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Biomedical subjects

A H Wu

Publications and source records attributed to A H Wu.

At least 19 recordsLinked to original sources

Relative weight, weight change, height, and breast cancer risk in Asian-American women.

BACKGROUND: Breast cancer incidence rates have historically been four to seven times higher in the United States than in China or Japan, although the reasons remain elusive. When Chinese, Japanese, or Filipino women migrate to the United States, their breast cancer risk rises over several generations and reaches that for white women in the United States, indicating that modifiable exposures are involved. In a previous report on this case-control study of breast cancer in Asian-American women, designed to take advantage of their diversity in risk and lifestyle, we demonstrated a sixfold gradient in risk by migration history, comparable to the international differences in breast cancer incidence rates. PURPOSE: In this analysis, we have examined the roles of adult height, adiposity, and weight change in breast cancer etiology. METHODS: A population-based, case-control study of breast cancer was conducted among women of Chinese, Japanese, and Filipino ethnicities, aged 20-55 years, living in San Francisco-Oakland (CA), Los Angeles (CA), and Oahu (HI) during the period from April 1, 1983, through June 30, 1987. We successfully interviewed 597 (70%) of 852 eligible case subjects and 966 (75%) of 1287 eligible control subjects from August 1985 through February 1989. Subjects were asked about current height, usual adult weight, and usual weight in each decade of life, excluding the most recent 3 years and any periods of pregnancy. RESULTS: Height, recent adiposity (weight in the current decade of life/height 1.5), and recent weight change (between the current and preceding decades of life) were strong predictors of breast cancer risk after adjustment was made for accepted breast cancer risk factors. Risk doubled (relative risk [RR] = 2.01; 95% confidence interval [CI] = 1.16-3.49) over the 7-inch (17.8-cm) range in height (two-sided P for trend = .003), with comparable effects in both premenopausal and postmenopausal women. Except for reduced risk in the heavy, younger women (weight/height 1.5 > 29 kg/m 1.5 and < 40 years old), risk was positively associated with usual adult adiposity. Trends in risk became more striking as adiposity in each succeeding decade of adult life was considered. Women in their 50s and in the top quintile for their age group had twice the breast cancer risk (RR = 2.13; 95% CI = 1.17-3.87) of women in the bottom quintile (two-sided P for trend = .004). Women in their 50s, above the median adiposity for their age group, and with a recent gain of more than 10 pounds had three times the risk (RR = 3.01; 95% CI = 1.45-6.25) of women below the median adiposity and with no recent weight change. Recent weight loss was consistently associated with reduced risk (RRs of approximately 0.7) relative to no recent weight change. CONCLUSIONS: Adult adiposity, weight change, and height are critical determinants of breast cancer risk. Increased adiposity and weight gain in the decade preceding diagnosis are especially influential, suggesting that excess weight may function as a late stage promoter. IMPLICATIONS: Weight maintenance and/or reduction as an adult, possibly accompanied by specific changes in diet and physical activity, may have a significant and rapid impact on breast cancer risk.

Adult

Family history of cancer and risk of lung cancer among lifetime nonsmoking women in the United States.

In a multicenter study of lung cancer in lifetime nonsmokers in the United States, 646 female lung cancer patients and 1,252 population controls were interviewed regarding history of cancer in their first-degree relatives. A 30% increased risk (95% confidence interval 0.9-1.8) was found for a history of respiratory tract cancer in parents or siblings after adjustment for exposure to environmental tobacco smoke (ETS) in adult life. Lung cancer, which represented approximately two thirds of the respiratory tract cancers, occurred more frequently in first-degree relatives of lung cancer patients than in comparable relatives of population controls (ETS-adjusted odds ratio = 1.29, 95% confidence interval 0.9-1.9). In particular, a significant threefold increased risk for lung cancer was associated with lung cancer diagnosed in mothers and sisters. The increased risk in relation to family history of lung cancer was observed among parents and siblings who were smokers as well as in those who were nonsmokers. The association with family history of lung cancer was strengthened when the analysis was restricted to adenocarcinoma of the lung (ETS-adjusted odds ratio = 1.50, 95% confidence interval 1.0-2.2). However, there was no association between family history of other cancers and risk of lung cancer in nonsmokers.

Adenocarcinoma

Menstrual and reproductive factors and risk of breast cancer in Asian-Americans.

