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Biomedical subjects

James Ranger-Moore

Publications and source records attributed to James Ranger-Moore.

33 records · Page 2Linked to original sources

Provider counseling, health education, and community health workers: the Arizona WISEWOMAN project.

BACKGROUND: The Arizona Well-Integrated Screening and Evaluation for Women Across the Nation (WISEWOMAN) project used provider counseling, health education, and community health workers (CHWs) to target chronic disease risk factors in uninsured, primarily Hispanic women over age 50. METHODS: Participants were recruited from two Tucson clinics participating in the National Breast and Cervical Cancer Early Detection Program (NBCCEDP). Women were randomly assigned into one of three intervention groups: (1) provider counseling, (2) provider counseling and health education, or (3) provider counseling, health education, and CHW support. At baseline and 12 months (1998-2000), participants were measured for height, weight, waist and hip circumference, and blood pressure. Blood tests were conducted to check blood glucose, cholesterol, and triglyceride levels. At each time point, participants also completed 24-hour dietary recalls and questionnaires focusing on their physical activity levels. RESULTS: A total of 217 women participated in baseline and 12-month follow-up. Three fourths were Hispanic. All three intervention groups showed an increase in self-reported weekly minutes of moderate-to-vigorous physical activity, with no significant differences between the groups. Significantly more women who received the comprehensive intervention of provider counseling, health education, and CHW support progressed to eating five fruits and vegetables per day, compared with participants who received only provider counseling or provider counseling plus health education. CONCLUSIONS: All three interventions increased moderate-to-vigorous physical activity but not fruit and vegetable consumption. The intervention group with provider counseling, health education, and CHW support significantly increased the number of women meeting national recommendations for fruit and vegetable consumption.

Aged↗

Contrast-enhanced sonography helps in discrimination of benign from malignant adnexal masses.

OBJECTIVE: To investigate the potential efficacy of real-time contrast-enhanced power Doppler sonography in the differentiation of benign and malignant adnexal masses in a pilot study. METHODS: Before surgical treatment, adnexal masses were prospectively evaluated with power Doppler sonography before and after injection of a contrast agent. Real-time postinjection sequences were computerized with time-intensity analysis software to determine an enhancement curve and contrast parameters. The intraobserver and interobserver reproducibilities of these criteria were assessed on a subsample. These contrast parameters were compared between benign and malignant tumors using logistic regression. Sensitivity and specificity were used to compare contrast parameters with sonographic and Doppler variables. RESULTS: Ninety-nine women were included, for a total of 101 adnexal masses. There were 23 cases of ovarian malignancies and 78 benign adnexal lesions. Our procedure had excellent intraobserver and interobserver reproducibility, with an average intraclass correlation coefficient of 0.92. The time before enhancement and intensity ratio did not reliably differentiate between the benign and malignant masses. Washout times and areas under the curves were significantly greater in ovarian malignancies than in other benign tumors (P < .001), leading to sensitivity estimates between 96% and 100% and specificity estimates between 83 and 98%. Contrast parameters had slightly higher sensitivity and slightly lower specificity when compared with transvaginal sonographic variables of the resistive index and serum cancer antigen 125 levels. CONCLUSIONS: Contrast-enhanced power Doppler imaging may easily and precisely discriminate benign from malignant adnexal lesions. Larger studies are needed to determine the appropriate use and benefits of this new procedure.

Adnexal Diseases↗

Karyometric image analysis for intraepithelial and invasive cervical lesions.

OBJECTIVE: To derive an objective, numeric measure for the progression of intraepithelial and invasive squamous cell cervical lesions. STUDY DESIGN: Thin-layer cervical cytology preparations from colposcopically confirmed normal cervix, low grade squamous intraepithelial lesions, high grade squamous intraepithelial lesions and carcinoma were identified from a cross-sectional study. Fifty-nine cases representing 4 diagnostic categories were selected, and 2,375 nuclei from epithelial cells representative of the diagnostic category were randomly selected for imaging and measurement from these cases. Additionally, 1,378 visually normal appearing intermediate cells from low and high grade squamous intraepithelial lesions, as well as from carcinoma cases, were identified for analysis. The nuclei were quantitatively characterized, and discriminant analyses were performed to derive a progression curve from normal cytology to carcinoma. RESULTS: The lesion signatures show a clear increase in nuclear abnormality with increasing progression. A progression curve was derived based on mean discriminant function scores for each diagnostic category and on the mean nuclear abnormality values for the nuclei in each category, as expressed by their deviation in feature values from normal reference nuclei. CONCLUSION: A numeric assessment of lesion progression for cervical precancerous and cancerous lesions based on karyometric measurements is possible and may provide an objective, precise characterization of each lesion as well as a basis for improved performance in automated cytology-based cervical cancer screening.

