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Biomedical subjects

Mack T Ruffin

Publications and source records attributed to Mack T Ruffin.

14 recordsLinked to original sources

Human papillomavirus in amniotic fluid.

BACKGROUND: There is evidence to suggest that human papillomavirus (HPV) can cross the placenta resulting in in-utero transmission. The goal of this study was to determine if HPV can be detected in amniotic fluid from women with intact amniotic membranes. METHODS: Residual amniotic fluid and cultured cell pellets from amniocentesis performed for prenatal diagnosis were used. PGMY09/11 L1 consensus primers and GP5+/GP6+ primers were used in a nested polymerase chain reaction assay for HPV. RESULTS: There were 146 paired samples from 142 women representing 139 singleton pregnancies, 2 twin pregnancies, and 1 triplet pregnancy. The women were 78% Caucasian, 5% African American, 14% Asian, and 2% Hispanic. The average age was 35.2 years with a range of 23-55 years. All samples were beta-globin positive. HPV was not detected in any of the paired samples. CONCLUSION: Given the age range, race, and ethnicity of the study population, one would anticipate some evidence of HPV if it could easily cross the placenta, but there was none.

Journal Article↗

Dose escalation of a curcuminoid formulation.

BACKGROUND: Curcumin is the major yellow pigment extracted from turmeric, a commonly-used spice in India and Southeast Asia that has broad anticarcinogenic and cancer chemopreventive potential. However, few systematic studies of curcumin's pharmacology and toxicology in humans have been performed. METHODS: A dose escalation study was conducted to determine the maximum tolerated dose and safety of a single dose of standardized powder extract, uniformly milled curcumin (C3 Complextrade mark, Sabinsa Corporation). Healthy volunteers were administered escalating doses from 500 to 12,000 mg. RESULTS: Seven of twenty-four subjects (30%) experienced only minimal toxicity that did not appear to be dose-related. No curcumin was detected in the serum of subjects administered 500, 1,000, 2,000, 4,000, 6,000 or 8,000 mg. Low levels of curcumin were detected in two subjects administered 10,000 or 12,000 mg. CONCLUSION: The tolerance of curcumin in high single oral doses appears to be excellent. Given that achieving systemic bioavailability of curcumin or its metabolites may not be essential for colorectal cancer chemoprevention, these findings warrant further investigation for its utility as a long-term chemopreventive agent.

Administration, Oral↗

Epidemiologic and viral factors associated with cervical neoplasia in HPV-16-positive women.

While infection with high-risk HPV is the most important risk factor for cervical cancer, HPV alone is insufficient. Our purpose was to identify viral and epidemiologic factors associated with cervical disease in HPV-16 DNA-positive women referred to colposcopy. We used a standardized interview to collect epidemiologic data from consenting women. Total nucleic acids from exfoliated cervical cells were used for all viral assays (HPV detection and typing using L1 consensus PCR with line probe hybridization, variant classification by sequencing, viral load and transcript copy determination by quantitative PCR and transcript pattern by nested RT-PCR). Cervical disease was based on colposcopic biopsy. Logistic regression was used to calculate ORs with 95% CIs. There were 115 HPV-16 positive women among 839 enrollees. By univariate analyses, age >25 years (OR = 3.05, 95% CI 1.20-7.76), smoking (OR = 3.0, 95% CI 1.19-7.56), high viral load (OR = 5.27, 95% CI 2.05-13.60), detection of both E6 and E6*I transcripts (OR = 10.0, 95% CI 2.1-47.58) and high transcript copies (OR = 5.56, 95% CI 2.05-13.60) were significant risk factors for CIN III with reference to No CIN/CIN I. Less than a third of the women (31.5%) had prototype HPV-16 detected, and variants showed no association with disease, viral load or transcription. Viral DNA and transcript copies were highly correlated, and the ratio of transcript copies to DNA copies was not changed with disease status. While viral load, transcript copies and transcript pattern were statistically associated with CIN III, none of these measures effectively discriminated between HPV-16 women with disease requiring treatment and those who could be followed. Cellular proliferation and differentiation pathways affected by HPV should be investigated as biomarkers for cervical cancer screening.

