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Biomedical subjects

E B King

Publications and source records attributed to E B King.

At least 19 recordsLinked to original sources
PubMed1992

Breast cancer incidence in women with abnormal cytology in nipple aspirates of breast fluid.

This is a prospective study of breast cancer risk in relation to nipple aspirate fluid cytology in 2,701 volunteer white women from the San Francisco Bay Area first enrolled between 1973 and 1980. The women were not pregnant or lactating and were free of breast cancer within 6 months of entry into the study. The breast cancer status of this cohort was determined between June 1988 and April 1991. Follow-up was complete for 87% (n = 2,343) of the cohort, representing 29,961 person-years and an average of 12.7 years of follow-up. The overall breast cancer incidence was 4.4% (104 of 2,343) and rose with fluid cytology findings as follows: no fluid obtained, 2.6% (9 of 352); unsatisfactory specimen, 4.8% (15 of 315); normal cytology, 4.3% (56 of 1,291); epithelial hyperplasia, 5.5% (18 of 327); and atypical hyperplasia, 10.3% (6 of 58). Relative risks for breast cancer and their 95% confidence intervals were estimated by Cox regression, adjusting for age and year of entry. Compared with the relative risk for women who yielded no fluid, relative risks were: unsatisfactory specimen, relative risk (RR) = 1.4 (95% confidence interval (CI) 0.6-3.3); normal cytology, RR = 1.8 (95% CI 0.9-3.6); epithelial hyperplasia, RR = 2.5 (95% CI 1.1-5.5); and atypical hyperplasia, RR = 4.9 (95% CI 1.7-13.9). These findings were strongest for and were mainly confined to women aged 25-54 years. Women with atypical hyperplasia and a first-degree family history of breast cancer were six times more likely to develop breast cancer than were women with atypical hyperplasia but without a family history of breast cancer (95% CI 1.0-30.2). These findings provide strong support for our hypothesis that hyperplasia and atypical hyperplasia diagnosed in nipple aspirates of breast fluid are associated with an increased risk of breast cancer.

Adolescent↗
PubMed1991

Characterization by image cytometry of duct epithelial proliferative disease of the breast.

To develop a morphometric model of premalignant breast epithelium, we evaluated 120 lesions classified as nonproliferative disease (n = 20), hyperplasia (n = 20), moderate hyperplasia (n = 20), atypical hyperplasia (n = 20), carcinoma in situ (n = 20), and carcinoma (n = 20) in tissue from surgical biopsy or mastectomy. Atypical hyperplasia, a component of duct epithelial proliferative disease, has frequently been described in breasts with carcinoma. Atypical hyperplasia is generally viewed as premalignant or as a marker of increased risk for breast cancer. Measurements of nuclei in breast lesions were obtained with the Leitz TAS Plus on 4-microns sections stained for DNA with the Azure A Feulgen reaction. Nuclei of duct epithelial lesions had morphometric features that displayed changes from nonproliferative disease to carcinoma. The morphometric data from each lesion were compared among the six disease groups. Means of nuclear area, perimeter, maximum and minimum diameter, and large dark and large light intranuclear areas increased with higher degrees of proliferative abnormality. When the six groups of lesions were compared using the means of the first four nuclear features, atypical hyperplasia was significantly different (P less than 0.05) from carcinoma and non-proliferative lesions, but not from hyperplasia, moderate hyperplasia, or carcinoma in situ. These findings suggest that objective morphometric descriptors for characterizing significant proliferative lesions can be established using image cytometry. The progressive increases also suggest that proliferative breast disease is a continuum that includes premalignant lesions.

Azure Stains↗
PubMed1990

Cerumen phenotype and proliferative epithelium in breast fluids of U.S.-born vs. immigrant Asian women: a possible genetic-environmental interaction.

To determine whether a genetic-environmental interaction exists between the breast, a modified apocrine gland, its secretions, and the genetic polymorphic phenotypes of wet and dry cerumen, we examined nipple aspirate fluid (NAF) for proliferative disease in 172 U.S.-born and immigrant Chinese and Japanese women. Cytologic evidence of proliferative epithelial cells (benign hyperplasia and/or atypical hyperplasia) was found in the NAF of 36 women (20.9%). A significantly higher incidence of proliferative epithelial cells was present in the NAF of U.S.-born than in immigrant Asian women (28.6% vs. 16.5%) (p = 0.05). A higher proportion of U.S.-born Asian women with wet cerumen than women with dry cerumen had proliferative epithelial cells in NAF: 39.3% vs. 20.0% (p = 0.08). No significant difference in NAF proliferative cells was found between immigrant women with wet and dry cerumen: 15.8% vs. 17.3%; p = 0.50. A strong association of proliferative epithelial cells and cerumen phenotype was found in parous U.S.-born women (wet = 47.6% vs. dry = 16.0%; p = 0.002). No significant association with wet and dry cerumen phenotype was found in parous immigrant women (wet = 12.2% vs. dry = 20%). These findings support the hypothesis that an apocrine genetic polymorphic trait differentially influences susceptibility of the breast to proliferative disease in Asian women born in environments presumed to be of high risk for breast cancer compared to women from low risk environments.

