Biomedical subjects

R E Tarone

Publications and source records attributed to R E Tarone.

At least 37 records · Page 2Linked to original sources

PubMed2000

Chromosome analysis of workers occupationally exposed to radiation at the Sellafield nuclear facility.

PURPOSE: To investigate the relationship between stable chromosome aberration frequency in peripheral blood lymphocytes and occupational cumulative radiation exposure. MATERIALS AND METHODS: Cytogenetic analysis using G-banding was performed on peripheral blood lymphocyte cultures from 104 workers from the British Nuclear Fuels PLC facility at Sellafield, UK. The study group comprised 61 men with lifetime cumulative doses > 500 mSv, 39 men with minimal exposure (i.e. < 50 mSv) who formed a control group and 4 men with intermediate doses. RESULTS: The slope of the dose-response, adjusted for smoking status, for translocations and insertions was 0.55+/-0.31 x 10(-2)/cell/Sv. Consideration of chromosome breakpoints for all aberrations combined in the radiation workers revealed an excess in the C group chromosomes and a deficit in the F group chromosomes with breakpoints being concentrated in the terminal regions whereas the distribution in the control group did not deviate from expectation. CONCLUSIONS: The dose-response was not significantly different from the parallel FISH analysis (Tucker et al. 1997) and confirms that chronic radiation exposure appears to be substantially less effective at inducing stable chromosome aberrations in comparison with acute exposure.

Adult↗

PubMed2000

A new xeroderma pigmentosum group C poly(AT) insertion/deletion polymorphism.

We found a common biallelic polymorphism (PAT) in the xeroderma pigmentosum complementation group C (XPC) DNA repair gene consisting of an insertion of 83 bases of A and T [poly(AT)] and a 5 base deletion within intron 9. We developed a PCR assay to resolve the XPC PAT+ and PAT- alleles and found that the PAT+ allele frequency was 0.44 in 156 cancer-free donors from the Johns Hopkins School of Public Health, 0.41 in 263 cancer-free donors from the Baltimore Longitudinal Study of Aging and 0.36 in samples from 216 unselected donors from NIH. We also found a single nucleotide polymorphism in exon 15 of the XPC gene (A2920C, Lys939-->Gln) that creates a new enzyme restriction site. This XPC exon 15 single nucleotide polymorphism occurred at a frequency of 0.38 in 98 NIH donors and is in linkage disequilibrium with the PAT locus. We developed an allele-specific complementation assay utilizing post-UV host cell reactivation to assess DNA repair capacity of polymorphic alleles. We found similar DNA repair with XPC 2920A and XPC 2920C. These common polymorphisms in the XPC DNA repair gene may be useful for molecular epidemiological studies of cancer susceptibility.

Adolescent↗

PubMed2000

Implications of stage-specific survival rates in assessing recent declines in prostate cancer mortality rates.

It has been noted that the most important evidence for a benefit of early detection of prostate cancer using prostate-specific antigen (PSA) testing would be a decline in prostate cancer mortality rates to levels below those existing before diagnostic use of PSA testing. We document a decrease in U.S. prostate cancer mortality rates in white men less than 85 years of age to levels below those existing in 1986, the year use of PSA testing was approved. In fact, for men 60-79 years of age, prostate cancer mortality rates were lower in 1997 than in any year since 1950. Although it has been argued that the decrease in prostate cancer mortality rates began too soon to be explained by PSA testing, stage-specific survival rates indicate that a rapid decrease in mortality may be explained by the large number of high-grade prostate cancers detected before metastasis. If recent decreases in U.S. prostate cancer mortality rates are due to early detection using PSA testing, randomized clinical trials investigating PSA testing will show early evidence of a mortality benefit.

Age Distribution↗

PubMed2000

Do confounding or selection factors of residential wiring codes and magnetic fields distort findings of electromagnetic fields studies?

