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Biomedical subjects

M T Ruffin

Publications and source records attributed to M T Ruffin.

At least 19 recordsLinked to original sources
PubMed2000

Recruiting subjects in cancer prevention and control studies.

Recruitment of subjects is a critical aspect of prevention trials that is often overlooked by investigators. As a consequence, accrual time is often extended, workloads may become heavy, and resource utilization is increased in an effort to complete projects. Recruitment of healthy subjects in cancer prevention and control studies presents unique issues that need to be considered. The barriers to recruitment include participant issues, physician variables, features of the study design, and characteristics of the health care system in the United States. The authors provide their experience in overcoming these difficulties.

Case-Control Studies↗
PubMed2000

Genetic taste markers and preferences for vegetables and fruit of female breast care patients.

OBJECTIVE: To explore links between genetic responsiveness to the bitter taste of 6-n-propylthiouracil (PROP) and self-reported preferences for vegetables and fruit of female breast care patients. METHODS: PROP tasting was defined by detection thresholds and by perceived bitterness and hedonic ratings for PROP solutions. Nontasters, medium tasters, and supertasters were identified by their PROP thresholds and by the ratio of perceived bitterness of PROP to the perceived saltiness of sodium chloride solutions. Subjects rated preferences for vegetables and fruit using 9-point category scales. SUBJECTS/SETTING: A clinical sample of 170 patients with newly diagnosed breast cancer and 156 cancer-free control subjects were recruited from the University of Michigan Breast Care Center. STATISTICAL ANALYSES: Principal components factor analysis, one-way analyses of variance, and Pearson correlations and chi 2 tests were used to analyze taste and food preference data. RESULTS: Genetic responsiveness to PROP was associated with lower acceptance of cruciferous and selected green and raw vegetables (P < .05). Women who reported disliking such foods were medium tasters or supertasters of PROP. Preference ratings for fruit were unrelated to PROP taster status. APPLICATIONS/CONCLUSIONS: Women who are PROP tasters may be less likely to comply with dietary strategies for cancer prevention that emphasize consumption of cruciferous vegetables and bitter salad greens. Alternatively, PROP-sensitive women may seek to reduce bitter taste by adding fat, sugar, or salt.

Breast Neoplasms↗
PubMed2000

Prevention of cervix cancer.

Cervix carcinoma is an important health problem world-wide, being the second most common cancer among women, ranking first in many developing countries. A number of important epidemiological risk factors have been identified as contributing to the development of CIN and invasive cervix carcinoma. Of key importance is infection with human papillomavirus (HPV), which is the primary risk factor. There are evolving primary and secondary preventive strategies that could further reduce the burden from cervical carcinoma. The possible primary preventive strategies include risk reduction, diet or dietary supplements, HPV vaccines, and other chemopreventive agents. The possible advances in secondary preventive strategies include new technologies for Pap smears, HPV typing triage, and other adjuvant screening procedures. The impact of these strategies will depend upon evidence to support their use along with the characteristics of the population and environment in which they are used.

Anticarcinogenic Agents↗
PubMed1999

The psychosexual impact of human papillomavirus cervical infections.

BACKGROUND: Occult human papillomavirus (HPV) infection, present in approximately 20% of women in the United States, is usually sexually transmitted, associated with substantial health risks, and unpredictable in its resolution. The potential for adverse psychosexual alterations due to HPV infection in women considered at low risk for bacterial sexually transmitted diseases is substantial, but data is lacking. METHODS: This cross-sectional study was conducted with sexually active women aged 18 to 60 years who had been enrolled at community-based offices in the University of Michigan Vaginitis Study. Women found to have occult HPV infection of the cervix were notified, received physician consultation, and were encouraged to have colposcopy performed to assess lesion status. Responses to a follow-up written questionnaire for differences in psychosexual functioning and attitudes following diagnosis were compared among these women and those without HPV infection. RESULTS: The women enrolled were primarily white and had a current sexual partner at the time of enrollment. They had few sexually transmitted infections and few risk factors, yet 20% had unsuspected HPV infection. Psychosexual characteristics at baseline and at follow-up, as well as perceived changes in these characteristics by the women, did not differ between women with HPV infection and those without. Stratification by potential confounders, including the presence of a vaginal infection at the time of study enrollment, household income level, ethnic background, age, marital status, and sexual history, did not alter these results. CONCLUSIONS: Women at low risk for sexually transmitted diseases, but who had a cervical HPV infection, were similar to those not infected in reported psychosexual characteristics and functioning. Adverse changes in these characteristics between the time of the diagnosis and subsequent follow-up were no more likely in those with the diagnosis than in those without.

