Effect of an integrated nutrition curriculum on medical education, student clinical performance, and student perception of medical-nutrition training.

BACKGROUND: Ninety-eight percent of medical schools report nutrition as a component of medical education. However, most schools do not have an identifiable nutrition curriculum. Medical schools that do include nutrition have not evaluated its effect on clinical skills. OBJECTIVE: The objective was to determine the efficacy of an integrated undergraduate medical curriculum to increase the quantity of nutrition instruction and to advance nutrition clinical skills demonstrated by medical students. DESIGN: A quasiexperimental design was constructed to determine whether an integrated nutrition curriculum increased the performance on nutrition-oriented clinical examinations of medical school classes that received 1, 2, or 3 y of the curriculum. The evaluation of the curriculum focused on 3 areas: 1) hours of nutrition instruction, 2) the application of nutrition within a clinical setting, and 3) perceptions about the nutrition curriculum. The Objective Structured Clinical Examination (OSCE) nutrition score was compared between graduating classes by use of analysis of variance. Data from the American Association of Medical Colleges were analyzed to determine the change in the proportion of students who reported that the amount of time devoted to nutrition was adequate. RESULTS: The implementation of the integrated nutrition curriculum resulted in a doubling of the total hours of required instruction in the medical curriculum (35 compared with 75 h). The mean (+/-1 SEM) OSCE nutrition score significantly improved after the implementation of the curriculum (41.7 +/- 0.9% compared with 50.6 +/- 1.1%) and the percentage of students who reported that the amount of nutrition taught during medical school was inadequate decreased (68.4% compared with 11.5%). CONCLUSION: Medical students improved their clinical nutrition practice skills through participation in an integrated nutrition curriculum.

Reduction in fat intake is not associated with weight loss in most women after breast cancer diagnosis: evidence from a randomized controlled trial.

BACKGROUND: A reduction in dietary fat intake has been suggested as a method to promote weight loss in women at risk for breast cancer recurrence. METHODS: Weight change in response to diet intervention was examined in 1010 women who had completed treatment for Stage I, Stage II, or Stage IIIA (American Joint Committee on Cancer staging system) primary operable breast cancer during their first year of participation in a randomized, controlled, diet intervention trial to reduce risk of recurrence. Diet intervention was performed by telephone counseling and promoted a low fat diet that also was high in fiber, vegetables, and fruit. The comparison group was provided with general dietary guidelines to reduce disease risk. Multiple linear regression models were used to examine the relations among demographic and personal characteristics, changes in diet composition and exercise level, and change in body weight or body mass index. RESULTS: The average weight change in the 1-year period was 0.04 kg for the intervention group and 0.46 kg for the comparison group. For the total group, body weight was stable (+/- 5% baseline weight) for 743 women (74%), whereas 114 (11%) lost weight, and 153 (15%) gained weight. These distributions were similar in the two study groups inclusive of all study participants and for only those women with a baseline body mass index of > or = 25 kg/m2. Initial body mass index and changes in fiber and vegetable intakes, but not change in percent of energy obtained from fat, were associated independently with change in weight or body mass index. CONCLUSIONS: For most women at risk for breast cancer recurrence, diet intervention to promote a reduction in fat intake was not associated with significant weight loss. Testing the effect of a substantial change in diet composition on risk for breast cancer recurrence is unlikely to be confounded by weight loss in subjects who were the recipients of intensive intervention efforts.

Diet and prevention of colorectal cancer.

There is a 20-fold difference in incidence rates of colorectal cancer between the areas of highest incidence (North America and Australia) and lowest incidence (India). Animal studies, epidemiologic research, and clinical trials continue to focus on diet in the search for responsible environmental factors. Between 1997 and 1999, a number of research areas have had considerable activity, and they provide the focus for this review. Among foods, vegetables, cereals, and soy have been topics of recent research. Nutrients from foods and supplements have also gained attention, including n-3 fatty acids, calcium, and B vitamins. Gene-environment interactions are beginning to be studied in populations. Studies of the interaction between polymorphisms in the gene for methylenetetrahydrofolate reductase (MTHFR) and dietary components for risk of both colorectal cancer and adenomatous polyps provide a glimpse into the future of diet and cancer research.

An integrated nutrition curriculum in medical education.