Adolescent↗

Gene expression profile of cervical tissue compared to exfoliated cells: impact on biomarker discovery.

BACKGROUND: Exfoliated cervical cells are used in cytology-based cancer screening and may also be a source for molecular biomarkers indicative of neoplastic changes in the underlying tissue. However, because of keratinization and terminal differentiation it is not clear that these cells have an mRNA profile representative of cervical tissue, and that the profile can distinguish the lesions targeted for early detection. RESULTS: We used whole genome microarrays (25,353 unique genes) to compare the transcription profiles from seven samples of normal exfoliated cells and one cervical tissue. We detected 10,158 genes in exfoliated cells, 14,544 in the tissue and 7320 genes in both samples. For both sample types the genes grouped into the same major gene ontology (GO) categories in the same order, with exfoliated cells, having on average 20% fewer genes in each category. We also compared microarray results of samples from women with cervical intraepithelial neoplasia grade 3 (CIN3, n = 15) to those from age and race matched women without significant abnormalities (CIN1, CIN0; n = 15). We used three microarray-adapted statistical packages to identify differential gene expression. The six genes identified in common were two to four fold upregulated in CIN3 samples. One of these genes, the ubiquitin-conjugating enzyme E2 variant 1, participates in the degradation of p53 through interaction with the oncogenic HPV E6 protein. CONCLUSION: The findings encourage further exploration of gene expression using exfoliated cells to identify and validate applicable biomarkers. We conclude that the gene expression profile of exfoliated cervical cells partially represents that of tissue and is complex enough to provide potential differentiation between disease and non-disease.

Biomarkers↗

Recruitment and retention of economically underserved women to a cervical cancer prevention trial.

This review contrasts the planned and actual recruitment and retention efforts for a cervical cancer prevention study within a predominantly underserved population. Recruitment was a primary obstacle to trial progression and multiple strategies to improve recruitment were implemented to meet objectives. The actual recruitment strategies were expansion to five geographically distinct clinical sites, use of nurse practitioners focused primarily on patient issues, extremely flexible study hours and location, honorariums, support for transportation and child care, and creativity in maintaining contact with study participants. With these strategies, 90% of eligible patients consented to participate in the study.

Adult↗

Effects of low dose aspirin (81 mg) on proliferating cell nuclear antigen and Amaranthus caudatus labeling in normal-risk and high-risk human subjects for colorectal cancer.

Epidemiological, experimental, and clinical observations provide support for a colorectal cancer chemopreventive role for aspirin. We have evaluated the effects of aspirin on proliferation biomarkers in normal-risk and high-risk human subjects for colorectal cancer. Colorectal biopsies were obtained at baseline and at 24h after 28 daily doses of 81 mg of aspirin from 13 high-risk and 15 normal-risk subjects for colorectal cancer. We evaluated aspirin's effects on proliferating cell nuclear antigen (PCNA) immunohistochemistry and epithelial mucin histochemistry using the lectin, Amaranthus caudatus agglutinin (ACA) in crypt sections from rectal biopsies. The baseline whole crypt PCNA LIs differed significantly between normal-risk and high-risk subjects. PCNA LIs are not affected by 28 days of aspirin at 81 mg daily. ACA LIs are decreased by 28 days of aspirin at 81 mg daily in both normal-risk and high-risk subjects. Aspirin's effects on ACA LIs may have mechanistic and biological implications that deserve further attention. PCNA and ACA LIs are not useful as proliferation biomarkers for aspirin's chemopreventive activity in morphologically normal human colorectal mucosa.

Adult↗

Interventions fail to increase cancer screening rates in community-based primary care practices.

BACKGROUND: Cancer screening in primary care offices is reaching only a modest percentage of adults 50 years and older. The objectives of this study were to determine if screening rates for breast, cervical, and colorectal cancer could be significantly increased by two simple office interventions in community-based primary care offices and then maintained over 3 years. METHODS: Twenty-two community-based primary care practices were divided randomly into four arms: control, practice-based intervention, patient-based intervention, and both interventions combined. At baseline and annually for 3 years, medical records from approximately 100 male and 100 female patients 50 years and older were randomly selected. The outcome measures were screening rates for mammogram, Pap smear, fecal occult blood test, and flexible sigmoidoscopy or other colonic imaging. RESULTS: Generally each study arm evidenced a significant 1-year increase in screening rates, followed by an overall decline to approximate baseline levels. The first year increases in screening were not related to either invention, alone or in combination. CONCLUSIONS: These interventions do not have a significant impact on cancer screening rates in adults over several years. A variety of possible variables may have affected the long-term outcomes.

