PubMed Health⌕ Search

Biomedical subjects

Laurence Freedman

Publications and source records attributed to Laurence Freedman.

11 recordsLinked to original sources
PubMed2006

Reduced repair of the oxidative 8-oxoguanine DNA damage and risk of head and neck cancer.

An increasing number of studies indicate that reduced DNA-repair capacity is associated with increased cancer risk. Using a functional assay for the removal of the oxidative DNA lesion 8-oxoguanine by the DNA-repair enzyme 8-oxoguanine DNA glycosylase 1 (OGG1), we have previously shown that reduced OGG activity is a risk factor in lung cancer. Here, we report that OGG activity in peripheral blood mononuclear cells from 37 cases with squamous cell carcinoma of the head and neck (SCCHN) was significantly lower than in 93 control subjects, frequency matched for age and gender. Retesting of OGG activity 3 to 4 years after diagnosis and successful treatment of 18 individuals who recovered from the disease showed that OGG activity values were similar to those determined at diagnosis, suggesting that reduced OGG activity in case patients was not caused by the disease. Logistic regression analysis indicated that the adjusted odds ratio (OR) associated with a unit decrease in OGG activity was statistically significantly increased [OR, 2.3; 95% confidence interval (95% CI), 1.5-3.4]. Individuals in the lowest tertile of OGG activity exhibited an increased risk of SCCHN with an OR of 7.0 (95% CI, 2.0-24.5). The combination of smoking and low OGG was associated with a highly increased estimated relative risk for SCCHN. These results suggest that low OGG is associated with the risk of SCCHN, and if confirmed by additional epidemiologic studies, screening of smokers for low OGG activity might be used as a strategy for the prevention of lung cancer and SCCHN.

Adult↗
PubMed2005

Should fetal weight growth curves be population specific?

BACKGROUND AND OBJECTIVES: The use of ultrasound to estimate fetal weight has become very common. Several studies have examined which fetal parameters predict best fetal weight, and based on those parameters fetal growth curves have been established. It is possible however, that fetal growth patterns differ across population groups, and therefore should be population specific. To establish fetal weight growth curve for the Israeli population and to compare it to the one currently used, suggested by Hadlock et al. METHODS: A cross-sectional study of singleton pregnancies was conducted. For each fetus the estimated weight was calculated using sonographic measurements of bi-parietal diameter, femur length, abdominal circumference, and head circumference. A regression analysis was used to evaluate the relationship between weight and fetal age. RESULTS: A growth curve was established based on measurements of 857 fetuses. There was a gradual increase in fetal weight from 99 grams at 14 weeks to 3505 grams at 40 weeks. There was a slight difference between the new curve and the one currently used. Comparing 3rd percentile curve of the one in use with ours, we found that the first curve fell outside our 95% confidence limits for weeks 14 to 23 (when it was too low) and for weeks 27 to 35 (when it was too high). Comparing the 97th percentile curves, we found that the current curve fell outside our 95% confidence limits for weeks 14 to 22 (when it was too low), and for weeks 25 to 37 (when it was too high). CONCLUSIONS: We recommend that the physicians in Israel use the new Israeli fetal weight curve. This curve may be useful, especially in situations where fetal weight is close to or below the 3rd percentile of Hadlock's curve in weeks 27-35, and when fetal weight is close to or above the 97th percentile of Hadlock's curve in weeks 14-22.

Anthropometry↗
PubMed2005

Modification of the computational procedure in Parker and Bregman's method of calculating sample size from matched case-control studies with a dichotomous exposure.

Several authors have addressed the problem of calculating sample size for a matched case-control study with a dichotomous exposure. The approach of Parker and Bregman (1986, Biometrics42, 919-926) is, in our view, one of the most satisfactory, since it requires specification of quantities that are often easily available to the investigator. However, its recommended implementation involves a computational approximation. We show here that the approximation performs poorly in extreme situations and can be easily replaced with a more exact calculation.

Case-Control Studies↗
PubMed2005

Long-term follow-up for brain tumor development after childhood exposure to ionizing radiation for tinea capitis.

Ionizing radiation is an established risk factor for brain tumors, yet quantitative information on the long-term risk of different types of brain tumors is sparse. Our aims were to assess the risk of radiation-induced malignant brain tumors and benign meningiomas after childhood exposure and to investigate the role of potential modifiers of that risk. The study population included 10,834 individuals who were treated for tinea capitis with X rays in the 1950s and two matched nonirradiated groups, comprising population and sibling comparison groups. The mean estimated radiation dose to the brain was 1.5 Gy. Survival analysis using Poisson regression was performed to estimate the excess relative and absolute risks (ERR, EAR) for brain tumors. After a median follow-up of 40 years, an ERR/Gy of 4.63 and 1.98 (95% CI = 2.43-9.12 and 0.73-4.69) and an EAR/Gy per 10(4) PY of 0.48 and 0.31 (95% CI = 0.28-0.73 and 0.12-0.53) were observed for benign meningiomas and malignant brain tumors, respectively. The risk of both types of tumors was positively associated with dose. The estimated ERR/Gy for malignant brain tumors decreased with increasing age at irradiation from 3.56 to 0.47 (P = 0.037), while no trend with age was seen for benign meningiomas. The ERR for both types of tumor remains elevated at 30-plus years after exposure.

