Practicing safe modeling: GLP for biologically based mechanistic models.
Explore the source record for details and available documents.
Biometry↗
Biomedical subjects
C M Lyles
Publications and source records attributed to C M Lyles.
Childhood infections and the risk of inflammatory bowel disease.
Adults with inflammatory bowel disease from North Carolina were questioned during 1986 and 1987 to assess risk due to a variety of childhood infections and treatments with antibiotics. Responses were compared with those of neighbor controls. Persons with Crohn's disease were more likely to report an increased frequency of childhood infections in general (odds ratio 4.67, 95% CI 2.65-8.23) and pharyngitis specifically (odds ratio 2.14, 95% CI 1.30-3.51). This was validated by an increased frequency of tonsillectomy (odds ratio 1.53, 95% CI 1.07-2.20). Crohn's cases were more likely to report frequent treatment with antibiotics for both otitis (odds ratio 2.07, 95% CI 1.03-4.14) and pharyngitis (odds ratio 2.14, 95% CI 1.20-3.84). Although Crohn's cases were more likely to report frequent exposure to penicillin (odds ratio 1.81, 95% CI 0.98-3.31), there did not appear to be excess risk conferred by penicillin after controlling for frequency of infections. Persons with ulcerative colitis also reported an excess of infections generally (odds ratio 2.37, 95% CI 1.19-4.71), but not an excess of specific infections or treatments with antibiotics. Persons who reported an increased frequency of infections tended to have an earlier onset of Crohn's disease (P < 0.0001) and ulcerative colitis (P = 0.04). Finally, it was noted that urban living in childhood increased the risk for Crohn's disease. We conclude that childhood infections may be a risk factor for Crohn's disease and may presage the early onset of disease.
Adolescent↗
Diet and risk of colorectal adenomas: macronutrients, cholesterol, and fiber.
BACKGROUND: Diet is thought to be important in the etiology of colorectal cancer. Studies suggest that a diet high in red meat and saturated fat and low in dietary fiber and vegetables may increase cancer risk. Diet may also be important in the development of colorectal adenomas that are precursors of most colorectal cancers, but this hypothesis has not been well studied. PURPOSE: This case-control study was designed to examine the effects of dietary consumption of cholesterol, fiber (vegetables, fruits, beans, and grains), and macronutrients (protein, carbohydrate, and fat) on risk for colorectal adenomas. METHODS: Analyses were based on data from 236 subjects (105 men and 131 women) with histologically confirmed adenomas (cases) and 409 adenoma-free control subjects (165 men and 244 women), all of whom had had colonoscopy. Case and control subjects were similar with respect to gender, body mass, race, marital status, education, and indications for colonoscopy. Using a validated quantitative food-frequency questionnaire, an experienced graduate nutritionist interviewed each subject by telephone. Sex-specific analyses were conducted because the ranges of nutrient intake were substantially different for men and women. Odds ratios (ORs) were calculated according to quintiles of nutrient intake. RESULTS: Carbohydrate intake was inversely related to adenoma risk in women (P for trend = .002). Compared with women in the lowest quintile of carbohydrate consumption, those in the highest quintile were 60% less likely to develop adenomas (OR = 0.39; 95% confidence interval [CI] = 0.19-0.80). Intake of fruit (P for trend = .028) and intake of fiber derived from vegetables and fruits (P for trend = .012) were also inversely related to adenomas in women. Total fat showed a positive association in women (P for trend = .004), with an OR of 2.69 for the highest versus the lowest quintile (95% CI = 1.31-5.50). Results were comparable for saturated fat (P for trend = .027). The risks in men were generally similar in direction and magnitude but were not statistically significant. CONCLUSIONS: These data support the hypothesis that a diet high in fat and low in carbohydrates, fruits, and fruit and vegetable fiber increases risk not only for colorectal cancer but also for precursor colorectal adenomas. IMPLICATIONS: These results, which are consistent with findings of other investigators, suggest that environmental factors, influencing risk for colorectal cancer, such as a high-risk diet, may lead to development of the precursor adenomas.
Adenoma↗
Cigarette smoking, alcohol, and the risk of colorectal adenomas.
BACKGROUND: The present study was designed to further assess the reported association between cigarette smoking, alcohol, and colorectal adenomas. METHODS: A number of environmental and life-style risk factors were examined in 236 patients with histologically proven adenomas and 409 controls with no adenomas. RESULTS: Age, sex, race, and indication for procedure were similar in cases and controls. Those who had ever smoked were not at increased risk for adenomas compared with those who had never smoked. Years of smoking, cigarettes per day, and total pack-years showed no dose-response effect. Results for men and women were similar. Alcohol was a significant risk factor for men but not for women. Men in the highest quartile of daily caloric intake from alcohol were more than four times more likely than nondrinkers to develop adenomas, with a statistically significant trend in risk from the lowest to the highest quartile. These findings persisted after controlling for other potential risk factors for adenomas. The risk for colon and rectal polyps were similar. Men in the highest tertile of beer consumption were nearly six times more likely to develop adenomas than nondrinkers. CONCLUSIONS: Beer drinking is a risk factor for colorectal adenomas in this population.