Adult↗

Developing a Web site in primary care.

BACKGROUND AND OBJECTIVES: While content, navigability, and usability are essential qualities of effective Web sites, the health care literature contains limited discussion of these issues. This article describes how knowledge gained through focus groups, Web site searches, and individual interviews were used to develop and improve a health-related Web site. METHODS: We conducted 10 focus groups and searches of existing Web sites in preparation for developing a Web site about colorectal cancer (CRC) screening. We conducted 30 in-depth interviews to assess content, navigation, and usability of a new CRC Web site, using participants recruited from Michigan communities with a low incidence of CRC testing. Targeted participants were 50-70 years of age, had no prior experience with CRC testing, and had variable comfort levels with Internet use. RESULTS: Existing CRC screening Web sites uniformly use user-directed navigation and have little variation in content. Our study participants stimulated revisions in content, navigation, and usability. Revised content factors included comprehension, utility, and appeal. Navigation changes focused on logical transition between sections. Usability changes included user focus and clarity of graphics/ text. CONCLUSIONS: We found focus groups, Web site searches, and individual interviews useful in developing and testing content, navigation, and usability of a CRC screening Web site. These steps provide methodological procedures for developing and revising health-related Web sites.

Aged↗

Low-dose topical delivery of all-trans retinoic acid for cervical intraepithelial neoplasia II and III.

OBJECTIVE: The objective of this study was to determine an effective dose for all-trans retinoic acid (atRA) delivered with a cervical cap and sponge for 4 days to women with cervical intraepithelial neoplasia (CIN) II/III. METHODS: Study participants made up of 175 women with biopsy-proven CIN II/III were randomized to four consecutive days of atRA at one of three doses (0.16%, 0.28%, and 0.36%) or placebo. All subjects underwent a repeat colposcopy evaluation and biopsy of the cervix at 12 weeks. RESULTS: The study participants mean ages were 27.6 years. The racial distribution was 63% Caucasian, 27% African American, and 8% other. Among participants, 93% were human papillomavirus-positive at baseline with 68% positive for high-risk types. The disease response at 12 weeks to atRA or placebo was not significantly different (P = 0.49) among the four dose groups. Participants with CIN II at baseline were more likely to be free of disease at 12 weeks than participants with CIN III at baseline (P = 0.003). There were no reported systemic adverse events related to drug or placebo exposure and only mild local self-reported and clinician-detected toxicities. CONCLUSION: Lower concentrations of atRA applied with a cervical cap for 4 days were no more effective than placebo. However, the rate of histologic regression in biopsied CIN II/III patients was high even over a short time interval, and emphasizes the importance of having a placebo arm and an adequate sample size.

Adolescent↗

Women's feedback on a chemopreventive trial for cervical dysplasia.

This study identifies the risks, benefits, and social influences affecting the decision to participate in a chemoprevention trial for cervical dysplasia. Women from three clinical sites in southeastern Michigan were invited to participate in a semi-structured interview. In previous studies, minority women have significant barriers to participation in clinical trials. However, in this study, women (63% black, 26% white, and 9% other ethnicity), were interested in participating and reported only moderate barriers. These barriers could easily be addressed with resources available to investigators.

Adult↗

Family physicians' knowledge of risk factors for cervical cancer.