Body Fluids↗
PubMed1990

Factors associated with obtaining nipple aspirate fluid: analysis of 1428 women and literature review.

Studies of cytologic and biochemical constituents of nipple aspirates of breast fluid have contributed to understanding the natural history of benign and malignant breast disease. We conducted multivariate analyses using 1428 women from a recent case-control study of breast disease to determine which factors were independently associated with the ability to obtain breast fluid from nonlactating women. We then compared results from these analyses to the results from five previous studies that also used the aspiration technique of Sartorius. Four factors were consistently associated across studies with increased ability to obtain breast fluid: 1) age up to 35 to 50 years; 2) earlier age at menarche; 3) non-Asian compared to Asian ethnicity; and 4) history of lactation. Exogenous estrogen use, endogenous estrogen concentrations, phase of menstrual cycle, family history of breast cancer, type of menopause, and less than full-term pregnancy consistently did not influence ability to obtain fluid. New findings from this study shed light on some apparently contradictory findings from the previous studies. In particular, this study showed that the effects of age on ability to obtain fluid appeared to be independent of the effects of menopause. Furthermore, discrepancies in previous findings on the effects of parity on ability to obtain fluid may be explained by our finding that the increased ability to obtain fluid from parous compared to nulliparous women applied only to parous women who had breastfed.

Adult↗
PubMed1979

Flow cytometry of human gynecologic specimens using log chromomycin A3 fluorescence and log 90 degrees light scatter.

Flow cytometry and electronic cell sorting are being investigated to screen gynecologic specimens for cervical neoplasia. Cellular DNA content is quantitated by Chromomycin A3 fluorescence and cell size is quantitated by 90 degrees light scatter; the logarithms of the measured intensities are used to produce a two parameter histogram. To determine the cell types responsible for signals in various histogram regions, systematic electronic cell sorting is performed. The sorted fractions are sedimented into microscope slides and stained by the Papanicolaou technique. The cells in each fraction are identified by conventional cytomorphologic criteria. Morphologic analysis of sorted cells reveals histogram regions corresponding to specific cell types. One very important region contains the highest concentration of signals from abnormal cells and is therefore the best region to analyze for specimen abnormality. However, because a significant number of signals in this region are from normal cells, specimens cannot be diagnosed by their analysis. Another important histogram region is composed primarily of signals from endocervical columnar and metaplastic cells. The presence of such cells is a good criterion for specimen adequacy, therefore analysis of signals in this region is essential to assess specimen adequacy for automatic screening.

Cervix Uteri↗
PubMed1977

A cytomorphologic approach to standardization of cell dispersal evaluation for gynecologic specimens.

Dispersal of cells in gynecologic specimens is a major concern in sample preparation for automated systems. A variety of dispersal techniques has been tested, with varying degrees of success reported by many laboratories. In order to have a more meaningful comparison of the results of different techniques and among investigators, a standardized evaluation procedure is desirable. The cytomorphologic element of evaluation of cell dispersal has been developed and tested in this laboratory and might be applied toward this purpose. This evaluation reveals the changes in relative numbers of single cells according to cell type and estimates cell loss as well as changes in cellular preservation. Groups of cells are tabulated according to whether they appear as definite tissue groups or as clumps of single cells. Because abnormal cells and cells from the transformation zone often occur in tissue groups, special emphasis is placed on dispersal analysis by cell type to reveal whether the diagnostically important cells and cells relating to specimen adequacy were optimally dispersed. Furthermore, the format of evaluation allows assessment of the applicability of dispersal procedures to preparation for both flow and slide-based systems of automated cytology.

Autoanalysis↗
PubMed1975

Chlamydial infection in women with cervical dysplasia.

The prevalence of antibodies to chlamydiae, particularly to TRIC (trachoma-inclusion conjunctivitis) agents, was studied in women with cervical dysplasia and in women attending selected clinics (obstetrics, cancer-screening, and gynecology). In addition, attempts were made to isolate TRIC agents and herpesviruses from the cervices of these women. TRIC agent recovery rates 4.1 per cent for women with dysplasia, 5.4 per cent for pregnant women, 7.8 per cent in the women's clinic, and 0.8 per cent in the cancer-screening clinic. Herpesvirus recovery rates were lower, on the order of 1 per cent or less in each clinic. Complement-fixing antibodies to chlamydial group antigen were detected in 21.5 per cent of women with dysplasia. With a more sensitive fluorescent antibody method, 77.6 per cent of the women with dysplasia or cervical cancer were shown to have antibodies to chlamydiae. In general, antichlamydial antibodies were less prevalent in the other clinic populations. The results of this study indicate that women with cervical dysplasia or cancer may have a high prevalence of antibodies to sexually transmitted agents other than herpesvirus type 2.