Cell Nucleus↗

Karyometric analysis of actinic damage in unexposed and sun-exposed skin and in actinic keratoses in untreated individuals.

OBJECTIVE: To assess the ability of karyometric analysis to demonstrate progression of actinic damage as a function of sun exposure in individuals with actinic keratoses (AKs) and to evaluate the stability of that assessment over a 3-month period. STUDY DESIGN: Biopsies from subjects with AKs were obtained from unexposed skin, sun-exposed skin and AK lesions. Subjects used an SPF 50 sunscreen, and 3 months later additional biopsies were taken from sun-exposed and AK sites. A total of 13,300 nuclei were recorded from 31 subjects. RESULTS: Measures of nuclear abnormality (NA) and effects of sun damage based on discriminant function (DF) scores were derived. Actinic damage levels varied significantly across biopsy site, demonstrating the method's sensitivity. Accrual of actinic damage was demonstrated in sun-exposed skin and AK lesions when all nuclei were examined over 3 months but only for sun-exposed skin when the worst-damaged nuclei were examined. This suggests a ceiling effect of nuclear damage in the progression to abnormality. Within-subject variability was similar for both NA and DF when all nuclei were considered. Among the worst-damaged nuclei (as defined by high DF), DF showed lower within-case variability than NA, perhaps due to a reduction in nuclear heterogeneity. CONCLUSION: Karyometry's ability to detect subtle levels of actinic damage in nuclear chromatin patterns may make it useful in screening agents for possible use in cancer chemoprevention.

Actins↗

Preneoplastic changes in ovarian tissues.

OBJECTIVE: To test whether histologically normal epithelium within ovarian inclusion cysts and stroma exhibit changes in nuclear chromatin pattern that indicate the presence of occult ovarian lesions. STUDY DESIGN: Ovaries were collected from 10 low-risk women,from 7 high-risk women and from 3 women with ovarian cancer. Histologic sections were cut at 5 microm and hematoxylin and eosin stained. High-resolution images were recorded from the epithelium lining inclusion cysts and from the underlying stroma of ovaries from these 20 subjects. A total of 2860 epithelial nuclei and 3610 stromal nuclei were recorded. Karyometric features and nuclear abnormality were computed. Discriminant analyses and unsupervised learning algorithms defined deviations from normal that were designated "above threshold" and used to compute average nuclear abnormality of a second nuclear phenotype. RESULTS: Histologically normal epithelium from inclusion cysts of ovaries harboring a malignant lesion was shown to exhibit changes in the nuclear chromatin pattern that were statistically significant using quantitative image analysis procedures. Similar changes were seen in the inclusion cyst epithelia of high-risk ovaries. A subpopulation of cells representing a new phenotype was detected in the underlying stroma of women harboring a malignant ovarian lesion and in women at high risk of ovarian cancer. CONCLUSION: The karyometric changes observed in the epithelia lining inclusion cysts and in the underlying stroma of ovaries either with ovarian cancer or at high risk of ovarian cancer suggest the presence of preneoplastic changes in histologically normal tissue.

Cell Nucleus↗

Circulating endogenous retinoic acid concentrations among participants enrolled in a randomized placebo-controlled clinical trial of retinyl palmitate.

