade cervical abnormalities.

The role of tobacco smoking in the multistage carcinogenesis at the cervix is not fully understood because of a paucity of prospective data. To assess the relationship between smoking and spontaneous regression of cervical precursor lesions, a total of 516 women with low-grade squamous intraepithelial lesion (LSIL) were monitored by cytology and colposcopy every 4 months. Probability of LSIL regression within 2 years was analyzed in relation to smoking behaviors, with regression defined as at least two consecutive negative Pap smears and normal colposcopy. Women's age, initial biopsy results, and human papillomavirus (HPV) genotypes were included in the multivariate models for adjustments. Our study subjects included 258 never-smokers and 258 smokers (179 current and 79 former smokers). During a mean follow-up time of 39.8 months, 320 lesions regressed to normal cytology. Probability of regression within 2 years was significantly lower in smokers than in never-smokers (55.0%vs 68.8%, P = 0.004). The risk of LSIL persistence increased with smoking intensity and duration and with younger age at starting smoking (P = 0.003, P < 0.001, and P = 0.03, respectively). Smokers had twice as high a risk of persistent HPV infection compared to never-smokers (odds ratio, 2.50; 95% confidence interval, 1.30-4.81; P = 0.006). In young women, passive smoking since childhood reduced probability of regression within 2 years (56.7%vs 85.9%, P < 0.001). Further adjustments for a wide range of cervical cancer risk factors did not change the findings. In conclusion, tobacco smoking may interfere with regression of cervical precursor lesions. Childhood exposure to second-hand smoke may increase a risk of persistent cervical abnormalities among young women.

Consumption of coffee, green tea, oolong tea, black tea, chocolate snacks and the caffeine content in relation to risk of diabetes in Japanese men and women.

Although the inverse association between coffee consumption and risk of diabetes has been reported numerous times, the role of caffeine intake in this association has remained unclear. We evaluated the consumption of coffee and other beverages and food containing caffeine in relation to the incidence of diabetes. The study participants were 5897 men and 7643 women in a community-based cohort in Takayama, Japan. Consumption of coffee, green tea, oolong tea, black tea and chocolate snacks were measured with a semi-quantitative FFQ in 1992. At the follow-up survey in 2002, the development of diabetes and the time of diagnosis were reported. To assess the association, age, smoking status, BMI, physical activity, education in years, alcohol consumption, total energy intake, fat intake and women's menopausal status were adjusted. Among men who consumed one cup per month to six cups per week and among those who consumed one cup per d or more, the associated hazard ratios were 0.69 (95 % CI 0.50, 0.97) and 0.69 (95 % CI 0.49, 0.98) compared with those who drank little to no coffee, with a P value for trend of 0.32. The hazard ratios for women with the same coffee consumption patterns were 1.08 (95 % CI 0.74, 1.60) and 0.70 (95 % CI 0.44, 1.12), with a P value for trend of 0.03. The association between estimated total caffeine intake and risk of diabetes was insignificant both among men and among women. The results imply that coffee consumption decreased the risk of developing diabetes. The protective effect may exist aside from the influence of caffeine intake.

Fruit and vegetable intake and mortality from cardiovascular disease are inversely associated in Japanese women but not in men.

Some epidemiological studies undertaken in Western countries have demonstrated that high intake of fruit and vegetables results in decreased risk of cardiovascular disease (CVD). The objective of this study was to examine the hypothesis that high intake of fruit and vegetables lowers CVD mortality in a population-based cohort of Japanese subjects. In 1992, fruit and vegetable intake was assessed in 13,355 men and 15,724 women in Takayama, Gifu, Japan using a validated FFQ. During the follow-up (1992-99), 200 men and 184 women died from CVD. For women, the highest quartile of vegetable intake compared with the lowest was marginally significant and inversely associated with CVD mortality after adjusting for total energy, age, and nondietary and dietary covariates [hazard ratio (HR) = 0.62; 95% CI, 0.36-1.08; P-trend = 0.007]. An inverse trend with borderline significance was also observed in fruit intake, excluding CVD deaths in the first 2 y of this study, after adjusting for the above-mentioned covariates (HR = 0.83; 95% CI, 0.51-1.34; P-trend = 0.10). In men, CVD death was not associated with fruit (HR = 1.16; 95% Cl, 0.77-1.74; P-trend = 0.61) and vegetable (HR = 0.81, 95% CI: 0.49-1.34; P-trend = 0.47) intake. These data suggest that higher intake of vegetables is associated with reduced risk of death from CVD for women.