Adolescent↗
PubMed1975

Cellular composition of the nipple aspirate specimen of breast fluid. I. The benign cells.

A nipple aspirator device was used to obtain breast secretions for cytologic examination, as well as for viral and biochemical analysis. Examination of the first 1,456 specimens from 796 women revealed ductal epithelium in 54%. Ductal epithelial cells were often absent in specimens from normal women; however, 78.5% of women with benign breast disease on tissue biopsy had specimens containing ductal epithelium. Apocrine metaplastic cells were a further indication of the presence of breast disease, and were rarely found in specimens from asymptomatic women. Foam cells were often abundant in specimens from normal breasts, but were found in decreased numbers in specimens from women benign breast disease. Differences in the occurrence of ductal epithelial cells, apocrine metaplastic cells, and foam cells suggest an alteration in the rate of maturation of ductal epithelium in women with both benign and malignant breast disease. The finding of a relative abundance of cells in nipple aspirate specimens from women with breast disease and few or no cells in specimens from women with normal breasts is believed to be of great importance in the cytologic evaluation of nipple aspirate specimens.

Body Fluids↗
PubMed1975

Cellular composition of the nipple aspirate specimen of breast fluid. II. Abnormal findings.

Studies of cellular findings in nipple aspirate specimens from 796 women revealed 50 women with abnormal cells and/or microcalcifications. The clinical correlation of these abnormalities with breast cancer appears to be highly significant: abnormal cells were found in 50% of the satisfactory specimens from women who had breast cancer or who had had a previous mastectomy for breast cancer. Continued observation of the women for evidence of regression, persistence, or progression of the cytologic abnormalities is required to determine the significance of the abnormalities. Microcalcifications were present in nipple aspirates from 27% of the women whose mammograms were interpreted as showing calcification. The absence of mammographic confirmation of the cytologic findings of microcalcifications may be an indication for re-evaluation of the existing mammograms and repeat clinical and mammographic examination at more frequent intervals for early localization of small lesions.

Adult↗
PubMedDate not supplied

Comparison of cellular recovery rates and morphologic detail obtained using membrane filter and cytocentrifuge techniques.

Two methods commonly used for collecting cells from a large volume of fluid-membrane filters (Millipore, Gelman, and Nuclepore) and cytocentrifugation-were compared for percentage of cell recovery and degree of cell preservation. Twenty samples of body cavity fluid were centrifuged, and the buffy coat of each was resuspended in a balanced electrolyte solution. The cellularity of each suspension was determined using both Coulter Counter and hemocytometer. Exact aliquots of each sample were collected on Millipore, Gelman, and Nuclepore filters and on slides by cytocentrifugation (Shandon). The resultant material was fixed in alcohol (95% ethanol), stained by the Papanicolaou method, mounted, and then evaluated with respect to the number of cells present and the diagnostically significant morphologic detail of the cells. Cell recovery was estimated by counting cells in known areas of each preparation and then ascertaining the total area. The Millipore filter technique consistently recovered the highest percentage of cells and preserved the best morphologic detail.

Body Fluids↗
PubMedDate not supplied

Cerebrospinal fluid cytology: diagnostic accuracy and comparison of different techniques.

Cytologic examination of cerebrospinal fluid was performed in 1,021 patients, using Nuclepore and Millipore filter techniques. Positive findings were obtained in 89 cases, including 40 with primary central nervous system tumors, 24 with metastatic tumors and 25 with leukemic or lymphomatous involvement. When correlated with histologic findings, the overall detection rate was 32.2 per cent for primary tumors, 53.3 per cent for metastatic tumors and 65.8 per cent for leukemia and lymphoma. Highest degree of accuracy in the primary tumor group was achieved with medulloblastoma (61.9 per cent). Among metastatic tumors, those originating in the lung (70 per cent) and breast (83 per cent) were the one most often detected. Comparison of the two filter techniques indicated a slightly higher detection rate when the Millipore filter was used. The reasons for this are not entirely clear, but increased cellular yield with the Millipore filter may be an important factor. The cytocentrifuge method was found to be generally inferior to either of the filter techniques in quality of cell preservation. Our findings indicate that diagnostic usefulness of cerebrospinal cytology depends on collection and preparation methods as well as the anatomic distribution and biologic behavior of the lesions.

Cerebrospinal Fluid↗
PubMedDate not supplied

Adenocarcinoma with a neuroendocrine component arising in the urachus. A case report.