R25 grant support from the NIH/NCI enabled the University of Arizona to assess nutrition education, develop and evaluate specific course content, and move toward comprehensive prevention-based nutrition education in 1991-1997. Hours of nutrition education increased to 115% over baseline, and students indicated greater satisfaction with the amount of nutrition instruction they received. Especially valuable was a course in prenatal and infant nutrition that paired each student with a pregnant patient. After the grant support ended, nutrition began to be crowded out of the curriculum by other, more traditional, topics, but a 57% gain over baseline was sustained. External support for nutrition education is urgently needed.

Low-energy reporting in women at risk for breast cancer recurrence. Women's Healthy Eating and Living Group.

This study examined the extent of low-energy reporting and its relationship with demographic and lifestyle factors in women previously treated for breast cancer. This study used data from a large multisite clinical trial testing the efficacy of a dietary intervention to reduce risk for breast cancer recurrence (Women's Healthy Eating and Living Study). Using the Schofield equation to estimate energy needs and four 24-h dietary recalls to estimate energy intakes, we identified women who reported lower than expected energy intakes using criteria developed by G. R. Goldberg et al. (Eur. J. Clin. Nutr., 45: 569-581, 1991). We examined data from 1137 women diagnosed with stage I, stage II, or stage IIIA primary, operable breast cancer. Women were 18-70 years of age at diagnosis and were enrolled in the Women's Healthy Eating and Living Study between August 19, 1995, and April 1, 1998, within 4 years after diagnosis. The Goldberg criteria classified about one-quarter (25.6%) as low-energy reporters (LERs) and 10.8% as very LERs. Women who had a body mass index >30 were almost twice (odds ratio, 1.95) as likely to be LERs. Women with a history of weight gain or weight fluctuations were one and a half times as likely (odds ratio, 1.55) to be LERs as those who were weight stable or weight losers. Age, ethnicity, alcohol intake, supplement use, and exercise level were also related to LER. Characteristics (such as body mass index, age, ethnicity, and weight history) that are associated with low-energy reporting in this group of cancer survivors are similar to those observed in other populations and might affect observed diet and breast cancer associations in epidemiological studies.

Fat intake and risk of squamous cell carcinoma of the skin.

The varied effects of different classes of dietary fatty acids on carcinogenesis suggest that fatty acid composition is an important determining factor in tumor development. In the present study, we investigated the association between dietary n-3 and n-6 fatty acid intake and risk of squamous cell carcinoma of the skin (SCC). Data were taken from a population-based case-control study of skin SCC in Southeastern Arizona. Our data show a consistent tendency for a lower risk of SCC with higher intakes of n-3 fatty acids [p (for trend) = 0.055]. The adjusted odds ratios for increasing levels of n-3 fatty acids were 0.85 [95% confidence interval (CI) = 0.56-1.27] and 0.71 (95% CI = 0.49-1.00) compared with the lower level as the referent. For the ratio of n-3 to n-6 fatty acids, the odds ratios in successively higher levels were 0.88 (95% CI = 0.59-1.32) and 0.74 (95% CI = 0.51-1.05), suggesting a tendency toward decreased risk of SCC with increased intake of diets with high ratio of n-3 to n-6 fatty acid. More studies are clearly needed to elucidate the function of dietary fatty acids so that recommendations can be made to alter the human diet for cancer prevention, particularly in light of the increasing incidence of SCC of the skin.

Lack of effect of a high-fiber cereal supplement on the recurrence of colorectal adenomas. Phoenix Colon Cancer Prevention Physicians' Network.

BACKGROUND: The risks of colorectal cancer and adenoma, the precursor lesion, are believed to be influenced by dietary factors. Epidemiologic evidence that cereal fiber protects against colorectal cancer is equivocal. We conducted a randomized trial to determine whether dietary supplementation with wheat-bran fiber reduces the rate of recurrence of colorectal adenomas. METHODS: We randomly assigned 1429 men and women who were 40 to 80 years of age and who had had one or more histologically confirmed colorectal adenomas removed within three months before recruitment began to a supervised program of dietary supplementation with either high amounts (13.5 g per day) or low amounts (2 g per day) of wheat-bran fiber. The primary end point was the presence or absence of new adenomas at the time of follow-up colonoscopy. Subjects and physicians, including colonoscopists, were unaware of the group assignments. RESULTS: Of the 1303 subjects who completed the study, 719 had been randomly assigned to the high-fiber group and 584 to the low-fiber group. The median times from randomization to the last follow-up colonoscopy were 34 months in the high-fiber group and 36 months in the low-fiber group. By the time of the last follow-up colonoscopy, at least one adenoma had been identified in 338 subjects in the high-fiber group (47.0 percent) and in 299 subjects in the low-fiber group (51.2 percent). The multivariate adjusted odds ratio for recurrent adenoma in tile high-fiber group, as compared with the low-fiber group, was 0.88 (95 percent confidence interval, 0.70 to 1.11; P=0.28), and the relative risk of recurrence according to the number of adenomas, in the high-fiber group as compared with the low-fiber group, was 0.99 (95 percent confidence interval, 0.71 to 1.36; P=0.93). CONCLUSIONS: As used in this study, a dietary supplement of wheat-bran fiber does not protect against recurrent colorectal adenomas.