Soy isoflavone intake is not associated with the development of cedar pollinosis in adults.

Although soy isoflavone has been suggested to have both immune-enhancing and immune-suppressive effects, the effects of soy isoflavone intake on allergic disorders are unclear. A cross-sectional study indicated that a high intake of soy isoflavone is associated with a decreased risk of allergic rhinitis. We aimed to prospectively examine the relationship between soy isoflavone intake and risk of cedar pollinosis, the most common seasonal allergic rhinitis in Japan. The study was conducted in a population-based cohort of Japanese men and women. Each subject's usual diet, including soy isoflavone intake, was determined with the use of a validated FFQ in 1992. In 2002, a total of 11,229 persons who were 35-69 y old and had no history of cancer or allergic diseases at the baseline responded to a follow-up questionnaire asking about 4 symptoms related to cedar pollinosis. Cox hazard regression model was used to determine the association between soy isoflavone intake and the risk of cedar pollinosis. During the 10-y follow-up, 931 of these subjects reported that they had cedar pollinosis. There was no significant association between soy isoflavone intake and risk of cedar pollinosis in men and women after controlling for covariates. For the highest compared with the lowest quartile of soy isoflavone intake, hazard ratios were 1.07 (95% CI: 0.81-1.42) in men and 0.89 (95% CI: 0.68-1.15) in women. These data did not support an association between soy isoflavone intake and risk of cedar pollinosis.

Smoking and risk of cedar pollinosis in Japanese men and women.

BACKGROUND: Pollinosis induced by the cedar pollen antigen is the most common seasonal allergic reaction in Japan. We aimed to examine the relationship between smoking and risk of cedar pollinosis in a population-based cohort of the Japanese. METHODS: Study subjects were 12,221 men and women from the Takayama Study cohort who were 35-69 years old at enrollment in 1992. A follow-up survey in 2002 was used to obtain information about four symptoms related to cedar pollinosis. RESULTS: A total of 1,000 subjects had cedar pollinosis during the 10-year follow-up. As compared with those who had never smoked, current smokers at the baseline were at a significantly decreased risk of cedar pollinosis after controlling for covariates in men (hazard ratio [HR]: 0.64, 95% CI: 0.50-0.83) as well as in women (HR: 0.64, 95% CI: 0.47-0.88). There was a significant dose-response relationship between the risk of cedar pollinosis and the number of cigarettes smoked each day as well as with the number of years an individual had smoked. A significant risk reduction was observed among men and women who had continued to smoke cigarettes during the follow-up period in comparison with those who had never smoked. There was no risk increase for former smokers at the baseline as well as for those who quit smoking during the follow-up. CONCLUSIONS: Some components of tobacco may protect against cedar pollinosis. Our finding could provide clues about therapeutic strategies for protection against cedar pollinosis.

Rationality/anti-emotionality personality and dietary habits in a community population in Japan.

