Biomedical subjects

J I Wurzelmann

Publications and source records attributed to J I Wurzelmann.

8 recordsLinked to original sources

PubMed1997

In vivo activation of mitogen-activated protein kinases in rat intestinal neoplasia.

BACKGROUND & AIMS: To investigate whether mitogen-activated protein kinase (MAPK) cascades might play a role in the progression of colon cancer, c-Jun N-terminal kinase (JNK) and extracellular signal regulating kinase (ERK) activity during colonic tumorigenesis were examined. METHODS: The 1,2-dimethylhydrazine (DMH)-induced colon carcinoma model was used to study the activation of these kinases during intestinal carcinogenesis. Male Sprague-Dawley rats were injected with DMH for 24 weeks. Normal-appearing intestinal mucosa from control and treated animals and DMH-induced intestinal tumors were assayed for JNK and ERK activity using solid phase in vitro kinase assays. Tumors were typed for mutations in the K-ras gene. RESULTS: There was little or no difference in JNK and ERK activity in hyperproliferative mucosa from DMH-treated animals compared with normal mucosa from control animals. However, in 16 colonic neoplasms, an average of 23-fold and 29-fold increases in JNK and ERK activities were observed, respectively, over control levels. In addition, activating protein-1 binding was strongly induced in the colonic tumors. Activation did not correlate with the presence of mutations in K-ras. CONCLUSIONS: Both the JNK and ERK MAPKs are highly activated during late progression of colorectal carcinoma. This change is dependent on the tumorigenic state rather than changes in proliferation.

1,2-Dimethylhydrazine↗

PubMed1997

Plasma selenium levels and the risk of colorectal adenomas.

Previous research has suggested that selenium may protect against the development of colorectal neoplasia. We examined the potential chemopreventive properties of selenium against colorectal adenomas while controlling for a number of dietary and life-style factors. We conducted a cross-sectional study among patients referred for colonoscopy to University of North Carolina Hospitals. Cases had one or more pathologically confirmed adenomas, and noncases had none. Plasma selenium levels were determined using graphite furnace atomic absorption spectrometry with Zeeman background correction and platform technique. Odds ratios were calculated using logistic regression analysis adjusting for potential confounders. The mean plasma selenium concentrations for cases (n = 37) and noncases (n = 36) were 107 and 120 micrograms/l, respectively (p = 0.06). Those in the fourth quartile of plasma selenium level had 0.24 times the risk (95% confidence interval = 0.06-1.04) for colorectal adenomas of those in the first quartile. The adjusted odds ratio for colorectal adenomas was 0.58 (95% confidence interval = 0.31-1.08) for a 30 microgram/l increase in plasma selenium level. Lower plasma selenium levels were associated with multiple adenomas but not with adenoma size or location. These data support a protective effect of selenium against colorectal adenomas after adjustment for possible confounders. Selenium might be a potentially useful chemopreventive agent for colorectal neoplasia.

Adenoma↗

PubMed1996

Iron intake and the risk of colorectal cancer.

Prospectively gathered data from the National Health and Nutrition Examination Survey I and the National Health Evaluation Follow-Up Study were analyzed to evaluate the risk of colorectal cancer due to consumption of iron. Morbidity and mortality data due to colorectal cancer were available on 14,407 persons first interviewed in 1971 and followed through 1986. A total of 194 possible colorectal cancers occurred in this group over the 15-year period. Subsite analysis showed that the risk of colon cancer due to iron intake was elevated throughout the colon for both men and women, with the highest adjusted risks for the interquartile range seen in the proximal colon for females (relative risk, 1.51; 95% confidence interval, 1.41-1.60). The risk of rectal cancer was not significantly elevated for men or women. Elevated serum iron was also associated with increased risk; however, this effect was strongest in the distal (rather than proximal) colon and was significant only among females (adjusted relative risk, 1.73; 95% confidence interval, 1.03-2.92). The mean transferrin saturation was higher among cases than controls (30.7 versus 28.7%), but total iron-binding capacity did not seem to predict the occurrence of colorectal cancer. Proportional hazards models confirmed that the effects of iron and serum iron were not confounded by age, gender, energy consumption, fat intake, or other known risk factors for colorectal cancer. These data suggest that iron may confer an increased risk for colorectal cancer, and that the localization of risk may be attributable to the mode of epithelial exposure. It seems that luminal exposure to iron increases risk proximally, whereas humoral exposure increases risk distally. These differences may be due to such factors as oxidation state, binding proteins and the presence of other cofactors such as bile acids, products of bacterial metabolism.

Adult↗

PubMed1995

Rational approach to small polyps found on sigmoidoscopy.

Most colorectal cancers are thought to develop from benign adenomas. Because adenomas are found in a large proportion of asymptomatic individuals, most adenomas must remain benign. Current guidelines suggest that colonoscopy is not necessary when hyperplastic polyps are found at screening sigmoidoscopy. Existing data suggest that small adenomatous polyps may also not be associated with substantial risk of current or future malignancy. We suggest that small polyps seen on flexible sigmoidoscopy require neither biopsy nor subsequent colonoscopy. Such an approach requires further study, but could result in substantial cost savings, with modest risk to patients.

Adenomatous Polyps↗

PubMed1995

Evaluating risk: a primer for gastroenterologists.

OBJECTIVE: To review the various types of risk measures and to illustrate how interpretations may vary depending on how risk is presented. METHODS: We define different types of risk estimates and provide examples of their use from the recent gastroenterological literature. RESULTS: Calculations of absolute risk and the number of patients who must receive treatment to prevent one patient from experiencing a disease state (number needed to treat) provide useful information in assessing the utility of fecal occult blood testing for prevention of colorectal cancer and in estimating small bowel cancer rates for individuals with familial adenomatous polyposis. CONCLUSIONS: Measures such as relative risk and the odds ratio are best used in analyzing causality but may not be helpful in guiding clinical decisions. Absolute risk and attributable risk reveal the actual number of cases that can be explained by a given exposure and can thereby measure the impact of a clinical intervention for both the population and the patient. These measures should be the criteria for decision-making.

Adenomatous Polyposis Coli↗

PubMed1994

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↗

PubMed1992

Childhood exposure to environmental tobacco smoke and the risk of ulcerative colitis.

Previous reports have suggested that there may be a protective effect of active cigarette smoking on the risk of ulcerative colitis. Because passive smoking may also have other health consequences, the authors examined the effect of exposure to environmental tobacco smoke during childhood on adult risk of ulcerative colitis in a case-control study of 172 cases drawn in 1986-1987 from the rosters of North Carolina chapters of the Crohn's & Colitis Foundation of America and 131 peer-nominated neighborhood controls. Active smokers were less likely to develop ulcerative colitis than were nonexposed nonsmokers (odds ratio = 0.53, 95% confidence interval 0.24-1.14). The risk was also decreased in passive smokers, i.e., those whose parents had smoked (odds ratio = 0.50, 95% confidence interval 0.25-1.00). Risk estimates were not related to sex, education, age at onset of symptoms, or year of onset of symptoms. Both active smoking in adulthood and passive childhood exposure to environmental tobacco smoke appear to decrease the risk of ulcerative colitis. The results indicate that childhood passive smoke exposures can influence adult susceptibility to ulcerative colitis.

Adult↗

PubMed1992

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↗