Citrus peel use is associated with reduced risk of squamous cell carcinoma of the skin.

Limonene has demonstrated efficacy in preclinical models of breast and colon cancers. The principal sources of d-limonene are the oils of orange, grapefruit, and lemon. The present case-control study was designed to determine the usual citrus consumption patterns of an older Southwestern population and to then evaluate how this citrus consumption varied with history of squamous cell carcinoma (SCC) of the skin. In this Arizona population, 64.3% and 74.5% of the respondents reported weekly consumption of citrus fruits and citrus juices, respectively. Orange juice (78.5%), orange (74.3%), and grapefruit (65.3%) were the predominant varieties of citrus consumed. Peel consumption was not uncommon, with 34.7% of all subjects reporting citrus peel use. We found no association between the overall consumption of citrus fruits [odds ratio (OR) = 0.99, 95% confidence interval (CI) = 0.73-1.32] or citrus juices (OR = 0.97, 95% CI = 0.71-1.31) and skin SCC. However, the most striking feature was the protection purported by citrus peel consumption (OR = 0.66, 95% CI = 0.45-0.95). Moreover, there was a dose-response relationship between higher citrus peel in the diet and degree of risk lowering. This is the first study to explore the relationship between citrus peel consumption and human cancers. Our results show that peel consumption, the major source of dietary d-limonene, is not uncommon and may have a potential protective effect in relation to skin SCC. Further studies with large sample sizes are needed to more completely evaluate the interrelationships between peel intake, bioavailability of d-limonene, and other lifestyle factors.

Reliability and validity of a self-administered food frequency questionnaire in a chemoprevention trial of adenoma recurrence.

Various chemoprevention trials have assessed dietary intake by means of food frequency questionnaires. However, it is important to assess the degree to which such questionnaires can measure diet. We conducted reproducibility and validity analyses of our Arizona Food Frequency Questionnaire (AFFQ) in our recently completed, randomized, Phase III chemoprevention trial testing the effects of a wheat bran fiber supplement on colorectal adenoma recurrence. A total of 139 individuals provided a baseline and year 1 AFFQ and a set of 4-day dietary records collected over a period of 1 month. The reproducibility analyses of the AFFQ administered 1 year apart showed a mean intraclass correlation of 0.54 for unadjusted nutrients and 0.48 for energy-adjusted nutrients. The relative validity of the AFFQ, as compared with the average of the 4-day diet records, showed a mean deattenuated correlation of 0.49 (range, 0.22-0.65) for the baseline AFFQ and 0.49 (range, 0.25-0.67) for the year 1 AFFQ. When data from both AFFQs were combined and compared with the diet records, there was a slight improvement in the overall deattenuated correlations (mean, 0.56; range, 0.33-0.71). The correlations we observed for macro- and micronutrient intake were within the overall range of those reported in the literature. Reliability and validity studies of dietary instruments are feasible in the setting of a chemoprevention trial and should be conducted when the instrument's performance has not been previously assessed in the target population.

Estrogen profiles in postmenopausal African-American women in a wheat bran fiber intervention study.

