Amino acid concentrations in cerebrospinal fluid in children with acute lymphoblastic leukemia undergoing chemotherapy.

Cerebrospinal fluid (CSF) amino acid concentrations were measured in 45 children with acute lymphoblastic leukemia (ALL). Central nervous system (CNS) disease was absent in 34 and present in 11 (Groups L and M, respectively) at diagnosis. Thirty-two otherwise healthy children with febrile convulsions were studied for comparison. Results from this study show that glutamine levels at Day 0 were significantly higher in patients than in controls. Patients in Group M had elevated glutamine levels compared to Group L. In comparison, at Day 14, concentrations of glutamine and asparagine decreased, while glutamic acid amounts increased significantly in Group L. Glutamine levels fell at Day 42 in Group M, which may have resulted from more intensive treatment. From this study we hypothesise that higher baseline glutamine levels are indicative of a greater risk for CNS leukemia. Large-scale prospective trials are required to confirm increased baseline CSF glutamine levels in ALL patients, to identify glutamine as a marker for CNS disease and to clarify underlying mechanisms regulating glutamine in ALL.

Tea consumption: fluid intake and bladder cancer risk in Southern Taiwan.

OBJECTIVES: To determine whether tea consumption and intake of other beverages increases bladder cancer risk. METHODS: A case-control study was conducted in Kaohsiung, Taiwan between August 1996 and June 1997. Index patients studied were consecutive patients with histologically confirmed, newly diagnosed bladder cancer in two major hospitals. For each patient, 4 controls were selected from patients with non-neoplastic and nonurologic diseases undergoing surgical operations in the same hospital and individually matched by sex, age, and date of admission. Using a structured questionnaire, a trained interviewer interviewed 40 patients and 160 controls. Conditional logistic regression analysis adjusting for ethnicity, family history, and smoking status and matching variables were used to estimate the odds ratio (OR) and 95% confidence interval (CI). RESULTS: Tea consumption overall was associated with increased bladder cancer risk (OR 3.29, 95% CI 1.34 to 8.05). Compared with non-tea drinkers, the odds ratios of bladder cancer for oolong tea drinkers was 3.00 (95% CI 1.20 to 7.47); for non-oolong tea drinkers (black and/or other green tea), it was 14.86 (95% CI 2.13 to 103.83). The risk was greater among those who began to drink tea before age 40 (OR 9.50, 95% CI 2.39 to 37.75) and those who had been drinking tea for more than 30 years (OR 17.75, 95% CI 3.00 to 105.17). Coffee, tap water, and alcohol consumption were associated with a slightly increased risk, and both soy juice and rice juice consumption were associated with reduced risk; none of these odds ratio estimates were statistically significant, however. CONCLUSIONS: Our results suggest that tea consumption is associated with an increased risk of bladder cancer.

An MTP inhibitor that normalizes atherogenic lipoprotein levels in WHHL rabbits.

Patients with abetalipoproteinemia, a disease caused by defects in the microsomal triglyceride transfer protein (MTP), do not produce apolipoprotein B-containing lipoproteins. It was hypothesized that small molecule inhibitors of MTP would prevent the assembly and secretion of these atherogenic lipoproteins. To test this hypothesis, two compounds identified in a high-throughput screen for MTP inhibitors were used to direct the synthesis of a highly potent MTP inhibitor. This molecule (compound 9) inhibited the production of lipoprotein particles in rodent models and normalized plasma lipoprotein levels in Watanabe-heritable hyperlipidemic (WHHL) rabbits, which are a model for human homozygous familial hypercholesterolemia. These results suggest that compound 9, or derivatives thereof, has potential applications for the therapeutic lowering of atherogenic lipoprotein levels in humans.

Cancer mortality and residence near petrochemical industries in Taiwan.

