Cohort profile: the Asia Pacific Cohort Studies Collaboration.
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Biomedical subjects
Publications and source records attributed to W H Pan.
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BACKGROUND: Few prospective data from the Asia-Pacific region are available relating body mass index (BMI) to the risks of stroke and ischaemic heart disease (IHD). Our objective was to assess the age-, sex-, and region-specific associations of BMI with cardiovascular disease using individual participant data from prospective studies in the Asia-Pacific region. METHODS: Studies were identified from literature searches, proceedings of meetings, and personal communication. All studies had at least 5000 person-years of follow-up. Hazard ratios were calculated from Cox models, stratified by sex and cohort, and adjusted for age at risk and smoking. The first 3 years of follow-up were excluded in order to reduce confounding due to disease at baseline. RESULTS: A total of 33 cohort studies, including 310 283 participants, contributed 2 148 354 person-years of follow-up, during which 3332 stroke and 2073 IHD events were observed. There were continuous positive associations between baseline BMI and the risks of ischaemic stroke, haemorrhagic stroke, and IHD, with each 2 kg/m(2) lower BMI associated a 12% (95% CI: 9, 15%) lower risk of ischaemic stroke, 8% (95% CI: 4, 12%) lower risk in haemorrhagic stroke, and 11% (95% CI: 9, 13%) lower risk of IHD. The strengths of all associations were strongly age dependent, and there was no significant difference between Asian and Australasian cohorts. CONCLUSIONS: This overview provides the most reliable estimates to date of the associations between BMI and cardiovascular disease in the Asia-Pacific region, and the first direct comparisons within the region. Continuous relationships of approximately equal strength are evident in both Asian and Australasian populations. These results indicate considerable potential for cardiovascular disease reduction with population-wide lowering of BMI.
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Assessment of usual dietary intake of a population is essential to understand the nutrition status of the population. Methods like 24-hour dietary recall and food records are commonly used for this task. However, within-individual variation exists in the food record data. Methods considering measurement errors have been used to evaluate the association between nutrient intakes and diseases. Few have been devoted to estimating the distribution of usual daily intakes. This paper proposes applying the formulation of the overdispersed exponential family to estimate the distribution of usual nutrient intake and applies the adjustments developed by Liu to reduce the variance of the distribution. The proposed method has the advantages of working on the original scale of data and implementation convenience. The adjustment of the variance is carried out by dividing the variance into within-individual variance and among-individual variance. The adjusted variance, then, is used to estimate the distribution of the usual daily intake. Sampling weights are considered in all the steps, except the estimation of the ratio of within to among variance. The data for this study are from the Nutritional and Health Survey in Taiwan conducted between 1993 and 1996 (NAHSIT, 1993-1996). An independent external set of data for people aged between 18 and 28 years (49 males and 20 females) is used to estimate the ratio of within to among individual variance. Due to the availability of data in estimating the ratio of within to among individual variance, 430 males and 422 females in the NAHSIT sample are used to estimate the distribution of usual daily intakes for people aged between 18 and 28 in Taiwan. The distribution also allows us to estimate the proportion of people who do not meet the recommended daily nutrient allowance (RDNA). The results show that the intakes of calcium and vitamin E of this group of people fall far below RDNA.
AIMS: To study the extent and determinants of undiagnosed diabetes mellitus (DM) in Taiwanese subjects with impaired fasting glycemia (IFG) defined by the newly proposed WHO criteria. METHODS: Oral glucose tolerance tests were carried out for 306 IFG subjects identified from 6632 adult participants of two large scale community-based studies: Nutrition and Health Survey in Taiwan (1993-1996) and the Cardiovascular Disease Two-township Study (1994-1997). Similar protocols were used in these two studies to collect data on glycemic status, anthropometric measurements, and other data used in the present study. RESULTS: Subjects with IFG had a non-trivial undiagnosed diabetes mellitus rate (30% in men and 42% in women) and a high rate of glucose intolerance and undiagnosed DM combined (75% in men and 86% in women). Women with IFG had a 1.6 fold higher risk (p = 0.04) for undiagnosed DM and a 2.1 fold higher risk (p = 0.01) for glucose intolerance and DM when compared to men. There were more women than men with an elevated body mass index in undiagnosed DM patients. Among IFG subjects, undiagnosed DM patients were significantly (p < 0.05) older, more centrally obese and shorter than their normal IFG counterparts, irrespective of gender. In men, height was independent of age and waist circumference in predicting undiagnosed DM (p = 0.037). CONCLUSIONS: A high proportion of impaired glucose tolerance and undiagnosed DM was found in subjects with IFG. Its public health impact should not be overlooked. Central obesity, female sex, and short stature were associated with undiagnosed DM status in IFG subjects.