The clinical, cytologic, histologic and ultrastructural findings in a mixed adenocarcinoma and neuroendocrine carcinoma of the urinary bladder urachus, an extremely rare tumor only recently described, are presented for a 31-year-old woman who died of widespread metastatic disease six months following the initial diagnosis and treatment. Cytologic study of voided urine and bladder washings disclosed the presence of malignant cells with the features of a small cell carcinoma; retrospectively, scarce adenocarcinoma cells were also identified in those specimens. Histologic study of resection specimens, including the use of special stains and electron microscopy, confirmed the presence of a small cell component, consistent with the poor prognosis in this case. Image analysis measurements of the malignant cells suggested a high proliferation rate.

Adenocarcinoma↗
PubMedDate not supplied

Cerebrospinal fluid cytomorphology identification of benign cells originating in the central nervous system.

The chief cellular consituents of CSF are the "free cells" of the pia-arachnoid, ependyma, and choroid. These cells are of diverse types, but have their mesenchymal origin in common. Usually they offer no difficulty in identification since they are predominantly histiocytic. However, these "free cells" may be morphologically changed in reaction to an appropriate stimulus, and may therefore be a source of error in diagnostic material. Cells having mesothelial characteristics are not found in the CSF compartment and therefore the term pia-arachnoid mesothelial cells appears inappropriate. The only neuroectodermal derivative that was easily identifiable was the choroidal cell. It is distinctive and unequivocal. We were unable to recognize ependymal cells in our present study. Glial cells (protoplasmic and fibrous astrocytes) and neurons can be recognized when neural tissue is penetrated in the process of collecting CSF.

Animals↗
PubMedDate not supplied

The incidence and significance of intracytoplasmic calcifications in nipple aspirate specimens.

Intracytoplasmic deposits demonstrated to be calcifications have been identified in nipple aspirates from 3.6 per cent of breasts with satisfactory cytology. The deposits occurred almost exclusively in epithelial groups, and their structure ranged from dust-like particles and spiculated forms to psammoma bodies; all exhibited characteristic density, refractility and well-defined, irregular borders. Nipple aspirates containing calcifications were typically characterized by the presence of numerous epithelial groups, frequently of papillary type. This association was supported histologically by the fact that 11 of the 14 available tissue specimens contained papillary lesions in the duct system, including three with papillary carcinoma in situ. Cytologic abnormality was significantly associated with the presence of calcifications, and marked cellular changes were found four times as often in this group as in the total population with satisfactory cytology. Calcific deposits were found in six of the fourteen available tissue specimens, four of which contained breast carcinoma. Calcifications were noted in only 23 per cent of 97 available mammograms, but further investigation has revealed other significant radiologic findings. Cytologic calcifications were found most frequently in aspirates from women between the ages of 41 and 60 and were often associated with clinical findings of breast disease. Preliminary findings indicate an increased prevalence of breast carcinoma in patients with cytologic calcifications and suggest that such patients may require closer than normal follow-up.

Adult↗
PubMedDate not supplied

Application of electron microscopy in the definitive diagnosis of effusions.

Electron microscopy was performed on a series of body cavity fluid specimens to evaluate the usefulness of this technique in the diagnosis of effusions. During a six-month period, 42 specimens were examined, 19 benign and 23 malignant. In two cases, the electron microscopic findings were crucial to the diagnosis. In a third case, electron microscopy helped to confirm the diagnosis and avoid unnecessary surgery. In a number of other cases, ultrastructural evaluation demonstrated special cell characteristics not evident in routine light microscopic studies. Based on these findings, we conclude that electron microscopy has a definite place in the diagnosis of effusions and should be increasingly utilized on a selective basis in the evaluation of body cavity fluid specimens. In addition, electron microscopic studies on cells in effusions provide an excellent source of material for educational and research purposes.

Adenocarcinoma↗
PubMedDate not supplied

Plasminogen activator as a diagnostic marker for preneoplastic cells in human gynecologic specimens.

A modified fibrin-agar overlay assay was used to measure the fibrinolytic activity in human cervical epithelial cells. The fibrinolytic activity results from a cell-associated serine protease that acts as a plasminogen activator. An enzymatic and morphologic comparison of individual normal and abnormal cells reveals that about 50% of the dysplastic and carcinoma in situ cells contain high levels of the activator. Forty percent of morphologically normal metaplastic cells also exhibit high activities of plasminogen. Forty percent of morphologically normal metaplastic cells also exhibit high activities of plasminogen activator. Most normal intermediate and superficial epithelial cells and all erythrocytes and leukocytes are inactive. The frequency of plasminogen activator-containing cells was somewhat higher in cytomorphologically abnormal samples than in normal samples.

Carcinoma in Situ↗