In contrast with several previous studies, our recent large case-control study found little association between childhood acute lymphoblastic leukemia (ALL) and electric-power-line wire codes. Here we examine internal evidence from our study to assess the possibility that selection bias and/or confounding may have affected the findings. We compared the relation between childhood ALL and wire codes and direct measurements of magnetic fields in subjects who participated in all phases of the study with the relation in all subjects, including those who declined to allow access inside the home. We found that the odds ratio for ALL among those living in homes with very high current configurations increased by 23% when 107 "partial participants" were excluded. We found similar, but slightly smaller, increases in the odds ratios when we performed the same comparisons using direct measurements of magnetic fields, excluding subjects who allowed only a measurement outside the front door. "Partial participants" tended to be characterized by lower socioeconomic status than subjects who participated fully, suggesting possible selection bias. We also examined the relation between a large number of potential confounding variables and both proxy and direct measurements of magnetic fields. Univariate adjustment for individual variables changed the odds ratio for ALL by less than 8%, while simultaneous adjustment for several factors reduced the estimate by a maximum of 15%. We conclude that while confounding alone is unlikely to be an important source of bias in our own and previous studies of magnetic fields, selection bias may be more of a concern, particularly in light of the generally low response rates among controls in case-control studies.

Case-Control Studies↗

PubMed2000

Blood levels of organochlorines before and after chemotherapy among non-Hodgkin's lymphoma patients.

Several small studies suggest a link between environmental exposure to organochlorine compounds and risk of non Hodgkin's lymphoma (NHL). Because NHL is uncommon, studies of the topic often use a population-based case-control design, in which cases generally are enrolled after treatment has begun. If chemotherapy affects blood levels of organochlorines, exposure will be misclassified and findings distorted. To determine whether chemotherapy alters serum levels of organochlorines in NHL cases, we compared serum samples before and after treatment in 22 cases diagnosed with NHL between March 1994 and August 1995 and enrolled in a clinical trial at the United States National Cancer Institute's Clinical Center. The time difference between pretreatment and posttreatment samples ranged from 15 to 27 months with an average of 20 months. Laboratory analyses were conducted in blinded pretreatment and posttreatment pairs of the subjects. Pretreatment and posttreatment organochlorine serum levels were compared using Pearson correlation coefficient (r) and paired t test. The pretreatment and posttreatment serum levels were highly correlated for 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and polychlorinated biphenyls (PCBs) PCB-138, PCB-153, PCB-156, and total PCBs (ranging from 0.78 to 0.93). Serum levels of all of these organochlorines significantly decreased between initiation and completion of chemotherapy, 25% for total PCB (P = 0.0044), 28% for DDE (P = 0.0014), 25% for PCB-138 (P = 0.0053), 27% for PCB-153 (P = 0.0031), and 29% for PCB-156 (P = 0.045). Neither weight change nor lipid change was correlated with changes in chemical levels. There was no association between the length of time between blood draws and changes in chemical levels. Our data raise the possibility that lymphoma treatment depresses serum organochlorine levels.

Adult↗

PubMed2000

Nonparametric evaluation of birth cohort trends in disease rates.

BACKGROUND: Although interpretation of age-period-cohort analyses is complicated by the non-identifiability of maximum likelihood estimates, changes in the slope of the birth-cohort effect curve are identifiable and have potential aetiologic significance. METHODS: A nonparametric test for a change in the slope of the birth-cohort trend has been developed. The test is a generalisation of the sign test and is based on permutational distributions. A method for identifying interactions between age and calendar-period effects is also presented. RESULTS: The nonparametric method is shown to be powerful in detecting changes in the slope of the birth-cohort trend, although its power can be reduced considerably by calendar-period patterns of risk. The method identifies a previously unidentified decrease in the birth-cohort risk of lung-cancer mortality from 1912 to 1919, which appears to reflect a reduction in the initiation of smoking by young men at the beginning of the Great Depression (1930s). The method also detects an interaction between age and calendar period in leukemia mortality rates, reflecting the better response of children to chemotherapy. CONCLUSION: The proposed nonparametric method provides a data analytic approach, which is a useful adjunct to log-linear Poisson analysis of age-period-cohort models, either in the initial model building stage, or in the final interpretation stage.

Adult↗

PubMed2000

Age-period-cohort analyses of breast-, ovarian-, endometrial- and cervical-cancer mortality rates for Caucasian women in the USA.