A rapid liquid chromatography-electrospray mass spectrometry (LC-ES-MS) method with in vivo microdialysis for the determination of free-form of cocaine (COC) in rat brain has been developed. A C18 column and a gradient elution were employed for the separation. The [M+H]+ (m/z=304) and a fragmented ion (m/z=182) were detected using positive ion mode detection. Selective ion monitoring was utilized for quantitative measurement. The linearity of this assay was good ranging from 0.01 to 1.0 microM (r2=0.999). The inter- and intra-day precisions showed relative standard deviations ranging from 1.0% to 3.3% and 1.0% to 3.6%, respectively. In addition, the detection of one COC metabolite, benzoylecgonine (BE), by this assay was also investigated. The linearity, precision, and detection limit associated with this method for BE were determined. The application of this newly developed method was demonstrated by examining the pharmacokinetics of COC in rat brain.
Although ribozymes offer tremendous potential for posttranscriptionally controlling expression of targeted genes, their utility is often limited by the accessibility of the targeted regions within the RNA transcripts. Here we describe a method that identifies RNA regions that are accessible to oligonucleotides. Based on this selection protocol, we show that construction of hammerhead ribozymes targeted to the identified regions results in catalytic activities that are consistently and substantially greater than those of ribozymes designed on the basis of computer modeling. Identification of accessible sites should also be widely applicable to design of antisense oligonucleotides and DNAzymes.
The objective of this paper is to describe hypertension status in Taiwan using data from the Nutrition and Health Survey in Taiwan (NAHSIT) 1993-1996, which adopted a clustered stratified multistage sampling scheme. A total of 4838 males and 4876 females aged 4 years and above were interviewed and examined corresponding to a response rate of 74%. Almost all of them (97.5%) had blood pressures measured. The results show that the mean blood pressure of adult males was higher than that of adult females below 45 years of age. After that, the pattern was reversed. When defined by JNC IV criteria (SBP/DBP > or = 160/95 mm Hg or taking antihypertensive drugs), the prevalence was 13% in adult males (> or = 19 years) and 12% in adult females. When defined by JNC VI criteria (SBP/DBP > or = 140/90 mm Hg or taking antihypertensive drugs), the prevalence was 26% in adult males and 19% in adult females. The prevalence in the mountainous area, was the highest among the seven survey strata. Under the JNC IV definition, 43% males and 53% females with hypertension knew their disease status, 31% of males and 45% of females took medicine for it, and 15% of males and 22% of females had their blood pressure under control. Percentages of awareness, treatment, and control were much lower with the JNC V definition, which was introduced toward the end of survey period. People in metropolitan areas had the highest rates of awareness, treatment, control, and compliance to medication.
The occurrence of asthma and allergy are related to lifestyle factors, and dietary pattern may be one of the contributing factors. To examine the possible association between dietary intake and the prevalence of asthma and allergic rhinitis in teenagers. In a population-based cross-sectional survey, the relationship was sought between food frequency and physician-diagnosed asthma and allergic rhinitis in 1166 adolescents aged 13-17. The prevalence was 4.0% for asthma and 12.4% for rhinitis. Living in an urbanized area was a significant predictor of asthma and rhinitis. In univariate analysis, higher frequencies of oily fish, butcher's meat, liver and deep-fried foods were associated with asthma. Relevant food frequency variables were dichotomized at the 75th percentile for multivariate logistic regression analysis, which included adjustment for two levels of urbanization. Asthma was associated with intakes of liver (OR = 2.32, 95%CI 1.11-4.80), deep-fried foods (OR = 2.13, 95%CI 1.06-4.30) and butcher's meat (OR 1.84, 95%CI 0.89-3.80). In a similar analysis, allergic rhinitis was associated with liver (OR = 1.67, 95%CI 1.06-2.63). No protective effect was demonstrated for any of the food items examined. Protein-rich and fat-rich foods of animal origin were associated with a higher prevalence of asthma in teenagers.
