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Biomedical subjects

G L Wied

Publications and source records attributed to G L Wied.

At least 37 records · Page 2Linked to original sources

Human papillomavirus standardization and DNA cytophotometry in cervical intraepithelial neoplasia.

Human papillomavirus (HPV) standardization and DNA cytophotometry were carried out in 29 cases of cervical intraepithelial neoplasia (CIN) grades I-III. A prognostically unfavorable DNA distribution pattern with an aneuploid stemline was found in 14 of the 16 dysplasias with HPV types 16 and 18, while in 11 of 13 dysplasias with HPV types 6 and 11 there was a favorable DNA distribution with a euploid-polyploid stemline. Among 178 colposcopically, cytologically and histologically confirmed cervical lesions, there was a statistically significant incidence of HPV 16/18 infections in severe dysplasias and carcinomas, while HPV 6/11 was found predominantly in mild cervical lesions. It seems that CIN can be divided into high- and low-risk lesions not only by the degree of severity and the DNA distribution pattern but also by HPV typing.

Adult↗

Quantitation of estrogen receptor content and Ki-67 staining in breast carcinoma by the microTICAS image analysis system.

The microTICAS image analysis system, originally designed for karyometry using Papanicolaou-stained or Feulgen-stained smears and tissue sections, has been adapted to assess tissue sections stained by immunohistochemical techniques. This system was used to quantitate growth fractions and the estrogen receptor (ER) content of breast carcinomas stained by immunoperoxidase techniques. The results were similar to those obtained with nonautomated methods of quantitating immunohistochemically stained tissue sections and, in the case of ER content, were similar to the results obtained with cytosol estrogen binding methods. The findings show that the microTICAS system provides an objective alternative to visual counting of labeled cells in tissue sections stained for growth fraction or for ER content by immunohistochemical methods.

Antibodies, Monoclonal↗

An interactive microcomputer-based system for the quantitative analysis of stratified tissue sections.

This paper describes a microcomputer-based system that allows diagnostically relevant properties of stratified tissue sections to be objectively measured. The results of detailed nuclear image analyses are examined in the broader context of the position of nuclei within the tissue section and relative to histologic structures and each other. Quantitative measures are obtained for important morphometric and densitometric properties of individual nuclei and mitotic figures and especially for their distribution and orientation within the tissue section relative to the stratum germinativum and each other. Recorded karyometric and histometric parameters include measures of nuclear DNA content (based on optical density measurements), size, roundness, texture, shape, distance to the basal layer, angle with the stratum germinativum, epithelial height and proximate nuclear distance. Statistics generated describe normalized mitotic density as a function of depth in the epithelium, and a composite mitotic index is produced based upon weighting of these densities relative to their distance from the stratum germinativum. These properties and derived statistics may be examined as a function of epithelial depth and nuclear type and may be plotted as a function of other diagnostic features in addition to the observed stratum. The system is one part of microTICAS-STRATEX, an expert diagnostic system for the clinical evaluation of stratified tissue sections, now under development as an outgrowth of the microTICAS system. Results of measurements made with this system will be compared with site-specific and diagnosis-specific reference profiles and used in conjunction with clinical data derived from a data base at the University of Chicago of over 1.5 million patients to generate diagnostic and prognostic evaluations.

Cell Nucleus↗

Karyometry and histometry of renal-cell carcinoma.

In an attempt to more objectively predict the outcome of renal cancers, karyometric and histometric studies were performed using an interactive computer-based system for the quantitative analysis of tissue sections. Analysis showed a significant relationship between patient survival and metastases and the histometric parameters of nuclear elongation, nuclear crowding and mitotic density, as well as tumor grade. Patients who died tended to have a high mitotic density, elongated and crowded nuclei and high-grade tumors. Ploidy showed no significant correlation with prognosis while nuclear elongation and crowding did. Differences in histologic grade were significantly associated with several histometric variables, including nuclear area, shape, crowding, elongation and mitotic density.

Adult↗

Rapid cytophotometry and its application to diagnostic pathology.

Computer processing of microscopic imagery of cervical lesions can provide novel quantitative diagnostic information. Interpretation of this information, from the level of the image itself to that of diagnostic truth, calls for the use of appropriate data structures. The resolution of the problems of diagnostic consensus and truth may be furthered by the use of these techniques in conjunction with diagnostic expert systems. The impact of our expanded ability to differentiate and to extract diagnostic and prognostic information will lead to changes in the way we practice clinical pathology. Technologic advances have now made it possible to perform quantitative measurements in a very rapid fashion as a practical part of routine clinical pathology activity.

Carcinoma↗

Markers for malignancy in the nuclear texture of histologically normal tissue from patients with thyroid tumors.