BACKGROUND: There are no strong and consistent predictors of dietary habits although some associations have been shown with psychological factors. The purpose of the present study was to examine the relationships between the rationality and anti-emotionality (R/A) personality and dietary consumption in a Japanese community. METHODS: The Takayama study is a community-based cohort study on diet and cancer in Gifu, Japan, and was initiated on September 1, 1992. Cross-sectional analyses were conducted on dietary and lifestyle data. The consumption of 169 food and beverage items was measured along with portion size by using a food frequency questionnaire. Questions regarding the R/A-personality scale and lifestyle habits were included in the questionnaire. The participants were 28077 adults (13082 males and 14995 females) aged 35 years and over. RESULTS: Both males and females with high R/A-personality scores (i.e., high degree of rational thought and emotional repression) consumed more soy products, green and yellow vegetables, other vegetables, and seaweed than the other participants. Males with high R/A-personality scores drank fewer alcoholic beverages, and females with high scores were found to snack less on sweet and salty foods than the other participants. Males with high R/A-personality scores showed higher consumption of meat and dairy products, and females with high scores showed higher consumption of fish, shellfish, and eggs than those with low R/A-personality scores. CONCLUSION: The R/A-personality scale may differentiate dietary habits in males and females in a Japanese community.

Self-reported diabetes mellitus and risk of mortality from all causes, cardiovascular disease, and cancer in Takayama: a population-based prospective cohort study in Japan.

BACKGROUND: Diabetes mellitus has been reported to be a major risk factor for cardiovascular disease (CVD), and higher risk of CVD among women than that among men has been observed in many studies. Further, the association of diabetes with increasing risk of cancer has also been reported. Well-designed studies conducted among men and women in the general Japanese population remain scarce. METHODS: Our cohort consisted of 13355 men and 15724 women residing in Takayama, Japan, in 1992. At the baseline, the subjects reported diabetes in a questionnaire. Any deaths occurring in the cohort until 1999 were noted by using data from the Office of the National Vital Statistics. The risk of mortality was separately assessed for men and women by using a Cox proportional hazard model after adjusting for age; smoking status; body mass index (BMI); physical activity; years of education; history of hypertension; and intake of total energy, vegetables, fat, and alcohol. RESULTS: Diabetes significantly increased the risk of mortality from all causes [hazard ratio (HR): 1.35, 95% confidence interval (CI): 1.11-1.64] and from coronary heart disease (CHD) (HR: 2.96, 95% CI: 1.59-5.50) among men, and that from all causes (HR: 1.74, 95% CI: 1.34-2.26) and cancer (HR: 1.88, 95% CI: 1.16-3.05) among women. Diabetes was not significantly associated with mortality from CHD among women. CONCLUSION: The findings suggest that diabetes increases the risk of mortality from CVD among men and that from cancer among women. The absence of increased risk of mortality from CHD among women may suggest a particular pattern in the Japanese population.

Prospective cohort study of body mass index in adolescence and death from stomach cancer in Japan.

We investigated the association between body mass index (BMI) values and the risk of death from stomach cancer later in life. From 1992 to 2000, 28 443 participants (13 211 men and 15 232 women) were followed, and 129 deaths from stomach cancer (86 men and 43 women) occurred. BMI (BMI at the baseline) and BMI(20y) (BMI at age 20 years) were obtained by questionnaire at the beginning of the study. Men in the middle and highest tertiles of BMI(20y) had a higher risk of death from stomach cancer than those in the lowest tertile (after controlling for covariates, hazard ratio [HR] = 2.73 with 95% confidence interval [CI] 1.26-5.89 for the middle tertile; HR = 2.15 with 95% CI 0.97-4.73 for the highest tertile), although there was no significant trend (P = 0.30). Likewise, women in the middle and highest tertiles of BMI(20y) had an increased risk of death from stomach cancer (HR = 5.17 with 95% CI 1.50-17.87 for the middle tertile; HR = 4.22 with 95% CI 1.18-15.05 for the highest tertile; P for trend = 0.05). The analysis of BMI at the baseline did not show a significant relationship with the risk of death from stomach cancer. These results suggest that a high BMI(20y) is associated with an increased risk of death from stomach cancer.

Long-term therapeutic outcome of acute primary angle closure in Japanese.