An ecologic study design was used to investigate the relationship between cancer risks and residence in communities adjacent to petrochemical industrial counties (PICs). Directly age-adjusted mortality rates for cancer during 1982-1991 among 16 counties characterized by a heavy concentration of petrochemical industries were compared to rates among 16 matched counties with similar concentration of nonpetrochemical manufacturing industries, urbanization level, and demographic characteristics. An excess rate for liver cancer among males was found in the so-called PICs. The correlation could not be explained by confounding variables such as urbanization, socioeconomic class, or employment in nonpetrochemical industries. No other increased cancer risks were found to be associated with residence near petrochemical industries.

Effects of occupational dust exposure on the respiratory health of Portland cement workers.

The object of this study was to assess the relationship between occupational Portland cement dust exposure and respiratory health. Respiratory symptoms and ventilatory function were studied in a group of 591 male Portland cement workers employed in four cement plants. The prevalence of chronic respiratory symptoms was higher in exposed than in control workers. The exposed group had a significantly lower mean forced vital capacity (FVC), forced expiratory volume at 1 s (FEV1), and forced expiratory flows after exhalation of 50% and 75% of the vital capacity (FEF50, FEF75) than the control group. The data suggest that occupational exposure to Portland cement dust may lead to higher prevalence of chronic respiratory symptoms and the reduction of ventilatory capacity.

A cohort study on mortality and exposure to polychlorinated biphenyls.

In 1979, an outbreak of food poisoning ("Yu-Cheng") occurred in Central Taiwan, ROC, involving more than 2000 people. The event was caused by ingestion of rice oil contaminated with polychlorinated derivatives of biphenyls, dibenzofurans, and quaterphenyls. A retrospective cohort study on mortality was undertaken, and possible long-term health effects in the affected individuals were studied. The mortality experience of 1940 victims (929 males, 1011 females) between 1980 and 1991 was compared with the expected numbers, which were calculated from national and local mortality rates. By the end of 1991, 102 deaths were identified, thus producing a standardized mortality ratio (SMR) of overall mortality of 0.99 for males and 1.34 for females. Total cancer mortality was lower than in each comparison group. Mortality from liver diseases was elevated significantly (SMR = 3.22), especially during the first 3 y after the food-poisoning event (SMR = 10.76). Increased clinical severity of polychlorinated biphenyl intoxication was associated with increased mortality from all causes and from liver diseases. In summary, there was a positive association between mortality and intoxication dose, and severe polychlorinated biphenyl poisoning acutely affected mainly the liver. A continued follow-up of this cohort would be valuable in the study of long-term health effects of polychlorinated biphenyl poisoning.

Assessment of postpartum time-dependent disease risk in case-control studies: an application for examining age-specific effect estimates.

Among subjects who have experienced a biological event, such as menarche, menopause or a delivery, one cannot distinguish the effects of time since the event from age at the event due to the linear dependency among these time variables and age at study ('current age'). This is a well-known problem that also exists in the determination of the short- and long-term influence of childbirth on subsequent disease risk, since one must take into account in the analysis both current age and age at delivery. We describe an approach to assess in case-control studies the effect of a full-term pregnancy on time-dependent disease risk by including nulliparous women in the analysis and considering current age as a modifier of the effect of age at delivery. One then uses current age-specific odds ratio estimates that compare uniparous to nulliparous women to examine whether the relative rate of disease varies over time after a delivery. Analytic options include stratified analysis and modelling with interaction terms for unconditional or conditional logistic regression analysis. As an example, we have applied this analysis to a large case-control study that utilized record linkage between the Cancer Registry and the Fertility Registry of Sweden and that documented a transient increase in breast cancer risk after a childbirth, followed by a long-term reduction in this risk.

A case-control study of oral cancer in Changhua County, Taiwan.

Forty oral cancer patients identified consecutively in Changhua Christian Hospital between 1990 and 1992 were compared with 160 population-based controls, matched for sex, age, area of residence, and educational background. Betel quid chewing was positively associated with the risk of oral cancer with adjusted odds ratio of 58.4 (95% CI: 7.6-447.6). The greater the number of years of chewing betel quid, the higher the risk of oral cancer; the adjusted odds rations were 12.9, 93.7 and 397.5 for < 21, 21-40, and > 40 years of betel chewing as compared with the non-users. The risk also increased with the quantity chewed per day; the odds ratios for those chewing < 10, 10-20 and > 20 quids/day were 26.4, 51.2 and 275.6, respectively. These odds ratio estimates were all statistically significantly different from the null value of unity.