Adolescent↗
PubMed1998

Cancer chemoprevention. A new way to treat cancer before it happens.

Cancer chemoprevention uses noncytotoxic drugs or nutrients to prevent, retard, or delay carcinogenesis. The future of cancer chemoprevention depends on understanding key cellular growth and proliferation-controlling events, developing markers of molecular carcinogenesis, surrogate endpoint biomarkers, and targeted chemopreventive approaches.

Anticarcinogenic Agents↗
PubMed1998

Clinical models of chemoprevention for colon cancer.

Colon cancer is a common malignancy in the westernized world and is incurable in its advanced stages. This article summarizes the currently available information on colorectal cancer chemoprevention. A brief outline of the incidence and etiologic factors is followed by a discussion of the evidence on which chemopreventive strategies for colon cancer are modeled. This includes a description of the development of surrogate endpoint biomarkers and experimental models to study colorectal cancer chemopreventives, a review of the promising colorectal cancer chemopreventives, and a discussion of the issues to be addressed in the design of future chemoprevention trials. The article concludes with an emphasis on the development and validation of biomarkers and selection of high-risk cohorts using genetic and epidemiologic tools as the main goals of future colon cancer chemoprevention trials before large-scale, risk-reduction trials are conducted.

Animals↗
PubMed1998

Clinical models of chemoprevention for cervical cancer.

Cervical carcinoma creates a worldwide, significant population burden that potentially could be reduced by new preventive strategies for cervical cancer such as chemoprevention. Given the vast array of clinical and molecular information available relating to cervical cancer and the precursor lesions along with a growing number of new molecular techniques, a model is needed to guide further investigation. Such a model would facilitate research design, guide hypothesis development and testing, and focus the use of molecular data collection and analysis. This article reviews the clinical and molecular data of cervical cancer and the precursor lesions in order to develop a model for chemoprevention research in cervical cancer.

Chemoprevention↗
PubMed1998

Bioavailability of beta-carotene is lower in raw than in processed carrots and spinach in women.

Populations at risk of vitamin A deficiency usually rely on dietary provitamin A carotenoids to meet vitamin A needs, yet bioavailability of these compounds is influenced by several factors as follows: location in the plant source, the presence of other influencing dietary components, and type and extent of processing. The purpose of this study was to examine the plasma beta-carotene response to raw vs. processed carrots and spinach. Subjects were eight healthy females aged 23-36 y who consumed approximately 9.3 mg beta-carotene daily from either raw or thermally processed and pureed vegetables in two 4-wk treatment periods in a crossover study. Plasma concentrations of total, all-trans-, and cis-beta-carotene and alpha-carotene were measured at base line and the end of each treatment period by using HPLC assays. Total and all-trans (but not cis) plasma beta-carotene concentrations were significantly greater than base-line concentrations in the processed feeding period (P < 0. 04) and tended to be greater in the raw feeding period (P = 0.08). Daily consumption of processed carrots and spinach over a 4-wk period produced an increase in plasma beta-carotene concentration that averaged three times that associated with consumption of the same amount of beta-carotene from these vegetables in the raw form (P = 0.09). Increased cis isomers provided in the processed vegetables did not result in significantly greater plasma cis-beta-carotene isomer concentrations. These results suggest that isomerization of beta-carotene by heat treatment does not negate the enhanced beta-carotene uptake associated with consuming commercially processed vegetables compared with raw vegetables.

Adult↗
PubMed1997

Suppression of human colorectal mucosal prostaglandins: determining the lowest effective aspirin dose.