PURPOSE: To investigate the long-term clinical course of acute primary angle closure (APAC) and acute primary angle-closure glaucoma (APACG) in Japanese patients. METHODS: We retrospectively reviewed our records of 66 consecutive APAC or APACG eyes observed between February 1992 and December 2003 (mean follow-up, 42.1 months). Immediately after the diagnosis, all patients had received similar medications to halt the acute attack. Subsequently, laser iridotomy or surgical peripheral iridectomy and/or laser iridoplasty were conducted. If intraocular pressure (IOP) control was poor under maximum tolerable ocular hypotensive agents, trabeculectomy with adjunctive mitomycin C (MMC) was undertaken. RESULTS: After laser therapy, the probability of success, defined as an IOP of <21 mmHg with or without medications, was 81.2% +/- 6.2%. In the ten eyes that were trabeculectomized, the probability of success based on the same criterion was 40.0% +/- 29.7%. Multivariate analysis revealed that the degree of synechial angle closure (P = 0.029) and the preexistence of chronic glaucomatous optic neuropathy (P = 0.015) significantly influenced the need for subsequent filtering surgery. CONCLUSIONS: Without the intervention of filtering surgery, 84.6% of eyes with APAC or APACG maintained IOP control with or without antiglaucoma medications. However, APAC and APACG eyes that eventually received trabeculectomy were predisposed to an uncontrollable IOP, even with the intraoperative application of MMC. The severity of APAC or APACG in Japanese may be affected by an underlying creeping angle closure.

Sodium intake and risk of death from stroke in Japanese men and women.

BACKGROUND AND PURPOSE: Despite the evidence for a positive association of dietary salt and blood pressure, the few prospective studies that have assessed the association between dietary salt and stroke have reported inconsistent results. The purpose of this study was to examine the relation between sodium intake and death from stroke in a population-based cohort of Japanese men and women. METHODS: In 1992, usual diet including sodium intake was determined in 13 355 men and 15 724 women in Takayama City, Gifu, with the use of a validated food frequency questionnaire. RESULTS: There were 269 stroke deaths (137 men and 132 women) between baseline and 1999. In men, the highest compared with the lowest tertile of sodium intake was significantly positively associated with death from total stroke after controlling for covariates (hazard ratio [HR]), 2.33; 95% CI, 1.23 to 4.45). Significantly positive associations were also observed between sodium intake and death from ischemic stroke (HR, 3.22; 95% CI, 1.22 to 8.53) as well as death from intracerebral hemorrhage (HR, 3.85; 95% CI, 1.16 to 12.7). A positive association between sodium intake and death from stroke in women was suggested, although the associations for total stroke and ischemic stroke were of borderline significance (HR, 1.70; 95% CI, 0.96 to 3.02 and HR, 2.10; 95% CI, 0.96 to 4.62, respectively). CONCLUSIONS: These prospective data support the hypothesis that dietary salt increases the risk of death from stroke.

The impact of changes in marital status on the mortality of elderly Japanese.

PURPOSE: To assess the impact of changes in marital status on the mortality of elderly Japanese men and women. METHODS: In a baseline survey conducted in 1992, 2039 male and 1466 female residents in Takayama City, Gifu, who were married and aged 65 years or over responded to a detailed health and lifestyle questionnaire. Information regarding deaths of subjects and their spouses, the causes of death, and whether the subjects and spouses moved away from the city between 1992 and 1999 was obtained from the National Vital Statistics and the residential registers of the city. A proportional hazard model was used including marital status as time- varying independent variable. RESULTS: During the study period, six men and two women became separated/divorced and 151 men and 448 women became widowed. Widowhood was not significantly associated with mortality in men. Duration of widowhood was significantly inversely associated with mortality in women (p = 0.04). A significant decreased hazard ratio (=0.40, p = 0.04) was observed for women widowed for 3 years or more. CONCLUSIONS: We found no evidence indicating that widowed men and women have an increased mortality rate. Instead, the data suggested a decreased mortality rate among long-term widowed women.