Retinoids have been studied extensively for their chemopreventive properties. The biological activity of retinoids is acquired through their conversion to retinoic acid (RA). Characterization of endogenous circulating RA concentrations after supplementation with vitamin A over longer time periods has not been done previously. Our investigation was conducted to determine whether vitamin A (retinyl palmitate) supplementation significantly increases circulating RA concentrations of all-trans-, 9-cis-, and 13-cis-RA. Using plasma samples from 41 participants enrolled in a randomized clinical trial of placebo, 25,000, 50,000, or 75,000 IU supplemental retinyl palmitate daily, high-performance liquid chromatography analyses were conducted for concentrations of three RA isomers. Seven plasma samples were analyzed for each participant over a 16-month period. Based on an intention-to-treat analysis, results obtained using linear mixed models showed that supplementation with retinyl palmitate statistically significantly increased concentrations of all three RA isomers from baseline levels. This study suggests that supplementation with retinyl palmitate is an effective means to increase circulating all-trans, 9-cis-, and 13-cis-RA concentrations among humans.

Aged↗

Subvisual changes in chromatin organization state are detected by karyometry in the histologically normal urothelium in patients with synchronous papillary carcinoma.

This study analyzed the chromatin organization state in histologically normal urothelium in patients with synchronous papillary carcinoma using digital texture analysis. The quantitative evaluation was carried out on hematoxylin and eosin-stained sections from 17 cases of urothelial papillary carcinoma in which a simultaneous biopsy specimen featuring histologically normal urothelium was available. Five bladder biopsy specimens of histologically normal urothelium from patients with prostate pathology in whom cystoscopy revealed a normal bladder mucosa were also analyzed. Karyometry showed that the 17 cases of papillary carcinoma, morphologically classified according to the 1973 World Health Organization scheme, belonged to a continuous spectrum or trend curve spanning grade 1 to grade 3. An abnormal pattern and distribution of the nuclear chromatin was seen in the normal-looking urothelium from the 17 bladders with papillary lesions. When this population was plotted along the trend curve, it occupied an intermediate position between the normal samples and samples from grade 1 carcinoma. When the nuclei were considered individually, the changes were detected only in a subpopulation of nuclei with chromatin alteration pointing toward that seen in grade 1 cases, even though distinct from them. In conclusion, karyometry can detect an abnormal chromatin pattern and distribution in the normal-looking urothelium adjacent to papillary carcinoma. Such alterations correspond to the so-called "malignancy-associated change."

Carcinoma, Papillary↗

Efficacy of oral transmucosal nicotine lozenge for suppression of withdrawal symptoms in smoking abstinence.

Nicotine replacement therapy relieves withdrawal symptoms, significantly improving smoking cessation rates. Oral transmucosal nicotine (OT-NIC) is a novel nicotine delivery system consisting of a lozenge (OT-NIC unit) containing 4 mg of nicotine, which is dissolved in the cheek pouch, releasing nicotine for absorption through the buccal mucosa. Theoretical advantages of OT-NIC include that it does not require special chewing methods or interfere with dental work, it provides sensory oral effect, and it can be dosed to effect. This study aimed to determine the preliminary safety and efficacy of OT-NIC for suppression of nicotine withdrawal symptoms over 8 days of smoking abstinence and to assess flavor preference, sensory characteristics, and acceptability. In an open-label, within-subjects design, 11 smokers used three different flavors of OT-NIC ad lib in response to withdrawal symptoms and craving. On days 1 and 8, withdrawal symptoms were measured with pre- and postadministration scores for each of the first three OT-NIC units used (three different flavors presented in random order). Flavor preference, desire to smoke, sensory characteristics, acceptability, and overall OT-NIC performance were rated at the end of each day. A generalized estimating equation analysis was conducted to account for the repeated-measures design. Use of OT-NIC resulted in a significant decrease in a composite withdrawal score aggregating scores from all eight symptoms (decline of.57 units in a possible range of 4, p<.01). Withdrawal scores for anxiety, craving, difficulty concentrating, impatience, and restlessness significantly decreased. Depressed mood, increased appetite, and irritability did not change. Order of flavor preference was peppermint over cinnamon over plain. Acceptability and ratings for sensory characteristics were favorable, and OT-NIC was well tolerated with no serious adverse effects. In conclusion, OT-NIC showed promise as a potential new aid for smoking cessation.

Administration, Oral↗

Malignancy-associated changes in lactiferous duct epithelium.