Adenoma↗
Rectal mucosal ornithine decarboxylase activity is not a useful marker of risk for colorectal neoplasia.
Rectal mucosal ornithine decarboxylase activity has been reported to distinguish patients with adenomas from normal controls. In order to further explore this association, we assayed biopsy samples from 119 unselected individuals undergoing routine colonoscopic examinations. The overall mean ODC activity was 127.4 (+/- 93.1 SD) pmol/mg protein/hr. There were no differences by age, sex, or race. Tissue handling and storage influenced ODC activity. Specimens collected and transported on Dry Ice had higher ODC activity than specimens initially frozen in a -20 degrees C freezer. After adjusting for storage and collection method, the activity was similar in subjects with adenomas (126.3 pmol/mg/hr) compared to those without adenomas (128.8 pmol/mg/hr). We conclude that variations in assay technique make comparisons between laboratories difficult. Patients with large-bowel adenomas do not necessarily have higher ODC activity in uninvolved rectal mucosa. Further study of the environmental and genetic factors that influence rectal mucosal proliferation may improve our understanding of carcinogenesis in the large bowel.
Adenoma↗
Oral contraceptive use and the risk of inflammatory bowel disease.
We used rosters of the Crohn's and Colitis Foundation of America to identify potential cases and peer-nominated controls to explore the reported association between oral contraceptives and inflammatory bowel disease. Overall, women who used oral contraceptives were at increased risk of developing Crohn's disease (odds ratio = 1.49, 95% confidence interval (CI) = 0.99-2.26). The findings persisted after adjustment for age at symptom onset, decade of onset, education, marital status, and location of disease. There was an interaction with cigarette smoking; the risk associated with oral contraceptives was elevated in current smokers (odds ratio = 2.64, 95% CI = 1.22-5.75), but not in former smokers or never-smokers. The risk was not elevated for ulcerative colitis (odds ratio = 1.10, 95% CI = 0.65-1.85).
Adolescent↗
Reproducibility and variability of the rectal mucosal proliferation index using proliferating cell nuclear antigen immunohistochemistry.
Rectal mucosal proliferation has been shown to be increased in patients with neoplastic lesions of the large bowel and may serve as a marker of risk for colorectal malignancy. We conducted analyses to determine reliability and components of variability that might suggest optimal analysis strategies for studies of proliferation. Endoscopic pinch biopsies were obtained from 17 adult patients, labeled using proliferating cell nuclear antigen, scored using strict rules, and then rescored. Labeling index, defined as the proportion of labeled cells in a crypt, was calculated for each crypt, biopsy, subject, and group. There was excellent reproducibility. The technician was able to select previously scored crypts 95% of the time. The overall labeling index was identical on repeat. There was considerable variability in labeling index among crypts from a single biopsy and between biopsies of a single subject. Variance component estimates suggested that 20% of the variability of labeling index was due to subject, 30% due to the biopsy within a subject, and 50% due to crypts within a biopsy. There were substantial gains in statistical power by scoring two biopsies rather than one. There was less gain from further increases in biopsy number. There was little statistical advantage for counting more than 8 crypts/biopsy. Demonstrating a decrease of 25% in the mean labeling index with 90% power could require more than 100 subjects/group. We conclude that proliferating cell nuclear antigen is an extremely reproducible method to determine proliferation index. There is considerable variability among subjects, biopsies, and crypts.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Comparison of rectal mucosal proliferation measured by proliferating cell nuclear antigen (PCNA) immunohistochemistry and whole crypt dissection.
Rectal mucosal proliferation has been promoted as an intermediate marker for risk of colorectal neoplasia. Proliferating cell nuclear antigen (PCNA) immunohistochemistry has become a standard method to measure cell proliferation. Whole-crypt dissection may provide a technically simpler method for determining proliferation within an entire crypt. We conducted a study to assess the reliability (reproducibility) of whole-crypt dissection in 10 subjects. Reliability of whole-crypt dissection with the subject as the unit of observation was excellent. The intraclass correlation coefficient for subjects was 0.93. Biopsy-to-biopsy reliability was lower (r=0.86) and crypt-to-crypt reliability lower still (r = 0.35). There was poor correlation between measures of proliferation index using the two techniques (Kendall's tau = 0.13; P = 0.08). Compartment analysis based on the percentage of the total number of labeled cells appearing in each crypt quartile also did not demonstrate a significant correlation between the two measures. We conclude that PCNA labeling index and whole-crypt mitotic count are not comparable measures of rectal mucosal proliferation.
Biopsy↗