BACKGROUND: A variety of studies have supported the finding that regular intake of aspirin (acetylsalicylic acid) or nonsteroidal anti-inflammatory agents can affect colorectal cancer carcinogenesis. These agents inhibit the synthesis of prostaglandins. High levels of prostaglandins are observed in colon cancer tissues. PURPOSE: Experiments were planned to determine the lowest dose of aspirin that can markedly suppress the levels of mucosal prostaglandins E2 and F(2alpha) in colorectal mucosa and to determine whether a relationship exists between these levels and plasma levels of both acetylsalicylic acid and its metabolite, salicylic acid. METHODS: Healthy men and women aged 18 years or older participated in the study. The participants took a single, daily dose of aspirin (40.5, 81, 162, 324, or 648 mg) or a placebo for 14 days. Colorectal biopsy specimens were taken at baseline, 24 hours after the first dose of aspirin, and 24-30 hours and 72-78 hours after the last, i.e., fourteenth, daily dose of aspirin. The biopsy specimens were assayed for prostaglandins E2 and F(2alpha) by use of a competitive enzyme immunoassay. Plasma concentrations of acetylsalicylic acid and salicylic acid were determined by use of high-performance liquid chromatography. All P values are two-sided. RESULTS: A total of 65 subjects (10 receiving placebo, groups of 10 each receiving 40.5, 81, 162, or 324 mg of aspirin, and a group of 15 receiving 648 mg of aspirin) completed the protocol. One subject reported unacceptable drug-induced toxic effects and did not complete the protocol; other subjects reported acceptable side effects. The lowest dose to significantly suppress colorectal mucosal prostaglandin E2 concentrations from baseline at 24 hours after the first dose (by 22.6%; P = .002) and at 24-30 hours after the last dose (by 14.2%; P = .021) was 162 mg. At 72-78 hours after the last dose, there was significant suppression for subjects receiving 81 mg (by 23.7%; P = .008). The lowest dose to significantly suppress colorectal mucosal prostaglandin F(2alpha) concentrations from baseline at 24 hours after the first dose (by 18.3%; P = .032) was 324 mg. The lowest dose causing a marked reduction in the level of prostaglandin F(2alpha) at 24-30 hours (by 15.1%; P = .003) and 72-78 hours (by 23.0%; P = .0002) after the last dose was 40.5 mg. No detectable amounts of acetylsalicylic acid or salicylic acid were present in the plasma at any of the biopsy time points. CONCLUSIONS: The lowest doses of aspirin taken daily for 14 days to significantly suppress concentrations of colorectal mucosal prostaglandins E2 and F(2alpha) were 81 and 40.5 mg, respectively. The suppression occurred without detectable amounts of aspirin or salicylic acid in the plasma at the time points studied. On the basis of these observations, we recommend a single, daily dose of 81 mg of aspirin in future studies of this drug as a chemopreventive agent for colorectal cancer.

Adult↗
PubMed1997

Colon cancer chemoprevention: clinical development of aspirin as a chemopreventive agent.

We have studied aspirin as a potential chemopreventive for colorectal cancer, completing Phase I studies on aspirin pharmacology and potential biomarker assays (prostaglandins, PGE2 and PGF2 alpha and cyclooxygenase modulation) in normal human subjects. These studies have determined the optimal dose of aspirin for future Phase IIa and IIb chemopreventive trials in high-risk cohorts of patients for colon cancer. Aspirin's effects on rectal prostaglandins are prolonged, detectable even after aspirin and its metabolite are removed from the plasma. Aspirin-mediated inhibition of prostaglandin production in the human rectal epithelium may be related to direct suppression of cyclooxygenase transcription and not to enzyme inactivation by acetylation. A systematic method to monitor adherence (self-report, telephone contact, pill count, and microelectronic monitoring) has been established for future trials. Strategies to improve recruitment of high-risk cohorts have been developed. Phase IIa non-randomized studies with aspirin at 81 mg in high-risk cohorts (resected Duke's A colon cancer, Duke's C colon cancer treated with adjuvant therapy and disease-free at 5 years, history of colon adenomas > 1 cm, two or more first-degree relatives with colon cancer, and familial adenomatous polyposis and hereditary non-polyposis colorectal cancer syndromes) are currently being conducted for surrogate end-point biomarker (prostaglandins, cyclooxygenase, cellular mucins, and proliferation) modulation.