BACKGROUND: Age-period-cohort analyses of US breast-cancer mortality rates reveal an unexpected decrease in risk for women born after 1948. Hormones are thought to play an important role in the aetiology of breast cancer and female gynaecologic cancers, and thus the evaluation of birth-cohort trends for female gynaecologic cancers may shed light on the declining breast-cancer risk among 'baby-boomers'. METHODS: Age-period-cohort analyses are applied to US mortality rates for breast cancer, ovarian cancer, endometrial cancer and cervical cancer from 1950 through 1995. RESULTS: Age-period-cohort analyses provide no clues regarding the declining birth-cohort risk for breast cancer in 'baby-boomers'. The birth-cohort curves for ovarian and endometrial cancers are roughly similar, and largely explained by known risk factors. The calendar-period curve for endometrial cancer reveals increased risk between 1960 and 1980, probably due to increased use of oestrogen replacement therapy. Changes in the birth-cohort curve for cervical cancer reflect, for the most part, changes in sexual activity. An unexpected significant increase in the calendar-period curve for ovarian cancer occurred around 1980. CONCLUSION: Most of the major changes in the calendar-period and birth-cohort curves for breast cancer and female gynaecologic cancers can be explained by documented changes in known risk factors and in medical practice. The decreasing breast-cancer birth-cohort risk among 'baby-boomers' and the increasing ovarian-cancer calendar-period curve after 1980 are recent changes that require further investigation.

Adult↗

PubMed1999

A method for identifying abrupt changes in U.S. cancer mortality trends.

BACKGROUND: Summaries of trends in cancer rates evaluated over a fixed, short period are informative, but methods that evaluate trends over a longer time period, identifying when changes occur as well as the magnitude of the changes, can provide additional information. METHODS: Cancer mortality trends from 1973-1995 were determined for more than 15 anatomic sites for white and black males and females using weighted piecewise linear regression analysis with a stepwise selection procedure. The dependent variable was the natural logarithm of the annual mortality rate, and the weight was the annual number of cancer deaths. The variability of estimated change points was examined by bootstrapping the residuals from the resulting models. RESULTS: For black males, cancer mortality rates declined in the 1990s due to decreases in lung, esophageal, oral cavity, and prostate cancer rates. However, there was no significant decline for cancer of the colon and rectum. For white males, cancer mortality rates declined in the 1990s due to declines in cancer of the lung and colon/rectum since the mid-1980s and declines in prostate cancer in the 1990s. For black females and white females, total cancer mortality rates declined, but not significantly. Cancer rates for all sites except the lung declined significantly in the 1990s for white, but not black, females due to declining trends for carcinoma of the colon and rectum since the mid-1980s and for breast cancer in the 1990s. CONCLUSIONS: A method for identifying major changes in cancer trends has been developed. Trends for cancer of the breast and colon/rectum indicate that gaps between rates for blacks and whites are widening.

Black People↗

PubMed1999

Cancer surveillance series: recent trends in childhood cancer incidence and mortality in the United States.

BACKGROUND: Public concern about possible increases in childhood cancer incidence in the United States led us to examine recent incidence and mortality patterns. METHODS: Cancers diagnosed in 14540 children under age 15 years from 1975 through 1995 and reported to nine population-based registries in the National Cancer Institute's Surveillance, Epidemiology, and End Results Program were investigated. Age-adjusted incidence was analyzed according to anatomic site and histologic categories of the International Classification of Childhood Cancer. Age-adjusted U.S. mortality rates were calculated. Trends in rates were evaluated by use of standard regression methods. RESULTS: A modest rise in the incidence of leukemia, the most common childhood cancer, was largely due to an abrupt increase from 1983 to 1984; rates have decreased slightly since 1989. For brain and other central nervous system (CNS) cancers, incidence rose modestly, although statistically significantly (two-sided P = .020), largely from 1983 through 1986. A few rare childhood cancers demonstrated upward trends (e.g., the 40% of skin cancers designated as dermatofibrosarcomas, adrenal neuroblastomas, and retinoblastomas, the latter two in infants only). In contrast, incidence decreased modestly but statistically significantly for Hodgkin's disease (two-sided P = .037). Mortality rates declined steadily for all major childhood cancer categories, although less rapidly for brain/CNS cancers. CONCLUSIONS: There was no substantial change in incidence for the major pediatric cancers, and rates have remained relatively stable since the mid-1980s. The modest increases that were observed for brain/CNS cancers, leukemia, and infant neuroblastoma were confined to the mid-1980s. The patterns suggest that the increases likely reflected diagnostic improvements or reporting changes. Dramatic declines in childhood cancer mortality represent treatment-related improvements in survival.

Adolescent↗

PubMed1999

Incorporation of zidovudine into leukocyte DNA from HIV-1-positive adults and pregnant women, and cord blood from infants exposed in utero.