BACKGROUND: The occurrence of asthma may be associated with dietary factors. OBJECTIVE: To examine the association between nutrient intake and physician-diagnosed asthma and allergic rhinitis. METHODS: A stratified, multiple-staged sampling design was used to select study areas, in which household interviews were carried out to gather information on health status and 24-h food recall. Data from 1166 adolescents, 13-17 years of age, were analysed. RESULTS: In univariate analysis, total calorie and energy-adjusted fat intake were associated with the prevalence of asthma, whereas vitamin A and vitamin C intake showed negative association with asthma. Multivariate logistic regression was used to adjust for sex and levels of urbanization; intake of saturated fats was associated with increased risk (OR = 2.02 for an increase of one SD, 95%CI 1.40-2.90), while monounsaturated fats were inversely related to asthma (OR = 0.65 for an increase of one SD, 95%CI 0.43-0.99). Vitamin C intake in the lowest quartile was associated with elevated risk for asthma with marginal significance (OR = 1.81, 95%CI 0.88-3.71, P = 0.10). None of the nutritional factors was associated with allergic rhinitis. CONCLUSION: Results from this cross-sectional survey suggest that saturated and monounsaturated fats may have different effects on airway inflammation.
OBJECTIVE: To evaluate the prevalence of hyperuricemia in Taiwan. METHODS: A multi-stage stratified sampling scheme was used in Nutrition and Health Survey, which was conducted in Taiwan between 1993 and 96. Complete biochemical and questionnaire data for 2754 males and 2953 females aged 4 years and older were included in the analysis. The colorimetric enzymatic method was used to measure plasma uric acid in fasting blood samples. Information on self-reported, physician-diagnosed gout was also obtained. RESULTS: The uric acid values of males were found to reach a peak between the ages of 13 and 18 and decrease slightly after 18. The uric acid values of females were stable before the age of 18, decreasing slightly between 19 and 44 years, and increasing in the mid to older age groups (> or = 45 years). Twenty-six percent of adult males (> or = 19 years) and 22% of older males (> or = 45 years) either had hyperuricemia (serum uric acid > 458.0 microM or 7.7 mg/dl) or were taking medication for it. Seventeen percent of adult females and 23% of older females either had hyperuricemia (serum uric acid > 392.57 microM or 6.6 mg/dl) or were taking medication for it. Both adult males and females in mountainous areas, who were primarily aboriginal, had the highest prevalence of hyperuricemia (> 50%) among the 7 survey areas. Mean body mass index (BMI), alcohol consumption, and prevalence of gout were among the highest in mountainous people compared to all included in the study. Multivariate analysis showed that mountainous area, age and BMI are important factors associated with hyperuricemia in males, whereas mountainous area, Class II townships, and BMI are the factors associated with hyperuricemia in females. CONCLUSIONS: We found a high prevalence of hyperuricemia in Han Chinese in Taiwan despite a lack both of obesity and high alcohol consumption. Mountainous people (mainly aborigines) in Taiwan have an even higher prevalence of hyperuricemia, which cannot be completely explained by obesity and alcohol consumption. Genetic components and other environmental factors may have contributed to this pattern of hyperuricemia.
BACKGROUND AND PURPOSE: In outcome analyses of clinical trials and mortality follow-up studies, the underlying cause of death (UCOD) is commonly assigned either by official coders or by a panel of physicians. We evaluated the validity of UCOD assigned by official coders by comparison with the assignments of a panel of physicians who reviewed the available medical records of the deceased. METHODS: The comparisons focused on deaths occurring from October 1995 through June 1998 in a series of residents in a veterans home. Because of limited resources, only the first 104 deaths that occurred during the study period were included. Agreement rate, sensitivity, specificity, and kappa statistics were calculated to assess the consistency of coder versus physician panel assignment of UCOD by selected main causes of death. For 32 of the 104 deaths, the panel concluded that the information obtained from medical records was insufficient to determine the UCOD, and the following analyses were confined to the other 72 deaths. RESULTS: For the 72 deaths considered by the panel to have sufficient information to determine UCOD, all four physicians agreed on a single UCOD in 50 (69%) cases, while three or four agreed in 66 (92%) cases. A consensus was reached in cases with disagreement. The two procedures completely agreed in 40 (56%) of the deaths. For general category UCOD, the kappa value was high for cancer (0.83) and cardiovascular disease (CVD, 0.73) but only moderate for pulmonary disease (PD, 0.60). When the UCOD assigned by the panel was used as the gold standard, official coders showed relatively low sensitivity for correct determination of UCOD in cases of CVD (0.76) compared with cancer (0.86) and PD (0.80). CONCLUSIONS: Given the high inter-physician consistency and the relatively low sensitivity of official coders in assigning CVD as the UCOD, we conclude that the use of clinical review panels would provide more accurate UCOD assignments for use in outcome analyses in mortality follow-up studies and clinical trials in Taiwan.