High dietary fiber intake has been hypothesized to lower blood estrogen concentrations, an effect thought to be beneficial for decreasing breast cancer risk. This study investigated the association between dietary supplementation of wheat bran and circulating estrogen levels in postmenopausal African-American women participating in a community intervention trial. Seventeen postmenopausal women (aged 63 +/- 1.6 yr) participated in the study. Nutritional status was assessed and blood and 24-hour urine samples were collected before and after five to six weeks of daily supplementation of the diet with 35 g of wheat bran cereal (11.6 g insoluble dietary fiber) marked with 28 mg of riboflavin. Riboflavin confirmed that all postmenopausal participants adhered to the intervention protocol. Nine of the 17 postmenopausal women were taking some form of estrogen replacement therapy (PM-ERT). Baseline hormone levels in the PM-ERT group did not significantly change after the dietary intervention. Estradiol (96.8 +/- 20.3 vs. 113.8 +/- 23.3 pg/ml), androstenedione (0.47 +/- 0.06 vs. 0.45 +/- 0.06 ng/ml), and sex hormone-binding globulin (SHBG, 107 +/- 13.5 vs. 106.6 +/- 13.3 nmol/l) levels remained constant. In the eight postmenopausal women who were not receiving exogenous hormones (PM), wheat bran consumption was not associated with predicted decreased levels of estradiol (25.7 +/- 2.7 vs. 31.0 +/- 1.9 pg/ml), estrone (38.3 +/- 10.1 vs. 39.3 +/- 10.6 pg/ml), and androstenedione (0.78 +/- 0.08 vs. 0.68 +/- 0.11 ng/ml) or with increased concentrations of SHBG (35.2 +/- 6.4 vs. 34.8 +/- 6.5 nmol/l). Participants receiving ERT had baseline and postintervention levels of estradiol and SHBG significantly higher and androstenedione significantly lower than those not receiving ERT. No association between wheat bran supplementation and hormone levels was found in PM or PM-ERT African-American participants. These results in postmenopausal women are in contrast to findings of earlier studies in premenopausal women indicating that wheat bran fiber decreases serum sex hormones. Estrogen levels in postmenopausal women are only 5-10% of those in premenopausal women; therefore, a high wheat bran fiber diet alone may not be sufficient to depress these low levels even further.

Design and baseline characteristics of study participants in the Wheat Bran Fiber trial.

The Wheat Bran Fiber (WBF) trial is a Phase III clinical trial designed to assess the effect of a WBF intervention for 3 years on the recurrence of adenomatous polyps. Men and women, 40-80 years of age, who had removal of one or more colorectal adenoma(s) 3 mm or larger within 3 months prior to study entry were recruited from three sites in the Phoenix metropolitan area. After meeting eligibility criteria, 1509 individuals entered a 6-week run-in period, consisting of a low WBF (2 g/day) intervention. Participants (n = 1429) successfully completed this phase and were randomized to a high (13.5 g/day) or low (2 g/day) WBF intervention. Various data and specimens were collected at baseline and throughout the intervention phase, which included dietary intake, physical activity, other risk factor information, blood specimens, rectal biopsies, and polyp tissues. The study design called for a colonoscopy at approximately 1 year after the qualifying colonoscopy; thus, the period between the first year and the final colonoscopy will be used to assess the effect of the intervention, which is expected to be completed in the latter part of 1998.

Development of a urinary riboflavin adherence marker for a wheat bran fiber community intervention trial.

Development of a reliable marker of adherence to high-fiber diets is essential for accurately assessing dietary fiber intake in community interventions and clinical trials. The objective of this study was to evaluate the feasibility of using a riboflavin tracer incorporated into wheat bran cereal to determine fiber intake and compare results to the more traditional methodology of measuring stool weight. The inpatient phase of the study established that the excretion of urinary riboflavin was highly correlated with the dose of the riboflavin-spiked wheat bran cereal (r = 0.95, P < 0.005) and could be used as a biomarker to validate fiber supplement intake. The outpatient clinical intervention included a group of seven African-American men and women, who were asked to incorporate 1/2 cup of wheat bran cereal (11.6 g of dietary fiber) into their daily diet for a 6-week period. The cereal was spiked with a 28-mg dose of riboflavin. Baseline measurements of urinary riboflavin and stool weight were compared to postintervention levels. Comparison of pre- and postintervention measures of riboflavin excretion showed a significant increase (0.8 +/- 0.1 versus 6.0 +/- 0.6 mg/day, P < 0.02), which confirmed a high level of adherence to the dietary intervention. Although wet stool weights at baseline were significantly lower than postintervention (106 +/- 20 versus 146 +/- 23 g/day; P < 0.03), differences in dry stool weights did not reach significant levels (28 +/- 4 versus 33 +/- 5 g/day, P < 0.30). Furthermore, pre- and poststool measurements overlapped and could not provide definitive data on participant adherence. These results indicate that the riboflavin tracer was a more sensitive biomarker of wheat bran fiber supplementation than stool weight and provided an accurate method for validating adherence to the dietary intervention. A riboflavin marker provides a valid technique for adherence assessment in large-scale community trials, in which collection of 3-day fecal samples is not a manageable option.