OBJECTIVE: The nucleoside analog 3'-azido-3'-deoxythymidine (ZDV) has widespread clinical use but also is carcinogenic in newborn mice exposed to the drug in utero and becomes incorporated into newborn mouse DNA. This pilot study was designed to determine ZDV incorporation into human blood cell DNA from adults and newborn infants. DESIGN: In this prospective cohort study, peripheral blood mononuclear cells (PBMC) were obtained from 28 non-pregnant adults and 12 pregnant women given ZDV therapy, six non-pregnant adults with no exposure to ZDV, and six non-pregnant adults who last received ZDV > or = 6 months previously. In addition, cord blood leukocytes were obtained from 22 infants of HIV-1-positive, ZDV-exposed women and from 12 infants unexposed to ZDV. There were 11 mother-infant pairs involving HIV-1 -positive women. METHODS: DNA was extracted from PBMC obtained from non-pregnant HIV-1-positive adults taking ZDV, pregnant HIV-1-positive women given ZDV during pregnancy, and from adults not taking ZDV. Cord blood leukocytes were examined from infants exposed to ZDV in utero and from unexposed controls. DNA samples were assayed for ZDV incorporation by anti-ZDV radioimmunoassay (RIA). RESULTS: The majority (76%) of samples from ZDV-exposed individuals, pregnant women (8 of 12), non-pregnant adults (24 of 28), or infants at delivery (15 of 22), had detectable ZDV-DNA levels. The range of positive values for ZDV-treated adults and infants was 25-544 and 22-452 molecules ZDV/10(6) nucleotides, respectively. Analysis of 11 mother-infant pairs showed variable ZDV-DNA incorporation in both, with no correlation by pair or by duration of drug treatment during pregnancy. Two of the 24 samples from individuals designated as controls were positive by anti-ZDV RIA. The 20-fold range for ZDV-DNA values in both adults and infants suggested large interindividual differences in ZDV phosphorylation. CONCLUSIONS: Incorporation of ZDV into DNA was detected in most of the samples from ZDV-exposed adults and infants. Therefore, the biologic significance of ZDV-DNA damage and potential subsequent events, such as mutagenicity, should be

Adult↗

PubMed1999

Evolutionary conservation and somatic mutation hotspot maps of p53: correlation with p53 protein structural and functional features.

Missense mutations in p53 frequently occur at 'hotspot' amino acids which are highly conserved and represent regions of structural or functional importance. Using the p53 mutation database and the p53 DNA sequences for 11 species, we more precisely defined the relationships among conservation, mutation frequency and protein structure. We aligned the p53 sequences codon-by-codon and determined the degree of substitution among them. As a whole, p53 is evolving at an average rate for a mammalian protein-coding gene. As expected, the DNA binding domain is evolving more slowly than the carboxy and amino termini. A detailed map of evolutionary conservation shows that within the DNA binding domain there are repeating peaks and valleys of higher and lower evolutionary constraint. Mutation hotspots were identified by comparing the observed distribution of mutations to the pattern expected from a random multinomial distribution. Seventy-three hotspots were identified; these 19% of codons account for 88% of all reported p53 mutations. Both high evolutionary constraint and mutation hotspots are noted at amino acids close to the protein-DNA interface and at others more distant from DNA, often buried within the core of the folded protein but sometimes on its surface. The results indicate that targeting highly conserved regions for mutational and functional analysis may be efficient strategies for the study of cancer-related genes.

Chromosome Mapping↗

PubMed1999

Seroreactivity to human papillomavirus types 16, 18, 31, and 45 virus-like particles in a case-control study of cervical squamous intraepithelial lesions.

Serum IgG antibodies to human papillomavirus (HPV) types 16, 18, 31, and 45 virus-like particles were measured in a nested case-control study of cervical squamous intraepithelial lesions. HPV-16 seroreactivity was strongly associated with HPV-16 DNA detection (odds ratio, 9.0; 95% confidence interval, 4.4-19.4), and similar type specificity was observed for HPV-31 and -45. In contrast, seroreactivity to any type was associated with elevated seroreactivity to all others. Among cases and controls, HPV-16 showed the highest seroprevalence, with 23.8% of 80 cases and 10.5% of 258 controls seroreactive to HPV-16 alone, and another 27.5% and 5.4%, respectively, seroreactive to HPV-16 plus other types. Overall, 24 (30.0%) cases and 17 (6.6%) controls were seroreactive to multiple types. These data suggest that seroreactivity to a given type reflects mainly type-specific HPV infection as measured by DNA detection and may also signal past exposure to other types that are now only serologically detected.