BACKGROUND AND PURPOSE: The significance of isolated systolic hypertension (ISH) has been well documented, particularly in the elderly. However, isolated diastolic hypertension (IDH) has not been formally recognized as a unique hypertension entity. This study compared the ages of onset and characteristics of ISH and IDH. METHODS: The Cardiovascular Disease Risk Factors Two-Township Study (CVDFACTS) is an ongoing longitudinal study of the risk factors for and pathogenesis of cardiovascular disease in two Taiwanese townships, Chu-Dung (a Hakka community) and Pu-Tzu (a Fukienese community); participating patients were included in our study. Among the 3,357 subjects who were aged at least 20 years, free of hypertension, and had complete data at baseline, 2,374 subjects were followed. The average duration of follow-up was 3.23 years and the follow-up rate was 71%. Data regarding smoking, alcohol consumption, health and socioeconomic background, blood pressure, and body mass index were collected. Clinical and hemostatic profiles were assessed. RESULTS: ISH (systolic blood pressure, SBP > or = 140 mmHg and diastolic blood pressure, DBP < or = 90 mmHg) incidence increased with age in general (men: 0 per 1,000 person-years at age 20-34 yr, 1.9 at age 35-49, 14.3 at age 50-64, 40.9 at age 65-74, and 73.3 at age 75+ yr; women: 0 per 1,000 person-yr at age 20-34 yr, 3.6 at age 35-49, 17.8 at age 50-64, 64.9 9 at age 65-74, and 33.5 at age 75+ yr), but peak incidence of IDH (DBP > or = 90 mmHg and SBP < or = 140 mmHg) occurred between 35 and 49 years (men: 8.9 per 1,000 person-yr at age 20-34 yr, 14.5 at age 35-49, 12.3 at age 50-64, 2.7 at age 65-74, and 0 at age 75+ yr; women: 1.7 per 1,000 person-yr at age 20-34, 4.2 at age 35-49, 3.7 at age 50-64, 0 at age 65-74, and 0 at age 75+ yr). Significant predictors for ISH were older age (men: hazard ratio, HR = 8.25 at 45-64 yr and HR = 22.91 at 65+ yr; women: HR = 34.11 at 45-64 yr and HR = 97.98 at 65+ yr), diabetes (HR = 2.57) and elevated fibrinogen (HR = 1.49) in men, and shorter clotting time in women (HR = 1.23). Significant predictors for IDH were elevated body mass index (men: HR = 4.03; women: HR = 7.4), and higher glucose (HR = 1.46) and uric acid concentrations (HR = 1.94) in men. CONCLUSIONS: The results of this study indicate that ISH and IDH have different age incidence patterns and predictors, and suggest that the pathogenesis of ISH and IDH may be different.
Previous studies of nasopharyngeal carcinoma (NPC) have found elevated risks with higher consumption of salted fish and preserved foods, particularly during childhood. These foods can contain high levels of nitrosamines; however, most studies have not estimated exposure to nitrosamines directly. We conducted a case-control study in Taiwan to evaluate dietary intakes and NPC risk. A total of 375 cases (99% response rate) and 327 controls (88% response rate) were interviewed about their diet as an adult and at age 10 using a food-frequency questionnaire. We interviewed mothers of participants about their child's diet at age 10, age 3 and during weaning and the mother's diet while she was breast-feeding. Mothers of 96 cases and 120 controls were interviewed. Nitrosamine and nitrite levels were assigned to 66 foods based on published values. Intake of nitrosamines and nitrite as an adult was not associated with risk of NPC. High intakes of nitrosamines and nitrite during childhood and weaning were associated with increased risks of NPC for foods other than soy products. Adjusted odds ratios for the highest quartile were 2.2 [95% confidence interval (CI) 0.8-5.6] for age 10, 2.6 (95% CI 1.0-7.0) for age 3 and 3.9 (95% CI 1.4-10.4) for weaning diet. Intakes of nitrite and nitrosamines from soybean products during childhood and weaning were inversely associated with risk. Soybeans contain known inhibitors of nitrosation, and thus may explain the inverse association we observed. Our results suggest that nitrosamine and nitrite intake during childhood may play a role in the development of NPC.
There are many evidences suggest that ascorbate in the extracellular space can affect glutamate concentration in the rat's brain. In this report, we studied how ascorbate in microdialysis perfusion medium affected glutamate level at the striatum in freely-moving rats. Three perfusion mediums were used: 0, 250, and 400 microM of ascorbate in perfusion medium. The extracellular basal concentrations of glutamate were determined to be 1.29+/-0.52 microM for the no ascorbate group, 0.86+/-0.35 microM for the low ascorbate group and 4.76+/-1.48 microM for the high ascorbate group. By using 400 microM of ascorbate in a perfusion medium, we found that the extracellular basal concentration of glutamate significantly increased and its in vivo recovery significantly decreased. This indicated that ascorbate concentration in a perfusion medium was important and must be carefully considered while using microdialysis technique to monitor glutamate concentration in vivo.