Animals↗
PubMed1996

Adherence to single daily dose of aspirin in a chemoprevention trial. An evaluation of self-report and microelectronic monitoring.

A consecutive sample of 64 healthy adults (33 female and 31 male) were recruited at the University of Michigan Medical Center, Ann Arbor. Data were available for analysis on 57 subjects. The participants were asked to take a single daily dose of aspirin ranging from 0 to 640 mg. Adherence to the daily aspirin ingestion was measured by self-report and the Medication Event Monitoring System (MEMS, Aprex Corp, Fremont, Calif); adherence rate for the study population was 35%. The adherence rates for all dosing errors between self-report and Medication Event Monitoring System were significantly different (P = .002). There was no significant gender difference in adherence rates. Adherence to regular aspirin ingestion was poor in healthy, paid subjects despite explicit, written and verbal instructions. Patient self-report alone is not a reliable measure of adherence.

Adult↗
PubMed1996

Carotenoids, vitamin A, and estrogen receptor status in breast cancer.

Among patients with breast cancer, tumors that contain estrogen receptors (ER) are associated with improved survival and better response to hormone therapy than those not expressing these receptors. The purpose of these case comparison studies was to examine the relationship between carotenoids, vitamin A, and the tumor ER status in women at diagnosis of primary breast cancer. The focus of the first study was the relationship between dietary intake and ER status, and the focus of the second study was the relationship between ER status and the plasma carotenoid, retinol, and tocopherol concentrations. We evaluated tumor ER status and self-reported dietary intake in 142 women and plasma concentrations of carotenoids, retinol, and tocopherols in 149 women, at diagnosis of breast cancer, before any medical or surgical treatment. In the first study the overall odds of ER-positive status were increased in relation to number of mammograms in the past five years, number of breast-fed babies, dietary carotenoid intake, and more frequent intake of yellow and green vegetables. Overall odds of ER-positive status were decreased in relation to years of oral contraceptive use and preformed vitamin A intake. In the second study older women, women with higher plasma lutein concentration, and women not using beta-carotene supplements were more likely to be ER positive, when data were adjusted for body mass index and factors that may influence breast cancer risk or hormonal status. Significant independent relationships between plasma retinol or tocopherol concentrations and ER status were not observed. The strong and independent relationships between carotenoid intake, plasma lutein concentration, and ER status may relate to observations linking a carotenoid-rich diet with improved prognosis after diagnosis of breast cancer.

Adolescent↗
PubMed1995

Surrogate endpoint biomarkers for cervical cancer chemopreventive trials.

Cervical intraepithelial neoplasia (CIN) represents a spectrum of epithelial changes that provide an excellent model for developing chemopreventive interventions for cervical cancer. Possible drug effect surrogate endpoint biomarkers are dependent on the agent under investigation. Published and preliminary clinical reports suggest retinoids and carotenoids are effective chemopreventive agents for CIN. Determination of plasma and tissue pharmacology of these agents and their metabolites could serve as drug effect intermediate endpoints. In addition, retinoic acid receptors could serve a both drug and biological effect intermediate endpoints. Possible biological effect surrogate endpoint biomarkers include cytomorphological parameters, proliferation markers, genomic markers, regulatory markers, and differentiation. Given the demonstrated causality of human papillomavirus (HPV) for cervical cancer, establishing the relationship to HPV will be an essential component of any biological intermediate endpoint biomarker. The pathologic effect surrogate endpoint biomarker for cervical cancer is CIN, used clinically for years. The desired effect for chemopreventive trials is complete regression or prevention progression. In planning chemoprevention trials, investigators need to consider spontaneous regression rates, the subjective nature of detecting CIN, and the impact of biopsy on regression. If intermediate endpoint biomarkers that met the above criteria were available for cervical cancer, then new chemopreventive agents could be rapidly explored. The efficacy of these new agents could be determined with a moderate number of subjects exposed to minimal risk over an acceptable amount of time. The impacts on health care for women would be significant.

Anticarcinogenic Agents↗