The chromatin of nuclei from histologically normal-appearing glands in tissue sections from patients with follicular adenoma, papillary carcinoma and follicular carcinoma of the thyroid exhibited changes that were statistically significant when compared to the nuclear chromatin in tissue sections of thyroid from normal individuals. Certain chromatin texture features assumed values approximating those found in tumor cell nuclei. Staining was affected only slightly, and morphometric features, such as nuclear area, roundness and ellipticity, were statistically not different from those in normal controls. In patients with Hürthle-cell tumors, such marker features could not be found. Results from measurements on 30 patients (approximately 1,000 nuclei) are reported.

Adenocarcinoma↗

Computer graphics in cytologic and pathologic microscopy. Tools for the clinician and researcher.

Computer graphics capabilities are becoming practical economically and ergonometrically for the first time on a widespread basis. The factors that have brought this about and the importance of such graphic interfaces to computer technology in the clinical and research laboratory are discussed. The uses of computer graphics in cytologic and pathologic microscopy are reviewed in terms of objectives, types of display and software and hardware display methods, and examples of various types of displays are presented.

Cell Nucleus↗

Differential diagnosis between follicular adenoma and follicular carcinoma of the thyroid by marker features.

Morphometric features descriptive of nuclear morphology, nuclear chromatin texture and nuclear staining density were studied in tissues from encapsulated follicular carcinoma and follicular adenoma of the thyroid, whose differentiation is one of the most difficult tasks in thyroid pathology. Measurements were made on nuclei in both tumorous and normal-appearing areas in the same section from six patients with each diagnosis, as well as on nuclei in sections from six normal individuals. The average nuclear optical density (OD) was significantly lower in the follicular carcinomas than in the follicular adenomas while the nuclear area was significantly increased in the carcinomas. The variance of the nuclear OD values was higher in both tumor and normal-appearing areas in the sections from the follicular adenomas than in the follicular carcinomas; this variance was lowest in tumor areas from the follicular carcinomas. There were also significant differences in another chromatin feature (the average difference in OD values between adjacent pixels) between nuclei from follicular carcinomas and those from follicular adenomas, whether comparing measurements between the tumor areas or between the histologically normal-appearing areas of the sections. These results suggest that the high-resolution study of marker features, such as nuclear chromatin and staining density, may help in the differentiation between follicular adenoma and encapsulated follicular carcinoma of the thyroid.

Adenocarcinoma↗

Correlation between automated DNA ploidy measurements of Hürthle-cell tumors and their histopathologic and clinical features.

The treatment of Hürthle-cell tumors of the thyroid is controversial because of their rarity and the inconsistent histopathologic criteria for their diagnosis. In order to obtain more objective criteria for the management of Hürthle-cell tumors, the nuclear DNA content of cells from 20 cases was measured with the MicroTICAS system and the correlation between the DNA distribution patterns and the clinical and histopathologic findings was evaluated. Three main DNA patterns were found: euploid, polyploid and aneuploid. The euploid or polyploid Hürthle-cell tumors came from patients who did not develop distant metastases or recurrence whereas the aneuploid variants came from patients who died of their disease and/or developed distant metastases and recurrence. Various correlation analyses were performed between DNA ploidy and age, sex, size of tumor, growth pattern, pleomorphism, invasion and metastases. Our data suggests that an aneuploid DNA pattern or one with a large percentage of aneuploid nuclei with DNA content exceeding 5N may predict eventual metastases or recurrence from Hürthle-cell tumor.

Adenoma↗

Software design for an inexpensive, practical, microcomputer-based DNA cytometry system.

Recent advances in digital electronics have made it possible to put together videophotometry systems capable of practical DNA ploidy measurements at a relatively modest cost. Such a system, based upon the IBM PC microcomputer and other "off-the-shelf" components, is now operational in our laboratory. This paper discusses the design considerations that went into the development of the software for this system. It examines the choices, constraints and tradeoffs involved in such a software engineering project and considers the practical implementation of image processing algorithms and a user-friendly interface. An overview is given of the modular, menu-driven software through which the system is controlled, along with a description of normal operational flow.

Cell Nucleus↗

MicroTICAS. The design of an inexpensive video-based microphotometer/computer system for DNA ploidy studies.

A description is presented of the microTICAS video-based microphotometer/computer system, which has been designed and implemented to provide an inexpensive means for the rapid assessment of DNA ploidy patterns. The design goal was to provide a low-cost, easily serviced unit capable of providing useful clinical results and that would be easy and convenient to use. The resulting system achieves those ends as well as providing a flexible research tool that can be extended with appropriate programming to perform a wide range of tasks. The major parts of the microTICAS system are the microscope/optical system, the video camera with its control unit, the video data digitizer, the frame buffer and display monitor and the small host computer. Commercially available components were chosen for these system components and have been assembled into a system with only a minimum of modifications. The resulting system can be configured to be compatible with both North American and European standards.