Dual effect of parity on breast cancer risk.

This study examined whether breast cancer risk increased for a short period after childbirth, but decreased after a longer period of time. Data from an international case-control study on breast cancer conducted in the 1960s were used to study the modifying effect of age at enrolment on the relationship between parity and breast cancer risk, comparing first uniparous with nulliparous women, and then biparous versus uniparous women. The statistical analysis was performed by modelling through multiple logistic regression, adjusting for study site, age at menarche, menopausal status and obesity index. Comparing uniparous with nulliparous women, an early age at birth seems to be protective for all periods after birth, whereas a late age at birth imparts a higher risk than nulliparity in the period immediately after birth, which declines with the passage of time. The modification effect by age was not apparent when biparous women with different age at second birth were compared with uniparous women. The results support the hypothesis that pregnancy oestrogens impart a transient increase of maternal breast cancer risk when the full-term pregnancy occurs late in a woman's life.

Prevalence and characteristics of areca nut chewers among junior high school students in Changhua county, Taiwan.

Some studies indicate that betel quid and its ingredients chewing can produce cell mutagenicity and tumorigenicity. In Taiwan studies, betel quid chewing is the main cause of submucous fibrosis and oral cancer. Understanding the distribution and characteristics of the areca nut chewing population is one of the first steps in the effort to prevent these oral diseases. A stratified cluster random sample of 2442 junior high school students in Changhua county, Taiwan, were surveyed for the habit of areca nut chewing. Significantly more male students chewed areca nut than female students (9.2% vs 0.9%). The proportion of students who were chewing areca nuts increased with increasing (seventh to ninth) grades. Areca nut was used by junior high school students at a higher rate in village (rural) areas as compared to town (semi-urban) and city (urban) areas (6.4%, 3.7% and 3.0%, respectively). More students in the ordinary achievement classes were chewing areca nuts than those in the high achievement classes (8.4% vs 1.6%). Areca nut chewing students tended to have users in their families. Cigarette smoking and alcohol drinking were positively associated with areca nut chewing. More than half (53.6%) of the areca nut chewing students first experimented with this habit with a family member, most often the father or grandfather.

Risk of extrahepatic bileduct cancer after cholecystectomy.

The aetiology of cancer of the extrahepatic bile duct is unknown. Gallstones have been proposed to be a risk factor on the basis of ecological and epidemiological evidence. As gallstones are formed in the gallbladder, the occurrence of extrahepatic bileduct cancer in patients after cholecystectomy is of interest. All patients (62,734) who had had a cholecystectomy during 1965-1983 within the Uppsala Health Care Region, Sweden, were followed up to the end of 1987. Excluding the first year of follow-up, 23 cancers of the extrahepatic bileduct occurred vs 26.3 expected for a standardised incidence ratio (SIR) of 0.88 (95% confidence interval [CI] 0.56-1.31). 10 years or more after operation there was a greater reduction of risk (SIR = 0.27; 95% CI 0.06-0.80). Similar patterns were observed for men and women, and among patients who had undergone cholecystectomy only compared with those who had had their common bileducts explored. To assess surveillance bias the incidence of primary liver cancer was also analysed: SIR = 1.15; 95% CI 0.91-1.44 overall, and 10 years or more after cholecystectomy SIR = 0.98; 95% CI 0.66-1.40. This study shows a reduced risk of extrahepatic bileduct cancer 10 or more years after cholecystectomy, indicating that gallstones may be a cause of this cancer.

Breast-feeding and maternal smoking in the etiology of Crohn's disease and ulcerative colitis in childhood.