OBJECTIVE: To determine whether cells from histologically normal appearing epithelium of the lactiferous duct from women with a remote ductal lesion in the breast provide any clues indicating the existence of such a lesion. STUDY DESIGN: Tissue sections cut to 4 microns and stained with hematoxylin and eosin were prepared from duct tissue of 20 women with breast lesions and of 20 women free of any such lesion who had undergone mammoplastic procedures or resection for benign reasons. One hundred nuclei were measured from each case. Measures of nuclear deviation from normal were computed, discriminant functions were derived, and multivariate significance tests were conducted. RESULTS: Nuclei from histologically normal appearing regions of lactiferous duct epithelium from women harboring distant lesions exhibited changes in the distribution pattern of their nuclear chromatin, indicating the presence of these lesions. The statistical significance of these changes was documented. The changes were clearly evident in all 20 subjects with lesions and were not observed in 19 of the 20 subjects without lesions. CONCLUSION: The results suggest that studies aimed at detecting malignancy-associated changes in cells collected by ductal lavage might lead to a minimally invasive screening procedure for breast lesions.

Adult↗

Expression of dominant negative c-jun inhibits ultraviolet B-induced squamous cell carcinoma number and size in an SKH-1 hairless mouse model.

UVB radiation is a complete carcinogen able to initiate, promote, and progress keratinocyte cells toward carcinogenesis. Exposure to UVB leads to the propagation of a number of signal transduction pathways resulting in increased DNA binding of transcription factors, including activator protein-1 (AP-1), and subsequent gene expression. To test the hypothesis that AP-1 activation plays a role in the promotion of UVB-induced skin tumors, a dominant negative c-jun (TAM67) mutant transgene was expressed in the epidermis of SKH-1 hairless mice and bred with mice expressing an AP-1 luciferase reporter gene. Single UVB exposure experiments showed a significant decrease in AP-1 activity, as measured by luciferase levels, in mice expressing TAM67 72 h postexposure. Transgenic and nontransgenic littermates were placed into a chronic UVB exposure experiment, three exposures per week for 25 weeks. Expression of TAM67 reduced the number of tumors per mouse by 58% and tumor sizes were 79% smaller than the tumors present in the nontransgenic study group. These tumors were histologically identified as squamous cell carcinomas. TAM67 had no effect on UVB-induced hyperplasia because comparable epidermal thickening was observed in both study groups over a 5-day period post-UVB exposure. Immunohistochemical analysis showed a reduction in the number of cyclin D(1)-expressing cells in squamous cell carcinoma samples removed from the TAM67 study group. These data show that TAM67 can inhibit UVB-induced squamous cell carcinoma formation, suggesting that AP-1 is a good candidate target for the development of new chemoprevention strategies to prevent sunlight-induced skin cancers.

Animals↗

Reliability and validity of a histologic score as a marker for skin cancer chemoprevention studies.

OBJECTIVE: To develop a reliable and valid scoring system for grading skin biopsies from actinic keratosis (AK) and sun-damaged skin for use in evaluating the efficacy of skin cancer chemopreventive agents. STUDY DESIGN: A panel of dermatopathologists developed histologic criteria and diagnostic definitions for the progression of lesions from early AK to AK. The criteria were then applied to a sample of 335 histologic slides from an ongoing chemoprevention study. A 10% sample of 35 slides was reread in order to assess intrarater reliability. RESULTS: Six of the 7 criteria demonstrated high reliability (> 85%). The total histologic score, calculated using the 6 criteria, was found to significantly differentiate between (blinded) biopsy location (normal, pre-AK, AK and adjacent to squamous cell carcinoma) and histologic diagnosis (normal, pre- or early AK, AK and squamous cell carcinoma). CONCLUSION: The total histologic score, having demonstrated reliability on repeated readings and validity in its association with biopsy location and histologic score, is a reliable and valid end point for judging the efficacy of agents in skin cancer chemoprevention studies. Additional interrater reliability tests utilizing larger test sets and a rigorous statistical design should be undertaken to establish its portability.

Biopsy↗

Karyometry of nuclei from actinic keratosis and squamous cell cancer of the skin.