We conducted a population-based case-control study of breast cancer among Chinese-, Japanese- and Filipino-American women in Los Angeles County Metropolitan Statistical Area (MSA), San Francisco-Oakland MSA and Oahu, Hawaii. One objective of the study was to quantify breast cancer risks in relation to menstrual and reproductive histories in migrant and US-born Asian-Americans and to establish whether the gradient of risk in Asian-Americans can be explained by these factors. Using a common study design and questionnaire in the three study areas, we successfully conducted in-person interviews with 597 Asian-American women diagnosed with incident, primary breast cancer during the period 1983-87 (70% of those eligible) and 966 population-based controls (75% of those eligible). Controls were matched to cases on age, ethnicity and area of residence. In the present analysis, which included 492 cases and 768 controls, we observed a statistically non-significant 4% reduction in risk of breast cancer with each year delay in onset of menstruation. Independent of age at menarche risk of breast cancer was lower (odds ratio; OR=0.77) among women with menstrual cycles greater than 29 days. Parous Asian-American women showed a significantly lower risk of breast cancer then nulliparous women (OR=0.54). An increasing number of livebirths and a decreasing age at first livebirth were both associated with a lower risk of breast cancer, although the effect of number of livebirths was no longer significant after adjustment for age at first livebirth. Women with a pregnancy (spontaneous or induced abortions) but no livebirth had a statistically non-significant increased risk (OR=1.84), but there was no evidence that one type of abortion was particularly harmful. A positive history of breastfeeding was associated with non-significantly lower risk of breast cancer (OR=.78). There are several notable differences in the menstrual and reproductive factors between Asian-Americans in this study and published data on US whites. US-born Asian Americans had an average age at menarche of 12.12 years-no older than has been found in comparable studies of US whites, but 1.4 years earlier than Asian women who migrated to the US. Asian-American women, particularly those born in the US and those who migrated before age 36, also had a later age at first birth and fewer livebirths than US whites. A slightly higher proportion of Asian-American women breastfed, compared with US whites. The duration of breastfeeding was similar in US-born Asians and US whites, but was longer in Asian migrants, especially those who migrated at a later age. Menstrual and reproductive factors in Asian-American women are consistent with their breast cancer rates being at least as high as in US whites, and they are. However, the effects of these menstrual and reproductive factors were small and the ORs for migration variables changed only slightly after adjustment for these menstrual and reproductive factors. These results suggest that the lower rates of breast cancer in Asians must be largely as a result of other environmental/lifestyle factors.

Adult

Once-daily aminoglycoside dosing: impact on requests and costs for therapeutic drug monitoring.

Recently, much interest has focused on the use of once-daily aminoglycosides (ODA) in the medical literature. In late 1992, we implemented a hospital-wide ODA program for adult patients at our 850-bed community-teaching hospital. In the first phase of implementation, therapeutic drug monitoring (TDM) was accomplished with the use of a random serum concentration and a nomogram that had been developed at our institution. In the second phase, serum drug concentrations were eliminated on patients with normal renal function. The fully implemented program resulted in a 40% decrease in the request for gentamicin and tobramycin serum concentrations as compared with historic ordering patterns for conventional aminoglycoside dosing regimens. In addition, the incidence of nephrotoxicity was also reduced from 3 to 5% with conventional aminoglycoside dosing, to 1.2 and 1.3% for phases 1 and 2, respectively. Furthermore, the elimination of TDM requests totaling 300 for gentamicin and 50 for tobramycin per month is expected to result in an annual institutional savings of > $100,000.

Adult

Previous lung disease and risk of lung cancer among lifetime nonsmoking women in the United States.

The authors conducted a population-based case-control study of lung cancer in nonsmoking women in five metropolitan areas of the United States between December 1, 1985, and November 30, 1990. In-person interviews were conducted with 412 lung cancer cases and 1,253 population controls, yielding information on history of nonmalignant lung diseases that were diagnosed by a physician. When lung cancer cases were compared with controls, history of any previous lung disease was associated with a significant increased risk of lung cancer (adjusted odds ratio (AOR) = 1.56, 95% confidence interval (CI) 1.2-2.0). Several lung diseases, including asthma, chronic bronchitis, pneumonia, and tuberculosis, were reported more often by lung cancer cases than by controls, and the difference was statistically significant for asthma (AOR = 1.67, 95% CI 1.1-2.5) and chronic bronchitis (AOR = 1.60, 95% CI 1.1-2.4). Since significant increased risks were observed for asthma and tuberculosis diagnosed before age 21 years, it is unlikely that reported prior lung diseases were prediagnostic manifestations of lung cancers. The increased risks associated with previous lung disease were observed for adenocarcinomas and other carcinomas of the lung; the point estimates were generally higher for the latter category. The risks associated with previous lung diseases remained unchanged after adjustment for potential confounders, including environmental tobacco smoke exposure during childhood and adult life and dietary factors.

