Biomedical subjects

M Follen

Publications and source records attributed to M Follen.

25 records · Page 2Linked to original sources

PubMed2000

Laser scanning confocal microscopy of cervical tissue before and after application of acetic acid.

OBJECTIVES: The use of high-resolution in vivo confocal imaging may offer a clinically useful adjunct to standard methods for the diagnosis and screening of epithelial precancers. This study assesses the feasibility of real-time confocal reflectance imaging of cervical tissue and the use of acetic acid as a contrast agent to increase visualization of cell nuclei. STUDY DESIGN: A confocal microscope was used to image cervical cells and colposcopically normal and abnormal cervical biopsy specimens. Images were obtained before and after the application of 6% acetic acid. RESULTS: The confocal imaging system resolved subcellular detail throughout the entire epithelial thickness. Normal and abnormal tissues were clearly able to be differentiated. Addition of acetic acid enhanced nuclear signal in all acquired images. CONCLUSION: High-contrast reflected light images of cervical tissue are attainable in near real time. Acetic acid significantly increases light scattering from cell nuclei, which may partially explain why acetowhitening occurs.

Acetic Acid↗

PubMed2000

Autofluorescence patterns in short-term cultures of normal cervical tissue.

Fluorescence spectroscopy has potential to improve cervical precancer detection. The relationship between tissue biochemistry and fluorescence is poorly understood. The goal of this study was to characterize normal cervical autofluorescence, using fresh tissue short-term tissue cultures and epithelial cell suspensions. Transverse, short-term tissue cultures were prepared from 31 cervical biopsies; autofluorescence images were obtained at 380 and 460 nm excitation. Fluorescence excitation-emission matrices were measured from normal, precancerous and cancerous cervical cell suspensions. Observed fluorescence patterns contrast those reported for frozen-thawed tissue, and were placed into groups with (1) bright epithelial and weak stromal fluorescence; (2) similar epithelial and stromal fluorescence; and (3) weak epithelial and bright stromal fluorescence. The average ages of women in the groups were 30.9, 38.0 and 49.2 years. Epithelial fluorescence intensity was similar in Groups 1 and 2, but weaker in Group 3. Stromal intensity was similar in Groups 2 and 3, but weaker in Group 1. The ratio of epithelial to stromal fluorescence intensity was significantly different for all groups. EEMs of cell suspensions showed peaks consistent with tryptophan, reduced form of nicotinamide adenine dinucleotide (phosphate) and flavin adenine dinucleotide. Short-term tissue cultures represent a novel, biologically appropriate model to understand cervical autofluorescence. Our results suggest a biological basis for the increased fluorescence seen in older, postmenopausal women.

Adult↗

PubMed1999

Synthesis of IFN-gamma by CD8(+) T cells is preserved in HIV-infected women with HPV-related cervical squamous intraepithelial lesions.

OBJECTIVE: The aim of this study was to investigate whether coinfection with HIV affects the synthesis of Th1 and Th2 cytokines by peripheral blood T cells of women infected with human papillomavirus (HPV). METHODS: Cervical swabs and peripheral blood were obtained from women referred for colposcopy. HPV DNA by Digene's hybrid capture assay, HIV RNA by Roche's Amplicor assay, and cytokine synthesis of T-cell subsets by flow cytometry were assessed. HPV-associated cervical and HIV-associated immune deficiency diseases were staged using the Bethesda System and the Centers for Disease Control criteria, respectively. RESULTS: Patients with HIV and/or HPV infections had lower percentages of IL-2(+) and higher percentages of IL-10(+) T cells than healthy women. Furthermore, women with both virus infections (HIV(+)/HPV(+)) had significantly fewer IL-2(+) CD4(+), IFN-gamma(+) CD4(+), and TNF-alpha(+) CD4(+) T cells than women with HPV infection alone (HPV(+)). Whereas HIV(+) and healthy women had similar numbers of IFN-gamma(+) CD8(+) T cells, HPV(+) women had significantly fewer IFN-gamma(+) CD8(+) T cells than healthy women. CONCLUSION: HIV infection adversely affects the synthesis of Th1 cytokines by CD4(+), but not IFN-gamma synthesis by CD8(+) T cells of women with active HPV infection. The increase in IFNgamma(+) CD8(+) T cells, a phenotype consistent with cytotoxic T lymphocytes, may account for the stable HIV disease of the women studied. However, the increase in IFN-gamma(+) CD8(+) T cells is less likely to be HPV-specific as there was a higher incidence of HPV-related cervical SIL in HIV(+)/HPV(+) women compared with HPV(+) women.

Adolescent↗

PubMed1999

A comparison of C/B ratios from studies using receiver operating characteristic curve analysis.