OBJECTIVE: To use karyometric analysis methods to compare actinic keratoses (AKs) to squamous cell carcinomas (SCCs) to determine if SCCs showed a logical progression beyond that seen in AKs and to explore variability within and between lesion types to better understand distinctions between the 2. STUDY DESIGN: Biopsies from 31 subjects with AKs were obtained from upper inner arm skin, forearm skin and AK lesions. Biopsies from 23 different subjects in a related subproject provided SCC biopsies for comparison. RESULTS: Karyometric measures of nuclear abnormality and sun damage were derived. Mean actinic damage levels progressed logically from inner arm to sun-exposed skin, to AK, to SCC. Considerable heterogeneity existed at the case level. Unsupervised learning methods revealed 2 distinct clusters of progressed lesions with different nuclear signatures, reflecting differing levels of actinic damage. Number of AKs and SCCs and invasiveness and differentiation of SCCs were distributed across both clusters in roughly equivalent proportions. CONCLUSION: Karyometric methods, shown previously to be capable of sensitively detecting subtle nuclear changes, revealed the possibility of 2 progression pathways, each containing AKs and SCCs. This finding may have prognostic implications.

Adolescent↗

Statistical analysis of chemopreventive efficacy of vitamin A in sun-exposed, normal skin.

OBJECTIVE: To develop numeric, statistically secured measures of chemopreventive efficacy and to derive procedures with high sensitivity of detection. STUDY DESIGN: Karyometric features were computed for nuclei from the basal cell layer of biopsies taken from sun-exposed but histologically "normal" skin. Biopsies were collected from placebo-treated subjects and subjects treated for one year with daily, oral doses of 25,000, 50,000 and 75,000 IU of vitamin A. A total of 22,600 nuclei were recorded from 113 cases, at baseline and after one year. RESULTS: Two numeric measures of chemopreventive efficacy were applied: a measure of nuclear abnormality and a measure based on discriminant function scores. Both showed statistically significant chemopreventive effects of vitamin A. Dose-response curves were derived. A novel procedure, second order discriminant analysis, resulted in very high sensitivity for the detection of change in nuclear chromatin patterns. CONCLUSION: Karyometric analysis has increased in sensitivity such that changes on the order of 10%, found in only a low percentage of nuclei in a biopsy specimen, can be reliably documented. The methodology lends itself to cost-efficient screening of compounds for chemopreventive efficacy.

Biopsy↗

Changes in water mobility measured by diffusion MRI predict response of metastatic breast cancer to chemotherapy.

The goal of oncology is the individualization of patient care to optimize therapeutic responses and minimize toxicities. Achieving this will require noninvasive, quantifiable, and early markers of tumor response. Preclinical data from xenografted tumors using a variety of antitumor therapies have shown that magnetic resonance imaging (MRI)-measured mobility of tissue water (apparent diffusion coefficient of water, or ADCw) is a biomarker presaging cell death in the tumor. This communication tests the hypothesis that changes in water mobility will quantitatively presage tumor responses in patients with metastatic liver lesions from breast cancer. A total of 13 patients with metastatic breast cancer and 60 measurable liver lesions were monitored by diffusion MRI after initiation of new courses of chemotherapy. MR images were obtained prior to, and at 4, 11, and 39 days following the initiation of therapy for determination of volumes and ADCw values. The data indicate that diffusion MRI can predict response by 4 or 11 days after commencement of therapy, depending on the analytic method. The highest concordance was observed in tumor lesions that were less than 8 cm3 in volume at presentation. These results suggest that diffusion MRI can be useful to predict the response of liver metastases to effective chemotherapy.

Adult↗

Effectiveness of the nicotine inhaler for smoking cessation in an OTC setting.

OBJECTIVE: To evaluate the effectiveness of the Nicotrol nicotine inhaler as an aid to smoking cessation in over-the-counter (OTC) versus health-care-provider (HCP) conditions. METHODS: Five hundred twenty healthy smokers were randomized to the treatment conditions and followed for a year. RESULTS: At most follow-up visits, abstinence rates for the HCP group were 2 to 3 times those observed in the OTC group. Abstinence at 1 year was.77% in the OTC condition versus 3.08% in the HCP condition [P<.01]. Inhaler use was low. CONCLUSIONS: OTC nicotine inhaler appears to be ineffective, though quit rates are improved with HCP assistance.

Administration, Inhalation↗