Use of a food frequency questionnaire to screen for dietary eligibility in a randomized cancer prevention phase III trial.

Cancer prevention clinical trials use food frequency questionnaires (FFQs) to assist in eligibility screening. FFQ reliability and validity studies are available, but these studies do not evaluate FFQs as screening tools. The Wheat Bran Fiber Trial of the University of Arizona used a FFQ as an eligibility screen with the goal of screening out subjects whose true daily calcium intake was less than 500 mg per day (for safety) and whose true dietary fiber intake was greater than 30 g per day (for safety and trial efficiency). Subjects ineligible by FFQ were interviewed for final dietary eligibility determinations. A study was undertaken within the Wheat Bran Fiber Trial to evaluate the sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of the FFQ used in this context. Four-day food records were collected on 183 potential participants before entry into the study. Using the 4-day averages as the "true" value, sensitivity, specificity, positive predictive value, and NPV were calculated for men and women separately under two screening conditions: using the target calcium and dietary fiber values and using "revised" values identified in interim analysis within the study. NPV was acceptable in all analyses. Sensitivity for low calcium intake was inadequate under the original criteria (0.33 for men and 0.09 for women) but acceptable under the revised criteria (0.80 for men and 0.81 for women). With the revised criteria, specificity declined, resulting in heavy screening burdens deemed worthwhile for the safety considerations. Dietary fiber eligibility screening worked well at target values. These differences were not predicted by reliability/validity studies.

The effect of wheat bran fiber and calcium supplementation on rectal mucosal proliferation rates in patients with resected adenomatous colorectal polyps.

Colorectal cancers continue as the second most common cause of death from cancer in the United States. Only a few prospective, randomized clinical trials have been performed to evaluate the potential preventive effects of dietary fiber or calcium in patients with an increased risk for the development or recurrence of colorectal cancer. We designed and conducted a double-blinded, placebo-controlled randomized trial involving supplementation of fiber and calcium intake and measurements of [3H]thymidine labeling index (LI) percentages in rectal mucosal biopsies obtained from patients with resected colorectal adenomas to examine the potential mechanisms by which dietary interventions might reduce colorectal cancer risk. We performed a randomized, double-blinded, Phase II study, using a factorial design to measure the effects of supplemental dietary wheat bran fiber (2.0 or 13.5 g/day) and calcium carbonate (250 or 1500 mg/day elemental calcium) supplementation on [3H]thymidine LI percentages in rectal mucosal crypts and 24-h in vitro outgrowth cultures. Measurements were made at baseline randomization (i.e., after a 3-month placebo run-in period using 2.0 g of wheat bran fiber plus 250 mg of calcium carbonate) and after 3 and 9 months on treatment in 100 randomized participants who had a history of colon adenoma resection. Neither the wheat bran fiber nor the calcium carbonate supplements significantly reduced [3H]thymidine LI percentages in rectal mucosal crypts (total or compartmental analysis) or 24-h in vitro outgrowth cultures at either 3 or 9 months of daily supplementation in the 93 evaluable participants. We conclude that 9 months of high-dose wheat bran fiber and calcium carbonate supplementation in study participants with a history of recently resected colorectal adenomas does not have a significant effect on cellular proliferation rates in rectal mucosal biopsies, comparing 3- and 9-month results to baseline results. Ultimately, there is great need for the evaluation of these two different nutrient interventions in the setting of Phase III studies wherein adenomatous polyp recurrence, rather than a rectal mucosal biomarker, serves as the primary end point.

Women's health initiative. Why now? What is it? What's new?

Studies collectively named the Women's Health Initiative (WHI) are currently enrolling 164,500 postmenopausal women in several overlapping clinical trials and an observational study. The overall goals of WHI are to understand the determinants of postmenopausal women's health and to evaluate the efficacy of practical interventions in preventing the major causes of morbidity and mortality in older women. This article reviews the research leading to the WHI studies; describes the study designs and protocols, with an emphasis on what's new about WHI from a psychological perspective; and outlines the major psychosocial hypotheses under investigation and the major challenges WHI presents to psychological science.

Smoking experimentation and initiation among adolescent girls: qualitative and quantitative findings.