In receiver operating characteristic (ROC) curve analysis, the optimal cutoff value for a diagnostic test can be found on the ROC curve where the slope of the curve is equal to (C/B) x (1-p[D])/p[D], where p[D] is the disease prevalence and C/B is the ratio of net costs of treating nondiseased individuals to net benefits of treating diseased individuals. We conducted a structured review of the medical literature to examine C/B ratios found in ROC curve analysis. Only two studies were found in which a C/B ratio was explicitly calculated; in another 11 studies, a C/B ratio was based on a so-called holistic estimate, an all-encompassing educated estimate of the relative costs and benefits relevant to the clinical situation. The C/B ratios ranged from 0.0025 (tuberculosis screening) to 2.7 (teeth restoration for carious lesions). Clinical scenarios that are directly life threatening but curable had C/B ratios of less than 0.05. This analysis led us to construct a table of ordered C/B ratios that may be used by investigators to approximate C/B ratios for other clinical situations in order to establish cutpoints for new diagnostic tests.

Clinical Laboratory Techniques↗

PubMed1999

Image morphometric nuclear grading of intraepithelial neoplastic lesions with applications to cancer chemoprevention trials.

A new image morphometric method of nuclear grading is described and assessed in the context of the evaluation of histological samples from ductal carcinoma in situ of the breast and cervical intraepithelial neoplasia. The method results in a continuous scaled variable, or nuclear grading scale, expressed in SD units from measured normal nuclei from breast or cervix. For a given histological preinvasive neoplastic lesion, the mean nuclear grade of measured nuclei was shown to be analogous to the histopathological nuclear grade of the same lesion assigned subjectively by the pathologist. In a chemoprevention trial of the effect of difluoromethylornithine given for 1 month to subjects with cervical intraepithelial neoplasia grade 3, pathologists could see no difference in 14 histological sections taken before and after difluoromethylornithine treatment. However, the image morphometric method detected a systematic effect of lowered mean nuclear grade and a decrease in the variability of nuclear grade expression. Twelve of 14 samples showed a lower posttreatment mean nuclear grade (P<0.05), and 13 of the 14 samples showed a decrease in the SD of their nuclear grade distributions (P<0.01). This study demonstrates the use of image morphometric nuclear grading in a chemoprevention setting. It may be very useful in supplementing the pathologist's histopathological grading by providing objective, quantitative assessments.

Antineoplastic Agents↗

PubMed1996

Generalizability of clinical studies conducted at tertiary care medical centers: a population-based analysis.

The Marshfield Epidemiologic Study Area (MESA), a geographically defined population registry at one of the participating sites in SUPPORT (a multicenter study of the care of seriously ill hospitalized patients) permitted assessment of generalizability in that study. On the basis of age- and sex-specific rates of enrollment of SUPPORT patients in MESA, we estimate that about 400,000 patients per year would fulfill SUPPORT eligibility criteria in the United States. However, an estimated 925,000 patients, particularly the elderly and those with impairments in their activities of daily living (ADLs), have SUPPORT-like illnesses annually, but do not receive the aggressive care required for study enrollment. The absence of patients not interested in aggressive care in tertiary care-based studies is compounded by the overrepresentation of patients referred from distant areas to the tertiary care center. Such patients tended to be older and to have different diseases than patients in MESA. Care should be taken in generalizing results from clinical and epidemiologic studies conducted at tertiary care centers.

Aged↗

PubMedDate not supplied

A pilot study for a screening trial of cervical fluorescence spectroscopy.

Fluorescence spectroscopy is a promising technology for detection of epithelial precancers and cancers. In preparation for a multicenter phase II screening trial, a pilot trial was conducted to test data collection and patient examination procedures, use data forms, time procedures, and identify problems with preliminary data analysis. Women 18 years of age and older underwent a questionnaire, a complete history, and a physical examination, including a pan-colposcopy of the lower genital tract. A fiber-optic probe measured fluorescence excitation-emission matrices at 1-3 cervical sites for 58 women. The data collection procedures, data forms, and procedure times worked well, although collection times for all the clinical data take an average of 28 min. The clinical team followed procedures well, and the data could be retrieved from the database at all sites. The multivariate analysis algorithm correctly identified squamous normal tissue 99% of the time and columnar normal tissue only 7%. The assessment of ploidy from monolayer samples was not accurate in this small sample. The study was successful as a pilot trial. We learned who participated, who withdrew, how often abnormalities were present, and that algorithms that have worked extremely well in previous studies do not work as well when a few study parameters are changed. The current algorithm for diagnosis identified squamous normal tissue very accurately and did less well for columnar normal tissue. Inflammation may be an explanation for this phenomenon. Fluorescence spectroscopy is a promising technology for the detection of epithelial precancers and cancers. The screening trial of fluorescence and reflectance spectroscopy was successful.

Adult↗