A genetic linkage study of young-onset hypertension was performed on data from 59 nucleus families of Han Chinese residing in Taiwan. Thirty seven microsatellite markers near 18 hypertension candidate genes were genotyped. In a nonparametric identity-by-descent sibpair analysis, a positive linkage signal (defined as P<0.05) was found for four microsatellite markers, viz., D1S1612 (P=0.0162), D1S547 (P=0.0263), D8S 1145 (P= 0.0284), and D17S2193 (P=0.0256), which were located near genes for atrial natriuretic peptide (NPPA)/glucose transporter 5 (SLC2A5), angiotensinogen (AGT), lipoprotein lipase (LPL), and angiotensin-conveting enzyme (DCP1), respectively. Marker D5S1480 located near beta-2-adrenergic receptor (ADRB2) had a borderline P value (P=0.0785) for the positive signal. Comprehensive genotyping with further markers in these regions is underway to confirm whether these genes are linked to young-onset hypertension.
To investigate the regulatory effects of somatodendritic D2 receptors on the terminal's extracellular dopamine (DA) concentration, a D2 antagonist (eticlopride) was infused directly into the ventral tegmental area via a microdialysis probe in chloral hydrate-anesthetized rats. Extracellular DA changes in both the nucleus accumbens (N ACC) and the medial prefrontal cortex (mPFC) were monitored. Infusion of 10.0 fM eticlopride had no effect on DA in the mPFC (110.2 +/- 10.0% of baseline) but significantly increased DA in the N ACC (150.1 +/- 11.7%). Infusion of a higher dose of eticlopride (100.0 or 1,000.0 fM) significantly augmented the DA in the mPFC (121.1 +/- 7.6 and 180.7 +/- 25.8%, respectively) but surprisingly had no effect on DA in the N ACC (111.5 +/- 7.3 and 104.1 +/- 8.7%, respectively). To further investigate whether the bluntness of DA increase in the N ACC was due to DA receptor activation in the mPFC, eticlopride or SCH23390 was infused into the mPFC prior to and during intrategmental eticlopride infusion, and the change of DA in the N ACC was simultaneously monitored. During intra-mPFC 1.0 nM eticlopride infusion but not during 10.0 nM SCH23390 administration (95.5 +/- 6.1%), intrategmental 1,000.0 fM eticlopride infusion could further elevate DA in the N ACC (130.0 +/- 4.6%). Our results indicated that (1) the mesolimbic and the mesocortical pathways were under tonic inhibition by somatodendritic D2 receptors; (2) the DA concentration in the N ACC first increased and then returned to baseline while the intrategmental infusion dose of eticlopride increased; and (3) the bluntness of DA increase in the N ACC resulted from the D2 receptor activation in the mPFC.
BACKGROUND AND PURPOSE: Cerebrovascular disease was the leading cause of death in Taiwan from 1963 to 1982. Deaths due to stroke now rank second only to cancer, with more deaths resulting from strokes than from any other single pathology. It is important to understand stroke prognosis among elderly stroke survivors, with respect to survival and attendant predictive factors, because aged population in Taiwan is growing rapidly. The aim of the present study was to discern factors affecting survival in stroke patients from a nationally representative elderly sample. METHODS: A total of 99 stroke survivors, from a representative national sample of elders aged >/=65 years on December 31, 1988, whose strokes occurred in the period 1989-1993, were followed for mortality until July 1, 1995. Personal data were gathered through home interviews conducted by well-trained community nurses, and mortality data were obtained from the national census office by using identification card numbers. Cox proportional hazards regression analysis and the stepwise technique were used to search for important prognostic factors of survival. RESULTS: Women experienced a higher mortality rate (139.8 per 1000 person-years) than men (126.4 per 1000 person-years), as age-adjusted for World Health Organization world-population figures. Stroke patients who received continuous treatment for diabetes experienced mortality risks similar to those of patients without diabetes and much lower risks than those with discontinuous diabetes treatment. Cognitive impairment was also an independent predictor of survival (relative risk 2.69, P<0.05). In addition, patients with both cognitive and mobility impairments had a 2- to 3-fold greater risk of mortality than those with only a single abnormality. CONCLUSIONS: This first report on the various prognostic factors related to survival of elderly stroke patients in Taiwan's Chinese population emphasized the benefit of continuous diabetes treatment in improving survival chances. These stroke patients should also be monitored for cognitive and mobility impairments and undergo rehabilitation.