Medical records concerning pediatric or adolescent patients first diagnosed with Crohn's disease or ulcerative colitis in two New York hospitals during a 5-year period (1986 to 1990) were abstracted, and information concerning sex, age, race, birthplace, sibship size, birth order, maternal age at birth, month of birth, duration of breast-feeding, and maternal smoking was recorded. Medical records of patients presenting at the respective pediatric gastroenterology departments immediately before or after the patients with inflammatory bowel disease were seen were also abstracted in order to generate a control series. Data concerning 68 patients with Crohn's disease, 39 patients with ulcerative colitis, and 202 control patients were analyzed through multiple logistic regression. Breast-feeding was negatively associated with Crohn's disease (P approximately 0.04) and ulcerative colitis (P approximately 0.07), with relative risk point estimates around 0.5 and with evidence of duration-dependent trends in both instances. There was no evidence of association of either disease with maternal age at birth, birth order, maternal smoking, or season of birth.

Tobacco smoking and other factors in relation to serum alpha-1-antitrypsin.

Serum levels of alpha-1-antitrypsin were measured by radial immunodiffusion, and phenotypes were determined by electrofocusing in acrylamide gel in 160 subjects who were used as controls in a case-control study of hepatocellular carcinoma (HCC). The results were studied in relation to age, sex, diagnostic category, tobacco smoking, consumption of alcoholic beverages, presence of hepatitis B surface antigen (HBsAg), and serum levels of alphafetoprotein (AFP) by modeling the data through multiple regression. There was no relation of serum alpha-1-antitrypsin values with sex, HBsAg, AFP, consumption of alcoholic beverages, and diagnostic category (p > 0.25). By contrast, there were statistically significant dose-dependent positive associations of serum alpha-1-antitrypsin with age and tobacco smoking (p < 0.01 in both instances). The positive association of serum alpha-1-antitrypsin with tobacco smoking and the previously reported excessive elevation of serum alpha-1-antitrypsin in hepatitis B-negative tobacco-related cases of HCC suggest that alpha-1-antitrypsin is intimately related to the pathogenetic process linking tobacco smoking to HCC.

A case-control study of coronary heart disease in Athens, Greece.

A case-control study of coronary heart disease (CHD) was conducted in Athens, Greece. The case series consisted of 329 patients with electrocardiographically confirmed coronary infarct or a diagnostic coronary arteriogram, or both, who were admitted during a 16-month period to a major teaching hospital. Controls were 570 patients admitted to the same hospital just before or after the CHD cases for minor surgery; eye, ear, nose or minor urological problems; or chest problems definitely shown to be unrelated to CHD. All cases and controls were interviewed in the hospital wards and selected laboratory data were abstracted. The main analysis was done by modelling through multiple logistic regression, controlling for demographic variables as well as for the mutual confounding effects of the investigated risk factors. Obesity, hypertension, diabetes mellitus, elevated blood cholesterol and excessive coffee intake were significant (P < 0.02) independent risk factors with relative risk estimates in the 2- to 3-fold range. Non-significant positive associations were found with respect to tobacco smoking and modest coffee consumption, whereas non-significant negative associations were noted with respect to alcohol intake and regular exercise. A negative association with duration of afternoon siesta was of borderline statistical significance.

Twin membership and breast cancer risk.

Pregnancy estrogens are substantially elevated in twin pregnancies and are likely to be more so in the case of dizygotic twins. If levels of pregnancy estrogens were positively related to breast cancer risk in the offspring, female twin members would be expected to be at slightly higher risk. Data from an international case-control study were utilized to assess this hypothesis. The analysis was based on 870 cases with breast cancer and 2,641 hospital controls from two sites: Glamorgan, Wales (1965-1967), and Boston, Massachusetts (1965-1966). Seventeen cases were members of twin pairs, and 8 of them had a twin brother; 33 controls were members of twin pairs and 14 had a twin brother. Among all women, the odds ratios for breast cancer were as follows: for twins with brothers, 1.54 (95% confidence interval (CI) 0.64-3.71); for twins with sisters, 1.30 (95% CI 0.58-2.92); and for all twins, 1.40 (95% CI 0.77-2.55). The odds ratios were higher among premenopausal women. These findings are not conclusive, but they are compatible with the hypothesis that pregnancy estrogens may affect the risk of breast cancer in the offspring.