Computers↗

Evaluation of brush cytology as an independent technique for detection of esophageal carcinoma.

In this study the accuracy of indirect brush cytology for detection of esophageal carcinoma is evaluated against current standard methods of diagnosis and is compared with the known accuracy rate of endoscopically directed brush cytology. A standard endoscopic nylon brush placed inside a nasogastric tube was used in 203 patients with various esophageal problems. Correct diagnosis was made in 78% of cancers, 95% of potentially premalignant cases, and 100% of cases of normal esophageal mucosa with both indirect and directed brushing procedures. The technique meets most requirements of a new screening procedure as being simple, safe (no complications), relatively inexpensive, and acceptable to patients (98% compliance). Currently it is employed to monitor high-risk esophageal conditions and post-treatment courses of patients with pharyngoesophageal tumors for local recurrence or a new primary lesion in the esophagus.

Adenocarcinoma↗

Computer grading of cervical intraepithelial neoplastic lesions. I. Cytologic indices.

In an attempt to derive a computer-assisted grading for cervical intraepithelial neoplastic (CIN) lesions, apparent discrepancies with the visual diagnostic evaluation could be explained from the data structure of the objective assessment. The 40 cases of dysplasia in this study appeared to fall into two subgroups having different curves of progression. A smaller subgroup, visually graded as milder, less-severe CIN, exhibited dysplastic cells with unexpectedly high abnormality indices. A larger subgroup showed dysplastic cells with abnormality indices in agreement with the tissue assessment.

Computers↗

Ploidy measurements by high-resolution cytometry.

Technology has made DNA ploidy assessment a clinically and economically feasible procedure, 30 years after its clinical potential was established. This paper reviews the history of ploidy measurements, DNA cytophotometry, DNA interpretation and the prognostic value of nuclear DNA analysis in various anatomic sites. Emphasis is placed on static high-resolution cytometry, not flow cytometric methods, with a description given of the systems for rapid DNA cytometry developed as part of the TICAS Project at the University of Chicago.

Carcinoma↗

Ploidy patterns in cervical dysplasia.

The ploidy patterns determined for groups of patients with cervical dysplasia (cervical intraepithelial neoplasia [CIN]) were subjected to statistical analysis. The patterns were based on the measurement of at least 100 Feulgen-stained nuclei from 30 patients with normal cervices, 10 cases of CIN I, 18 cases of CIN II and 33 cases of CIN III. The scale of the patterns was a log transformation of the ratio of the total extinction (optical density) of the nuclei to that of the 2N reference; this widens the intervals for higher ploidies, alleviating sampling requirements for intervals in which occurrences are rare and helping to maintain a reasonable sample size-to-dimensionality ratio. Pairwise discriminant analyses showed clear distinctions between the ploidy pattern for normal cases and those for CIN I, CIN II and CIN III. The distinctions between the different grades of CIN, based on these modest sample sizes, were less clearcut, largely due to pronounced patient-to-patient variability. Analysis of variance confirmed that the patient groups constitute statistically distinct entities. An aneuploid pattern did not seem to develop until CIN III lesions were involved. The diagnostic and prognostic significance of these preliminary findings require further study using larger data sets and correlations to patient survival.

DNA↗

Transrectal aspiration biopsy versus transperineal core biopsy for the diagnosis of carcinoma of the prostate.

Transrectal aspiration and transperineal core biopsies were performed on 38 patients with suspicious prostatic examinations. The false negative rate was 14 per cent by the core method but no cancer was missed by the aspiration technique. There was insufficient material for diagnosis in 14 per cent of the biopsies obtained by the core technique but in only 3 per cent with the aspiration biopsy method. Malignant cells were confirmed by cytology in 1 patient who had had 2 normal core biopsies. The cytological grade was only moderately consistent with the Gleason sum. No complications developed after either procedure. Transrectal aspiration biopsy offers several advantages over conventional biopsy methods and should be used regularly to diagnose abnormalities of the prostate.

Adenocarcinoma↗

Intermediate cell markers for malignancy. Consistency of expression.

Studies of samples from a larger patient population confirmed the consistency of expression of the previously reported markers for malignancy in normal-appearing intermediate cervical cells in samples from patients with abnormal cytology (moderate dysplasia and severe dysplasia/carcinoma in situ). Based on samples of only 30 cells per case, a false-negative rate of 10% to 30% was estimated. The expression of the marker features thus provides a clear indication of uterine abnormal cytology; the lack of expression, however, does not entirely rule out the possibility of uterine abnormalities. The use of larger sample sizes and better staining protocols could further enhance the usefulness of marker feature studies in the prescreening for cancer.

Carcinoma in Situ↗