Antibodies, Viral↗

PubMed1999

Residential exposure to magnetic fields: an empirical examination of alternative measurement strategies.

OBJECTIVES: To investigate the impact of measuring a single home then imputing information from another home among subjects who lived in two homes in a subset of the National Cancer Institute/Children's Cancer Group (NCI/CCG) investigation of residential exposure to magnetic fields and risk of childhood leukaemia. METHODS: Each subject's summary time weighted average (TWA) exposure was derived from measurements of two homes, weighted by the fraction of the reference period lived in the residence. The three cost efficient field work strategies examined were measuring: (a) the longer lived in home; (b) the currently lived in home; and (c) the former lived in home. Two different methods were used for imputing the missing values: (a) control mean imputation, (b) status specific mean imputation. The subject's summary exposure to magnetic fields estimated with each approach was compared with the subject's TWA calculated from measurements in both homes. The association between estimated exposure to magnetic fields and the risk of leukaemia under different approaches was examined with unconditional logistic regression analysis. RESULTS: The Pearson correlation coefficient between the two measurements within subjects was 0.31 (p < 10(-4), indicating a lack of independence of measurements. Differences were found between mean exposures in current and former homes of cases, and between longer and shorter lived in homes of controls. All methods with measurements from one of the homes in conjunction with imputation of measurements for the second home led to marked attenuation of risk estimates at the highest exposure category, particularly when measurements from current homes were used and those from former homes were imputed. CONCLUSION: Results argue against attempting to estimate lifetime magnetic field exposure from imputed values derived from current residences to fill in gaps caused by unmeasured residences previously lived in.

Bias↗

PubMed1998

Altered spectra of hypermutation in antibodies from mice deficient for the DNA mismatch repair protein PMS2.

Mutations are introduced into rearranged Ig variable genes at a frequency of 10(-2) mutations per base pair by an unknown mechanism. Assuming that DNA repair pathways generate or remove mutations, the frequency and pattern of mutation will be different in variable genes from mice defective in repair. Therefore, hypermutation was studied in mice deficient for either the DNA nucleotide excision repair gene Xpa or the mismatch repair gene Pms2. High levels of mutation were found in variable genes from XPA-deficient and PMS2-deficient mice, indicating that neither nucleotide excision repair nor mismatch repair pathways generate hypermutation. However, variable genes from PMS2-deficient mice had significantly more adjacent base substitutions than genes from wild-type or XPA-deficient mice. By using a biochemical assay, we confirmed that tandem mispairs were repaired by wild-type cells but not by Pms2(-/-) human or murine cells. The data indicate that tandem substitutions are produced by the hypermutation mechanism and then processed by a PMS2-dependent pathway.

Adenosine Triphosphatases↗

PubMed1998

Increased hypermutation at G and C nucleotides in immunoglobulin variable genes from mice deficient in the MSH2 mismatch repair protein.

Rearranged immunoglobulin variable genes are extensively mutated after stimulation of B lymphocytes by antigen. Mutations are likely generated by an error-prone DNA polymerase, and the mismatch repair pathway may process the mispairs. To examine the role of the MSH2 mismatch repair protein in hypermutation, Msh2-/- mice were immunized with oxazolone, and B cells were analyzed for mutation in their VkappaOx1 light chain genes. The frequency of mutation in the repair-deficient mice was similar to that in Msh2+/+ mice, showing that MSH2-dependent mismatch repair does not cause hypermutation. However, there was a striking bias for mutations to occur at germline G and C nucleotides. The results suggest that the hypermutation pathway frequently mutates G.C pairs, and a MSH2-dependent pathway preferentially corrects mismatches at G and C.

Animals↗

PubMed1998

Case-control study of childhood acute lymphoblastic leukemia and residential radon exposure.