BACKGROUND: A woman's risk for cervical cancer has been used by physicians to guide the initiation and frequency of a Pap smear. The aim of this study was to determine family physicians' knowledge of risk factors for cervical cancer and perceived importance of risk in screening women. METHODS: The self-administered questionnaire was mailed to 5000 randomly selected active members of the American Academy of Family Physicians (AAFP). RESULTS: Data from 2748 usable questionnaires indicated the mean number of risks considered for cervical cancer was 4.5. Physician's age and the number of reported risks were inversely correlated (p = 0.0001). Female physicians reported significantly more risk factors than male physicians (p = 0.05). The number of Pap smears performed per month was positively correlated with the number of risk factors reported (p = 0.001). Only 10% of the physicians indicated that they perform a Pap smear at the same interval regardless of the risk of the woman. CONCLUSIONS: This sample of family physicians has a limited understanding of the risk factors for cervical cancer. This was true regardless of the age, gender, training, race, geographic location, or practice setting of the responding physician. Yet the usual practice of screening for cervical cancer reported by these physicians would suggest that knowledge and use of risk factors would be a critical aspect of screening for cervical cancer.

Clinical Competence↗

Chaperone use by family physicians during the collection of a Pap smear.

BACKGROUND: We wanted to determine whether variations exist in use of a chaperone during the performance of a pelvic examination by family physicians. METHODS: A self-administered questionnaire was mailed to 5,000 randomly selected active members of the American Academy of Family Physicians. RESULTS: There were 3,551 survey responses (71% response rate) and 2,748 useable questionnaires. Most respondents (75.4%) reported routinely using a chaperone in the room during the collection of a Papanicolaou (Pap) smear. Significantly (P < .00001) more male physicians (84.1%) than female physicians (31.4%) reported using a chaperone. Physicians reporting routine use of a chaperone were significantly younger (P = .01) and did fewer Pap smears per month (P < .00001). Regional reporting of chaperone use varied significantly (P < .00001), with 71.6% reporting use in the Northeast, 89.0% in the South, 65.7% in the Midwest, and 72.4% in the West. CONCLUSION: Family physicians vary considerably in the reported use of a chaperone during the collection of a Pap smear. The variation could reflect different regional or local norms, efficiency or resource issues in high-volume clinical settings, or other interpersonal factors. These issues need to be explored in more depth.

Adult↗

Adults' knowledge and behaviors related to human papillomavirus infection.

BACKGROUND: Our objective was to assess adults' knowledge, risk behaviors, and preference for information about human papillomavirus (HPV). METHODS: A cross-sectional study using a self-administered questionnaire given in 3 locations (a university health service and 2 community family practice offices); 289 people completed the questionnaire. The primary outcome measure was a knowledge score calculated from the responses on specific items in the questionnaire. This knowledge score was developed by other investigators and has acceptable psychometric properties. RESULTS: Knowledge about HPV was low, with an average knowledge score of 5.50 (possible scores ranged from 0 to 14) and a mode of 0. Knowledge scores were significantly higher in women (P =.001) and married adults (P =.001). Knowledge scores were inversely related to age (P =.004) and positively correlated with years of education (P =.001) and self-assessment of knowledge (P <.001). Knowledge scores were positively correlated with condom use (P =.05) but not significantly associated with other risk behaviors. The most frequently desired time to receive information about HPV was before becoming sexually active. CONCLUSIONS: Adults seen in a typical family physician's office have limited knowledge of HPV. One tool family physicians can use to identify those with the least amount of knowledge is to ask patients how informed they are about HPV. The preferred time to receive information about HPV was before a patient became sexually active. However, it remains unclear whether educational intervention or knowledge changes risky behaviors.

Adult↗

Information technology and cancer prevention.

Information technology is rapidly advancing and making its way into many primary care settings. The technology may provide the means to increase the delivery of cancer preventive services. The aim of this systematic review is to examine the literature on information technology impacts on the delivery of cancer preventive services in primary care offices. Thirty studies met our selection criteria. Technology interventions studied to date have been limited to some type of reminder to either patients or providers. Patient reminders have been mailed before appointments, mailed unrelated to an appointment, mailed after a missed appointment, or given at the time of an appointment. Telephone call interventions have not used technology to automate the calls. Provider interventions have been primarily computer-generated reminders at the time of an appointment. However, there has been limited use of computer-generated audits, feedback, or report cards. The effectiveness of information technology on increasing cancer screening was modest at best. The full potential of information technology to unload the provider-patient face-to-face encounter has not been examined. There is critical need to study these new technologic approaches to understand the impact and acceptance by providers and patients.

Humans↗