Adenocarcinoma

Prostate cancer in relation to diet, physical activity, and body size in blacks, whites, and Asians in the United States and Canada.

BACKGROUND: International and interethnic differences in prostate cancer incidence suggest an environmental, potentially modifiable etiology for the disease. PURPOSE: We conducted a population-based case-control study of prostate cancer among blacks (very high risk), whites (high risk), and Asian-Americans (low risk) in Los Angeles, San Francisco, Hawaii, Vancouver, and Toronto. Our aim was to evaluate the roles of diet, physical activity patterns, body size, and migration characteristics on risk in these ethnic groups and to assess how much of the interethnic differences in risk might be attributed to interethnic differences in such lifestyle characteristics. METHODS: We used a common protocol and questionnaire to administer personal interviews to 1655 black, white, Chinese-American, and Japanese-American case patients diagnosed during 1987-1991 with histologically confirmed prostate carcinoma and to 1645 population-based control subjects matched to case patients by age, ethnicity, and region of residence. Sera collected from 1127 control subjects were analyzed for levels of prostate-specific antigen (PSA) to permit comparison of case patients with control subjects lacking serological evidence of prostate disease. Odds ratios were estimated using conditional logistic regression. We estimated the proportion of prostate cancer attributable to certain risk factors and the proportion of interethnic risk differences attributable to interethnic differences in risk-factor prevalence. RESULTS: A positive statistically significant association of prostate cancer risk and total fat intake was found for all ethnic groups combined. This association was attributable to energy from saturated fats; after adjusting for saturated fat, risk was associated only weakly with monounsaturated fat and was unrelated to protein, carbohydrate, polyunsaturated fat, and total food energy. Saturated fat intake was associated with higher risks for Asian-Americans than for blacks and whites. In all ethnic groups combined, the risk tended to be higher when only case patients with advanced disease were compared with control subjects with normal PSA levels. Among foreign-born Asian-Americans, risk increased independently with years of residence in North America and with saturated fat intake. Crude estimates suggest that differences in saturated fat intake account for about 10% of black-white differences and about 15% of white-Asian-American differences in prostate cancer incidence. Risk was not consistently associated with intake of any micronutrients, body mass, or physical activity patterns. CONCLUSIONS: These data support a causal role in prostate cancer for saturated fat intake but suggest that other factors are largely responsible for interethnic differences in risk.

Black or African American

Vasectomy and prostate cancer: results from a multiethnic case-control study.

BACKGROUND: Vasectomy, a widely used form of contraception, has been associated in some studies with increased prostate cancer risk. PURPOSE: We assessed this association on the basis of data collected in a large multiethnic case-control study of prostate cancer that was conducted in the United States (Los Angeles, San Francisco, and Hawaii) and Canada (Toronto and Vancouver). METHODS: In home interviews conducted with newly diagnosed prostate cancer case patients and population control subjects, we obtained information on the participants' medical history, including a history of vasectomy and the age at which the procedure was performed, as well as other potential risk factors. Blood samples were collected from control subjects only and were assayed for concentration of sex hormones and sex hormone-binding globulin. RESULTS: The present analysis was based on 1642 prostate cancer patients and 1636 control subjects. A history of vasectomy was not significantly associated with prostate cancer risk among all racial/ethnic groups combined (odds ratio [OR] = 1.1; 95% confidence interval [CI] = 0.83-1.3), whites (OR = 0.94; 95% CI = 0.69-1.3), blacks (OR = 1.0; 95% CI = 0.59-1.8), or Chinese-Americans (OR = 0.96; 95% CI = 0.42-2.2). Among Japanese-Americans, the OR was 1.8 (95% CI = 0.97-3.4), but the statistically nonsignificant elevation in risk was limited to more educated men and those with localized cancers. ORs did not vary significantly by age at vasectomy or years since vasectomy. We found a lower serum concentration of sex hormone-binding globulin and a higher ratio of dihydrotestosterone to testosterone among vasectomized control subjects than among nonvasectomized control subjects. CONCLUSIONS: The findings of this study do not support previous reports of increased prostate cancer risk associated with vasectomy. However, the altered endocrine profiles of vasectomized control subjects seen in this cross-sectional comparison warrant further evaluation in longitudinal studies.