BACKGROUND: Several ecologic analyses have shown significant positive associations between mean indoor radon concentrations and risk of leukemia at all ages (acute myeloid leukemia and chronic lymphocytic leukemia) and for children (all leukemia, acute myeloid leukemia, and acute lymphoblastic leukemia [ALL]). As part of an age-matched, case-control study of childhood ALL in the United States, we investigated the association between the incidence of ALL in children under age 15 years and indoor radon exposure. METHODS: Radon detectors were placed in current and previous homes of subjects where they resided for 6 months or longer. Children were included in analyses if radon measurements covered 70% or more of the 5-year period prior to diagnosis for case subjects (or from birth for case subjects under age 5 years) and the corresponding reference dates for control subjects. Radon levels could be estimated for 97% of the exposure period for the eligible 505 case subjects and 443 control subjects. RESULTS: Mean radon concentration was lower for case subjects (65.4 becquerels per cubic meter [Bqm(-3)]) than for control subjects (79.1 Bqm(-3)). For categories less than 37, 37-73, 74-147, and 148 or more Bqm(-3) of radon exposure, relative risks based on matched case-control pairs were 1.00, 1.22, 0.82, and 1.02, respectively, and were similar to results from an unmatched analysis. There was no association between ALL and radon exposure within subgroups defined by categories of age, income, birth order, birth weight, sex, type of residence, magnetic field exposure, parental age at the subject's birth, parental occupation, or parental smoking habits. CONCLUSIONS: In contrast to prior ecologic studies, the results from this analytic study provide no evidence for an association between indoor radon exposure and childhood ALL.

Carcinogens, Environmental↗

PubMed1998

Residential wire codes: reproducibility and relation with measured magnetic fields.

OBJECTIVES: To investigate the reproducibility of wire codes to characterise residential power line configurations and to determine the extent to which wire codes provide a proxy measure of residential magnetic field strength in a case-control study of childhood leukaemia conducted in nine states within the United States. METHODS: Misclassification of wire codes was assessed with independent measurements by two technicians for 187 residences. The association between categories of wire code and measured level of magnetic field was evaluated in 858 residences with both a wire code measurement and a 24 hour measurement of the magnetic field in the bedroom. The strength of the association between category of wire code and risk of leukaemia was examined in two regions with different average levels of magnetic field in homes with high categories of wire code. RESULTS: The reproducibility of any of three different classifications of wire codes was excellent (kappa > or = 0.89). Mean and median magnetic fields, and the percentage of homes with high magnetic fields increased with increasing category for each of the wire code classification schemes. The size of the odds ratios for risk of leukaemia and high categories of wire code did not reflect the mean levels of the magnetic field in those categories in two study regions. CONCLUSION: Misclassification of categories of wire code is not a major source of bias in the study. Wire codes provide a proxy measure of exposure to residential magnetic fields. If magnetic fields were a risk factor for leukaemia, however, there would be some attenuation of risk estimates based on wire codes because of misclassification of exposure to magnetic fields at both extremes of the wire code range. The lack of an association between high categories of wire code and risk of leukaemia cannot be explained by a failure of the wire code classification schemes to estimate exposure to magnetic fields in the study area.

Bias↗

PubMed1998

Association between childhood acute lymphoblastic leukemia and use of electrical appliances during pregnancy and childhood.

As part of a comprehensive study of residential magnetic field exposure in nine midwestern and mid-Atlantic states, we evaluated the use of appliances by 640 patients with acute lymphoblastic leukemia, 0-14 years of age, diagnosed between 1989 and 1993, and 640 matched control children. Mothers were interviewed regarding use of electrical appliances during their pregnancy with the subject and the child's postnatal use. The risk of acute lymphoblastic leukemia was elevated in children whose mothers reported use of an electric blanket or mattress pad during pregnancy [odds ratio (OR) = 1.59; 95% confidence interval (CI) = 1.11-2.29] but was reduced for use of sewing machines during pregnancy (OR = 0.76; 95% CI = 0.59-0.98). The risk of acute lymphoblastic leukemia was increased with children's use of electric blankets or mattress pads (OR = 2.75; 95% CI = 1.52-4.98) and three other electrical appliances (hair dryers, video machines in arcades, and video games connected to a television), but the patterns of risk for duration in years of use and frequency of use were inconsistent for most appliances used by children. Risks rose with increasing number of hours per day children spent watching television, but risks were similar regardless of the usual distance from the television. The inconsistency in the dose-response patterns for many appliances, reporting and selection bias, and the lack of an effect for measured 60 Hertz magnetic fields or wire codes in our companion study must be considered before ascribing these associations to exposures from magnetic fields.

Case-Control Studies↗