Age at first establishment of chronic hepatitis B virus infection and hepatocellular carcinoma risk. A birth order study.

It is frequently assumed that the risk of hepatocellular carcinoma related to hepatitis B virus is higher when chronic hepatitis B virus infection is acquired early in life. This hypothesis has never been directly evaluated. However, firstborn and secondborn children are exposed to common infections after their school enrollment, whereas laterborn children are exposed much earlier, through their older siblings. The authors analyzed sibship size and birth order data from a large case-control study of patients admitted to Athens, Greece, hospitals between April 1976 and October 1984. The analyses included 185 patients with hepatocellular carcinoma, 35 patients with metastatic liver cancer, and 432 other hospital controls. There was a tendency for cases of hepatocellular carcinoma to concentrate at higher birth orders. When the analysis was restricted to cases and controls who were positive for hepatitis B surface antigen, this tendency was even more notable. These results are compatible with the hypothesis that establishment of chronic hepatitis B virus infection at an early age increases the risk of hepatocellular carcinoma substantially more than does chronic infection with this virus established at a later age.

Evidence of prenatal influences on breast cancer risk.

Intrauterine exposure to high concentrations of endogenous pregnancy oestrogens may be important in the aetiology of breast cancer. In a nested case-control study we have assessed the relation between breast cancer risk and indicators of pregnancy oestrogen concentrations; pre-eclampsia/eclampsia is negatively related and measures of fetal size are positively related to oestrogen concentrations. Standard records for women born at Uppsala University Hospital between 1874 and 1954 were linked with records of invasive breast cancer cases, identified through their unique national registration numbers in the Swedish Cancer Registry during 1958-90. For each breast cancer case, we selected as potential controls female offspring of the first three mothers admitted to the hospital after the case's mother; only controls still living in Sweden and free from breast cancer when it was diagnosed in the case were finally included. Conditional logistic regression analysis was done for 458 breast cancer cases and 1197 matched controls. Pre-eclampsia/eclampsia was associated with a breast cancer rate ratio of 0.24 (95% confidence interval 0.09-0.70, p = 0.01). Linear trends for breast cancer incidence with increasing birth weight, birth length, and placental weight were positive but not significant. Thus, prenatal factors are important in breast carcinogenesis. Concentrations of pregnancy oestrogens may be one such factor, but other prenatal or perinatal factors cannot be excluded.

Strategies for blood screening for the hepatitis C virus and for the human immunodeficiency virus in high risk groups.

For many infectious agents, seroprevalence rate is low but has serious consequences and must therefore be kept out of donated blood supplies. However, screening to ensure the safety of blood supplies has an associated very high cost. For example, in blood banks, detection of all the harmful items in a large number of samples is an expensive and tedious process. The laboratory and statistical approaches to obtain significant savings by the pooling method were discussed from 1943, recently, there have been further discussions of pooling sera as a means to determining the HIV seroprevalence rate in the general population or the weed out all HIV-positive individuals in blood screening. Here we describe a simple mathematical method to weed out all HIV, and HCV seropositive units. The method is designed to maximize possible savings. Two examples illustrate the application of this method in determining the number to be pooled in each stage, and the resulting savings. When the prevalence rate is lower than 2 percent. our method offers savings of over 80 percent.

Beyond simple pooling for HIV screening.

We discuss some theoretical features underlying the successful uses of pooling in testing HIV seroprevalence. In particular it is shown that there is a scaling relation for the distribution of positive sera among the pools. A multi-stage pooling method consisting of repeatedly halving the positive pools is proposed. Concentrating on the number of tests required for screening all positive individuals the method is shown to be highly efficient in low prevalence situations.