Biomedical subjects

Loki Natarajan

Publications and source records attributed to Loki Natarajan.

26 records · Page 2Linked to original sources

PubMed2004

On the importance of using multiple methods of dietary assessment.

BACKGROUND: Plasma carotenoid concentrations reflect intake of vegetables and fruits, the major food sources of these compounds. This study compared the ability of 2 measures of dietary intake (24-hour diet recalls and food frequency questionnaires [FFQs]) to corroborate plasma carotenoid concentrations in a subset of women participating in a diet intervention trial. METHODS: Plasma carotenoid concentrations and dietary intakes, estimated from 24-hour diet recalls and FFQs, were examined at baseline and 1 year later in a subset of 395 study participants (197 intervention and 198 comparison group). We used longitudinal models to examine associations between estimated intakes and plasma carotenoid concentrations. These analyses were stratified by study group and adjusted for body mass index (BMI), plasma cholesterol concentration, and total energy intake. We conducted simulations to compare mean-squared errors of prediction of each assessment method. RESULTS: In mixed-effects models, the estimated carotenoid intakes from both dietary assessment methods were strongly associated with plasma concentrations of alpha-carotene, beta-carotene, and lutein. Furthermore, modeling the 2 sources of intake information as joint predictors reduced the prediction error. CONCLUSION: These findings underscore the importance of using multiple measures of dietary assessment in studies examining diet-disease associations.

Adult↗

PubMed2004

Erosion of regression effect in a survival study.

Lack of persistence, or erosion, of the regression effect is an alternative to proportional hazards of particular interest in many medical applications. Such a departure from proportional hazards is often the most likely direction in which the model may be inadequate. Questions such as, is the effect of treatment only transitory or to what extent does an initially measured prognostic variable maintain its impact, frequently arise. In the context of a simple changepoint model, we propose a test of the null hypothesis of proportional hazards against the specific alternative of erosion of the regression effect. The particular changepoint model used can be viewed as a first approximation to a more complex reality, an approximation that enables us to avoid specifically modeling the functional form that any erosion might take. Practical guidelines for carrying out the test are provided. The approach is illustrated in the context of a study on risk factors for breast cancer survival.

Biometry↗

PubMed2003

Interval estimates of the probability of toxicity at the maximum tolerated dose for small samples.

Following on from the work of O'Quigley et al., we investigate the performance of interval estimates of the probability of toxicity following completion of a phase I clinical trial. Our particular focus is on very small sample sizes, not uncommon in phase I studies. Specifically, we study the situations for which the sample sizes are 12 or 16. Simulations are used to show that the coverage of the confidence intervals, even for very modest sample sizes, are close to nominal in most cases. Averaged over the range of situations considered, coverage rates are accurate for both sample sizes of 12 and 16. As for the larger sample size of 20, studied previously, it is possible to obtain further, albeit modest, improvements via the use of the Cornish-Fisher inversion.

Antineoplastic Agents↗

PubMed2003

Identification of frame-shift intermediate mutant cells.

Frame-shift mutations at microsatellites occur as a time-dependent function of polymerase errors followed by failure of postreplicational mismatch repair. A cell-culture system was developed that allows identification of intermediate mutant cells that carry the mutation on a single DNA strand after the initial DNA polymerase errors. A plasmid was constructed that contained 13 repeats of a poly(dC-dA).poly(dG-dT) oligonucleotide immediately after the translation initiation codon of the enhanced GFP (EGFP) gene, shifting the EGFP gene out of its proper reading frame. The plasmid was introduced into human mismatch repair-deficient (HCT116, hMLH1-mutated) and mismatch repair-proficient (HCT116+chr3, hMLH1 wild type) colorectal cancer cells. After frame-shift mutations occurred that restored the EGFP reading frame, EGFP-expressing cells were detected, and two distinct fluorescent populations, M1 (dim cells) and M2 (bright cells), were identified. M1 cell numbers were stable, whereas M2 cells accumulated over time. In HCT116, single M2 cells gave rise to fluorescent colonies that carried a 2-bp deletion at the (CA)(13) microsatellite. Twenty-eight percent of single M1 cells, however, gave rise to colonies with a mixed fluorescence pattern that carried both (CA)(13) and (CA)(12) microsatellites. It is likely that M1 cells represent intermediate mutants that carry (CA)(13).(GT)(12) heteroduplexes. Although the mutation rate in HCT116 cell clones (6.2 x 10(-4)) was 30 times higher than in HCT116+chr3 (1.9 x 10(-5)), the proportion of M1 cells in culture did not significantly differ between HCT116 (5.87 x 10(-3)) and HCT116+chr3 (4.13 x 10(-3)), indicating that the generation of intermediate mutants is not affected by mismatch-repair proficiency.

Base Sequence↗

PubMed2003

Non-acute (residual) neurocognitive effects of cannabis use: a meta-analytic study.