OBJECTIVE: To use qualitative and quantitative findings to describe patterns of smoking experimentation and initiation among adolescent girls. DESIGN: Ethnographic in-person interviews, focus groups, telephone interviews, and a survey questionnaire were used over a one-year period. The paper reports on cross-sectional data drawn from a three-year longitudinal study. SUBJECTS AND SETTING: 205 girls participated in the survey and interviews during year 3 of the study. Girls were drawn from two urban high schools in Tucson, Arizona (USA), and were in grades 10 and 11 (mean ages 16 and 17, respectively) during year 3. RESULTS: Overall, 30% (n = 61) of informants reported that they currently smoked, 7% (n = 15) were ex-smokers, and 63% (n = 129) were "non-smokers". The most frequently cited reasons for smoking were stress reduction and relaxation. Several stress-inducing situations, including family environment, social relations with classmates, and schoolwork, are discussed. The notion of peer pressure is re-examined in the light of teenagers' experience that there is little overt pressure to initiate smoking. Consonant with notions of adolescent autonomy, the theme of independence in smoking initiation and continuation permeated girls' narratives about their smoking behaviour. Girls projected the image that they could control their cigarettes rather than have their cigarettes control them. CONCLUSIONS: Smoking prevention and cessation programmes need to address and counter the smoking/relaxation association, which was identified as an important reason for smoking among adolescent girls. Questions typically used in surveys to measure smoking behaviour do not adequately define the smoking experience as described by teenagers.

New carotenoid values for foods improve relationship of food frequency questionnaire intake estimates to plasma values.

Carotenoid consumption is of great interest in disease prevention studies. Until recently, carotenoid food composition data have not been available from a single laboratory source with high validity/reliability characteristics. With the availability of a new carotenoid food composition data base, we examined the impact of the new data base on the intake estimates as measured by a food frequency questionnaire and on the relationship of those estimates to plasma values to ascertain what, if any, improvement is achieved through use of the new values. Plasma samples were available for 162 healthy adults participating in cancer prevention studies at the Arizona Cancer Center, including men and women, smokers and nonsmokers. A single laboratory analyzed plasma samples for beta-carotene, alpha-carotene, lutein, and lycopene. All subjects had completed a modified version of the Block food frequency questionnaire, which calculates carotenoids using a literature-based algorithm. A new carotenoid composition data base using recently published data (A.R. Mangels et al., J. Am. Diet. Assoc., 93: 284-296, 1993) was then directly substituted for the Block data base. There were high correlations between intake estimates derived from the two data bases for all four carotenoids (range, r = 0.76-0.96). Average intake estimates based on the Mangels et al. data base were significantly higher for beta-carotene and lycopene; however, correlations between intakes and plasma values were significantly different only for beta-carotene (r = 0.44 for Mangels versus 0.32 for Block, P = 0.015).

Four Corners Research Consortium for Native Americans and cancer research.

Cancer morbidity and mortality in Native Americans in the Southwestern four-corners region of the United States (Arizona, Colorado, New Mexico, and Utah) is of critical concern to public health workers, health care providers, cancer researchers, and Native American communities of the region. As a follow-up to the national conference in Seattle, Washington, representatives from the Arizona, Colorado, New Mexico, and Utah Cancer Centers, the AMC Cancer Research Center, and the Indian Health Service participated in a regional conference on September 26, 1995. The primary reason for the "Four Corners Consortium" meeting was to assess cancer research activities in each state and to determine how Native American cancer research could be organized in the four-state region. One interest of the group was to determine strategies to explore why some cancers are more or less prevalent among Southwest Native American populations and to evaluate how the group might jointly establish research that would address the cancer needs of Southwestern tribes.

Analysis of multivariate reliability structures and the induced bias in linear model estimation.

Least squares provides consistent estimates of the regression coefficients beta in the model E[Y [symbol: see text] x] = beta x when fully accurate measurements of x are available. However, in biomedical studies one must frequently substitute unreliable measurements X in place of x. This induces bias in the least squares coefficient estimates. In the univariate case, the bias manifests itself as a shrinkage toward zero, but this result does not generalize. When x is multivariate, then there are no predictable relationships between the signs or magnitudes of actual and estimated regression coefficients. In this article, we characterize the estimation bias, and review a relatively simple adjustment procedure to correct it. We also show that several natural conjectures about the bias are false. We present three definitions of reliability coefficient matrices that generalize the univariate case, and we illustrate their application to dietary intake data from a cancer prevention study.