Aged

Family history and prostate cancer risk in black, white, and Asian men in the United States and Canada.

Increased risk of prostate cancer in men with a family history of the disease has been observed consistently in epidemiologic studies. However, most studies have been confined to white men; little is known about familial aggregation of prostate cancer in populations with unusually high incidence, such as African Americans, or in populations with low incidence, such as Asian-Americans. The authors report results from a population-based case-control study of prostate cancer among blacks, whites, and Asian-Americans in the United States and Canada. Controls were matched to cases on age (5-year groups), ethnicity (black, white, Chinese-American, Japanese-American), and region of residence (Los Angeles, San Francisco, Hawaii, Vancouver, Toronto). In the combined group of participants, 5% of controls and 13% of cases reported a father, brother, or son with prostate cancer. These prevalences were somewhat lower among Asian-Americans than among blacks or whites. A positive family history was associated with a statistically significant two- to threefold increase in risk in each of the three ethnic groups. The overall odds ratio associated with such a family history, adjusted for age and ethnicity, was 2.5 (95% confidence interval 1.9-3.3). This odds ratio varied by neither ethnicity nor age of the participants. Sera from 1,087 controls were used to examine the relations between family history and serum concentrations of androgens and prostate-specific antigen. The concentrations of sex hormone-binding globulin were slightly higher in men with than without a positive family history. Prostate-specific antigen concentrations were unrelated to family history.

Aged

Automated assay of oxygen radical absorbance capacity with the COBAS FARA II.

Reactive oxygen species are of interest in biology and medicine because of evidence relating them to aging and disease processes. A relatively simple but sensitive and reliable method for quantifying the oxygen radical absorbance capacity (ORAC) of antioxidants in biological tissues has been automated for use with the COBAS FARA II centrifugal analyzer with a fluorescence-measuring attachment. In this assay, beta-phycoerythrin (beta-PE) is used as an indicator protein, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) as a peroxyl radical generator, and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) as a calibrator for antioxidant activity. This assay is unique because the reaction goes to completion so that both inhibition time and inhibition degree are considered in quantifying ORAC (micromoles of Trolox equivalent per liter or per gram of tissue). This method can be used not only for serum but also other tissue and food samples and is suitable for application to a range of nutritional and clinical conditions.

Animals

CEDIA for screening drugs of abuse in urine and the effect of adulterants.

The performance of the Microgenics CEDIA DAU assays for screening amphetamines, barbiturates, benzodiazepines, cocaine, opiates, phencylidine (PCP), and tetrahydrocannabinol (THC) was evaluated on the Boehringer Mannheim/Hitachi 717 in urine. Limits of detection ranged from 0.6 ng/mL for PCP, to 34.1 ng/mL for benzodiazepines. The average within run and total precision for these assays ranged from 1.3 to 7.3% for controls at cutoff concentrations, and control values at -25% and +25% of cutoffs. The rate separations by CEDIA between the negative and cutoff calibrators for all drugs were greater than corresponding EMIT II (Syva Co.) assays. The relative sensitivity and specificity of CEDIA as compared to EMIT II were 95.6 and 98.8%, respectively, on 13,535 urine samples. All positive samples, and those samples producing discordant results between the assays were confirmed by quantitative gas chromatography/mass spectrometry (GC/MS). Using SAMHSA cutoff limits (and including barbiturates and benzodiazepines at 300 ng/mL), the relative sensitivity and specificity of CEDIA vs. EMIT II were 96.7 and 98.8%, respectively. The overall sensitivity of CEDIA vs. GC/MS was 98.9% with 179 false positives, as compared to 96.2% with 189 false positives for EMIT II vs. GC/MS. The effect of adulterants added to urine to potentially invalidate screening results was also tested. CEDIA produced strong interferences for most drug assays in the presence of glutaraldehyde, detergent, and high concentrations of bleach and Drano. Minimal or selective interferences were seen with golden seal tea lemon juice, Visine, and low concentrations of bleach and Drano. Essentially no interference was observed with bicarbonate, sodium chloride, and vinegar.