Adolescent↗
PubMed2004

Nutrition and physical activity and chronic disease prevention: research strategies and recommendations.

A shortage of credible information exists on practical dietary and physical activity patterns that have potential to reverse the national obesity epidemic and reduce the risk of major cancers and other chronic diseases. Securing such information is a challenging task, and there is considerable diversity of opinion concerning related research designs and priorities. Here, we put forward some perspectives on useful methodology and infrastructure developments for progress in this important area, and we list high-priority research topics in the areas of 1) assessment of nutrient intake and energy expenditure; 2) development of intermediate outcome biomarkers; 3) enhancement of cohort and cross-cultural studies; and 4) criteria for and development of full-scale nutrition and physical activity intervention trials.

Biomarkers↗
PubMed2004

Germ-line ATM gene alterations are associated with susceptibility to sporadic T-cell acute lymphoblastic leukemia in children.

A major feature of ataxia-telangiectasia (A-T) is an increased risk of cancer, particularly of lymphoid malignancies. We studied ATM gene involvement in leukemic cells derived from 39 pediatric T-cell acute lymphoblastic leukemias (ALLs). Two types of sequence changes--truncating and missense--were identified in 8 T-cell ALL samples: 3 truncating changes, all previously identified in A-T (R35X, -30del215, 2284delCT), and 3 missense variants (V410A, F582L, F1463C) were found, none associated with loss of heterozygosity (LOH). In all patients studied, the mutation was present in the germ-line. A-T carriers, defined by the finding of truncating mutations, were found to be 12.9 times more frequent than in the normal population (P = 0.004). A normally ethnically matched population was screened for the 3 missense variants, and their frequency was significantly more prevalent (4.9-fold excess) than in the normal population (P = 0.03). Our data suggest there is some evidence of an association between missense alterations in the ATM gene and T-cell ALL. A significant difference in the mean age at diagnosis of T-cell ALL was noted between patients harboring an ATM sequence change and those with no change, 5.4 years and 9.7 years, respectively (P = 0.001). No ATM alterations were identified in relapse samples, indicating that ATM does not play a role in disease progression. The high prevalence of germ-line truncating and missense ATM gene alterations among children with sporadic T-cell ALL suggests an association with susceptibility to T-cell acute leukemia and supports the model of predisposition to cancer in A-T heterozygotes.

Ataxia Telangiectasia↗
PubMed2003

The analysis of the influence of birth order and other factors in multiple birth data.

We compare three methods which can be used to analyse the influence of birth order and other factors on health outcomes in multiple birth data. We consider marginal models based on generalized estimating equations (GEE) and two kinds of conditional models; conditional logistic regression (CLR) and mixed effects models (MEM). Although the models may be written similarly, there are differences in both the interpretation and the numerical values assigned to the parameters. Our main conclusion is that GEE and MEM are preferable to CLR since they provide more flexibility in dealing with missing values and covariates. The choice between GEE and MEM is less obvious and depends on the data, the parameter of interest and statistical power.

Birth Order↗
PubMed2003

Maximum likelihood estimator and likelihood ratio test in complex models: an application to B lymphocyte development.

In this paper we introduce a simple framework which provides a basis for estimating parameters and testing statistical hypotheses in complex models. The only assumption that is made in the model describing the process under study, is that the deviations of the observations from the model have a multivariate normal distribution. The application of the statistical techniques presented in this paper may have considerable utility in the analysis of a wide variety of complex biological and epidemiological models. To our knowledge, the model and methods described here have not previously been published in the area of theoretical immunology.

Animals↗
PubMed2002

Bias in dietary-report instruments and its implications for nutritional epidemiology.

OBJECTIVE: To evaluate measurement error structure in dietary assessment instruments and to investigate its implications for nutritional studies, using urinary nitrogen excretion as a reference biomarker for protein intake. DESIGN: The dietary assessment methods included different food-frequency questionnaires (FFQs) and such conventional dietary-report reference instruments as a series of 24-hour recalls, 4-day weighed food records or 7-day diaries. SETTING: Six original pilot validation studies within the European Prospective Investigation of Cancer (EPIC), and two validation studies conducted by the British Medical Research Council (MRC) within the Norfolk cohort that later joined as a collaborative component cohort of EPIC. SUBJECTS: A sample of approximately 100 to 200 women and men, aged 35-74 years, from each of eight validation studies. RESULTS: In assessing protein intake, all conventional dietary-report reference methods violated the critical requirements for a valid reference instrument for evaluating, and adjusting for, dietary measurement error in an FFQ. They displayed systematic bias that depended partly on true intake and partly was person-specific, correlated with person-specific bias in the FFQ. Using the dietary-report methods as reference instruments produced substantial overestimation (up to 230%) of the FFQ correlation with true usual intake and serious underestimation (up to 240%) of the degree of attenuation of FFQ-based log relative risks. CONCLUSION: The impact of measurement error in dietary assessment instruments on the design, analysis and interpretation of nutritional studies may be much greater than has been previously estimated, at least regarding protein intake.

Adult↗