The possible medicinal use of cannabinoids for chronic diseases emphasizes the need to understand the long-term effects of these compounds on the central nervous system. We provide a quantitative synthesis of empirical research pertaining to the non-acute (residual) effects of cannabis on the neurocognitive performance of adult human subjects. Out of 1,014 studies retrieved using a thorough search strategy, only 11 studies met essential a priori inclusion criteria, providing data for a total of 623 cannabis users and 409 non- or minimal users. Neuropsychological results were grouped into 8 ability domains, and effect sizes were calculated by domain for each study individually, and combined for the full set of studies. Using slightly liberalized criteria, an additional four studies were included in a second analysis, bringing the total number of subjects to 1,188 (i.e., 704 cannabis users and 484 non-users). With the exception of both the learning and forgetting domains, effect size confidence intervals for the remaining 6 domains included zero, suggesting a lack of effect. Few studies on the non-acute neurocognitive effects of cannabis meet current research standards; nevertheless, our results indicate that there might be decrements in the ability to learn and remember new information in chronic users, whereas other cognitive abilities are unaffected. However, from a neurocognitive standpoint, the small magnitude of these effect sizes suggests that if cannabis compounds are found to have therapeutic value, they may have an acceptable margin of safety under the more limited conditions of exposure that would likely obtain in a medical setting.

Cannabis↗

PubMed2003

Estimation of spontaneous mutation rates.

Spontaneous or randomly occurring mutations play a key role in cancer progression. Estimation of the mutation rate of cancer cells can provide useful information about the disease. To ascertain these mutation rates, we need mathematical models that describe the distribution of mutant cells. In this investigation, we develop a discrete time stochastic model for a mutational birth process. We assume that mutations occur concurrently with mitosis so that when a nonmutant parent cell splits into two progeny, one of these daughter cells could carry a mutation. We propose an estimator for the mutation rate and investigate its statistical properties via theory and simulations. A salient feature of this estimator is the ease with which it can be computed. The methods developed herein are applied to a human colorectal cancer cell line and compared to existing continuous time models.

Biometry↗

PubMed2002

A randomized trial of the effect of a plant-based dietary pattern on additional breast cancer events and survival: the Women's Healthy Eating and Living (WHEL) Study.

The Women's Healthy Eating and Living (WHEL) Study is a multisite randomized controlled trial of the effectiveness of a high-vegetable, low-fat diet, aimed at markedly raising circulating carotenoid concentrations from food sources, in reducing additional breast cancer events and early death in women with early-stage invasive breast cancer (within 4 years of diagnosis). The study randomly assigned 3088 such women to an intensive diet intervention or to a comparison group between 1995 and 2000 and is expected to follow them through 2006. Two thirds of these women were under 55 years of age at randomization. This research study has a coordinating center and seven clinical sites. Randomization was stratified by age, stage of tumor and clinical site. A comprehensive intervention program that includes intensive telephone counseling, cooking classes and print materials helps shift the dietary pattern of women in the intervention. Through an innovative telephone counseling program, dietary counselors encourage women in the intervention group to meet the following daily behavioral targets: five vegetable servings, 16 ounces of vegetable juice, three fruit servings, 30 g of fiber and 15-20% energy from fat. Adherence assessments occur at baseline, 6, 12, 24 or 36, 48 and 72 months. These assessments can include dietary intake (repeated 24-hour dietary recalls and food frequency questionnaire), circulating carotenoid concentrations, physical measures and questionnaires about health symptoms, quality of life, personal habits and lifestyle patterns. Outcome assessments are completed by telephone interview every 6 months with medical record verification. We will assess evidence of effectiveness by the length of the breast cancer event-free interval, as well as by overall survival separately in all the women in the study as well as specifically in women under and over the age of 55 years.

Adult↗

PubMedDate not supplied

Age and ethnicity differences in short-term heart-rate variability.

OBJECTIVE: Hypertension is more frequent and more severe in older individuals and in African Americans. Differences in autonomic nervous system activity might contribute to these differences. Autonomic effects on the heart can be studied noninvasively through analysis of heart rate variability (HRV). We examined the effects of age and ethnicity on HRV. METHODS: We studied 135 subjects (57 African Americans and 78 Caucasian Americans), aged 23 to 54 years. Using their surface electrocardiogram (ECG) data, we calculated the HRV indices with spectral analyses. High frequency (HF) power was used to index parasympathetic activity, whereas the ratio of low to high frequency power (LF/HF) was used to index sympathovagal balance. RESULTS: Three HRV indices (HF, LF power, and LF/HF) were significantly related to age in Caucasian Americans but not in African Americans. The effect of age, ethnicity, and the age-by-ethnicity interaction on HF and LF power was significant, even after controlling for gender, body mass index, and blood pressure. CONCLUSIONS: Young African Americans manifested a pattern of HRV response similarly to older Caucasian Americans. These results suggest that young African American individuals might show signs of premature aging in their autonomic nervous system.

Adult↗