Gas Chromatography-Mass Spectrometry

Definitive identification of an exceptionally high methanol concentration in an intoxication of a surviving infant: methanol metabolism by first-order elimination kinetics.

Intoxication by methanol was identified in a five-week-old infant suffering from moderate metabolic acidosis. The initial serum methanol at admission was 1148 mg/dL as measured by gas chromatography. The osmolal gap and formic acid concentrations were consistent with methanol intoxication. The child was treated with folic acid and a continuous ethanol infusion and survived without any apparent permanent problems. Because expected toxic symptoms did not develop in this case, and the methanol concentrations were at levels that might be deemed to be incompatible with life, blood and urine samples were assayed by a specific enzymatic assay, and by gas chromatography/mass spectrometry (GC/MS). Positive results definitively confirmed the presence of methanol. In contrast to previous reports, the elimination of methanol in this case appeared to following first-order kinetics. If hepatic ADH activity is low in neonates and young infants, another enzyme system such as catalase may be involved to explain this data. The lack of formic acid accumulation may have been due to folic acid therapy.

Acidosis

Metaanalysis in clinical chemistry: validation of cardiac troponin T as a marker for ischemic heart diseases.

Metaanalysis is a method that incorporates the pooling of previously published results to produce more statistically significant results. We used metaanalysis to examine the role of a new cardiac marker, cardiac troponin T (cTnT), in patients with ischemic heart disease. Metaanalysis of six articles and one abstract on cTnT showed that this marker was just as sensitive as creatine kinase MB isoenzyme (CK-MB) for the retrospective diagnosis of acute myocardial infarction (AMI) 12-48 h after onset but less specific. Most of these articles showed that cTnT was increased in non-AMI patients with unstable angina pectoris. In a metaanalysis of four papers, two abstracts, a letter, and an unpublished manuscript, we examined the prognostic role of cTnT in non-AMI cardiac patients. For an unfavorable endpoint defined as cardiac death, AMI, or the need for coronary artery revascularization, the results demonstrated that abnormal concentrations of cTnT were associated with a higher risk for a poor outcome than were normal concentrations of cTnT. We also compared cTnT with CK-MB for risk stratification. Metaanalysis will become an increasingly important tool for evaluating new tests as they become available.

Biomarkers

In-vitro production of ethanol in urine by fermentation.

Driving while under the influence of alcohol (DUI) can lead to serious injuries to the intoxicated driver and surrounding individuals, in addition to revocation or suspension of driving privileges. The accuracy and interpretation of the testing procedures may be compromised if an individual's urine contains sugar, and either bacteria or yeast. Under these conditions, ethanol can be produced in vitro, producing a result that may be erroneously indicative of DUI. In this study three yeast species and six bacterial species were added to a blank urine sample devoid of any alcohol or sugar. Samples were incubated at 0, 25, and 35 degrees C for 24, 48, and 144 hours in the presence of one of four different sugars. Ethanol concentrations were assayed using an enzymatic alcohol dehydrogenase assay. Results showed that when glucose was used as a substrate, all yeast species (Candida albicans, Candida parapsilosis, and Candida sp. not albicans) and three bacterial species (Klebsiella pneumoniae, Escherichia coli, and Proteus mirabilis) were capable of producing ethanol while the other three (Enterococcus sp., Staphylococcus sp. not aureus, and Pseudomonas aeruginosa) were not. The rate of ethanol production is temperature dependent and can be inhibited by storage of samples at 0 degrees C or the use of approximately 1% sodium fluoroide as an antimicrobial agent. Many of these species were also able to use other substrates (sucrose, fructose, and galactose) to produce ethanol by fermentation.

Candida

Evaluation of laboratory tests as a guide to diagnosis and therapy of myositis.

Plasma CK concentrations have been widely used as the primary muscle enzyme marker for diagnosis and progression of myositis. Recently, total CK and CK-MB serum concentrations have been compared to, and used in conjunction with, serum concentrations of aspartate aminotransferase in diagnosis of myositis. The algorithmic use of CK, AST, and aldolase plasma concentrations to diagnose and categorize patients with myopathy may be a useful method of diagnosing specific muscle disease without invasive procedures. CAIII, as a specific marker for skeletal muscle damage, may replace CK as the enzyme of choice in diagnosis and progression of myositis and other muscle disease. Additional studies are required to determine the usefulness of carbonic anhydrase for the diagnosis and assessment of myositis.

Biomarkers