Samuel J. Agronow

Genital warts and cervical cancer

Human papillomaviral infection is now widely implicated in the causation of cervical neoplasia. Genotype analysis provides the best guide to biologic outcome; most polyploid lesions regress and most aneuploid ones persist or progress. This prospective survey examined the relationships between cell ploidy and 24 objectively validated criteria of human papillomaviral infection or premalignant change in 52 biopsies from a dysplasia clinic. Histologic evidence of benign warty expression and human papillomaviral capsid antigen production decreased steadily as DNA content ranged from diploidy to polyploidy to aneuploidy. In contrast, premalignant change increased with progressive distortion of nuclear DNA content. No absolute discriminants were found between polyploidy and aneuploidy, as evidenced by the detection of human papillomaviral proteins in three of 21 aneuploid epithelia and the recognition of abnormal mitotic figures in five of 17 polyploid lesions. Polyploid and aneuploid lesions differed only in severity, and it appears that some polyploid epithelia may be transition forms between diploidy and aneuploidy.

Genital warts and cervical cancer: IV. A colposcopic index for differentiating subclinical papillomaviral infection from cervical intraepithelial neoplasia☆

Five colposcopic signs (thickness, color, contour, vascular atypia, and iodine staining) were graded into three objective categories representing (1) subclinical papillomaviral infection, (2) lower-grade dysplasia, and (3) grade 3 cervical intraepithelial neoplasia. Seventy-two colposcopically different biopsy specimens (25 of subclinical papillomaviral infection and 18 of grade 1, 18 of grade 2, and 11 of grade 3 cervical intraepithelial neoplasia) were collected from 52 women and interpreted by validated, quantitative histologic analysis. Attempts to grade lesions by the prominence of the acetowhitening reaction or the mere presence of aberrant surface capillaries were unsuccessful. In contrast, each of five new colposcopic criteria were significantly correlated with histologic severity. Differences in color, vascular atypia, and iodine staining were more predictive than those of thickness and contour. Combined into a weighted index, these colposcopic features were 96% correct in forecasting approximate histologic findings. Because this method relies upon critical analysis rather than pattern recall, the use of this colposcopic index greatly simplifies the learning of colposcopy.

Genital warts and cervical cancer. III. Subclinical papillomaviral infection and cervical neoplasia are linked by a spectrum of continuous morphologic and biologic change

Human papillomaviral (HPV) infection is now widely advanced as an important etiologic factor in cervical cancer. This study was undertaken to clarify morphologic relationships within the biologic spectrum linking subclinical papillomaviral infection (SPI) to cervical intraepithelial (CIN). Two pathologists analyzed 72 colposcopic biopsies, using a semi‐objective rating scheme that scored 24 different histologic criteria. Each individual criterion was checked for reproducibility, and validated against an objective measure of papillomaviral infection (immunoperoxidase staining) or premalignant change (microspec‐trophotometry). The individual criteria were then combined into histologic indices of benign warty change, presumed viral atypia, abnormal cell phenotype, and disturbed tissue maturation. Histologic expression of papillomaviral infection decreased with increasing degrees of premalignant change. Plotting the index of abnormal cell phenotype against that of disturbed tissue maturation produced a linear plot in which cases clustered into four diagnostic groups. The histologic indices of papillomaviral infection displayed significant curvilinear correlations with genotypic distortion, benign warty change being maximal in the CIN 1 range and presumed viral atypia in the CIN 2 range. Disturbance of nuclear DNA content also increased with worsening diagnosis; diploidy being most common in SPI (67%), polyploidy in CIN 1 (59%), and aneuploidy in CIN 2 (65%) and CIN 3 (82%). Conversely, capsid antigen production decreased from 36% in SPI to 9% in CIN 3. Three aneuploid epithelia were immunoperoxidase positive. These inverse relationships between late viral expression and nuclear distortion fit experimental models of viral oncogenesis. The gradual transition and morphologic overlap between diagnostic groups support the postulate that SPI and CIN are a single disease spectrum, in which differences are those of degree rather than of kind.

In vitro sperm cervical mucus penetration: studies in human and bovine cervical mucus

The objective of this study was to assess the feasibility of substituting bovine estrus cervical mucus (BCM) for human midcycle cervical mucus (MCM) for investigation of sperm cervical mucus (CM) interaction and evaluation of cervical factor in infertility. In vitro sperm cervical mucus penetration tests (ICMPT) were performed with the use of ejaculated human spermatozoa collected from fertile donors and infertile men. Tests were performed in a flat capillary tube with the use of MCM and BCM. Mean +/- standard deviation (SD) of sperm penetration in MCM was 32.3 +/- 15.5 mm and in BCM 27.3 +/- 12.1 mm after 90 minutes of migration. The difference was significant (P less than 0.001). A highly significant correlation was found between sperm penetration in MCM and BCM. The depth of sperm penetration in both human cervical mucus (HCM) and BCM was also significantly related to sperm count and motility. Positive correlation was observed between normal morphologic features and sperm migration in BCM but not in MCM. It is concluded that human sperm penetrate BCM at a slower rate than MCM, but BCM can be effectively substituted for HCM in laboratory testing of sperm penetration.

Genital warts and cervical cancer: V. The tissue basis of colposcopic change

Histologic differences between subclinical papillomaviral infection and cervical intraepithelial neoplasia are quantitative rather than qualitative. Both entities are characterized colposcopically by acetowhite epithelium and aberrant surface capillaries. This study correlates five new colposcopic signs (variations in contour, thickness, color, vascular patterns, and iodine staining) with 12 histologic signs of human papillomaviral infection and 12 features of premalignant change. Acetowhitening and capillary abnormalities in minor colposcopic lesions are attributable to human papillomaviral disturbance of cell growth and maturation, seen histologically as parabasal layer proliferation, papillomatosis, koilocytosis , and dyskeratosis. Alteration in cell ploidy is usually minimal. Major colposcopic abnormalities reflect extensive disorganization of cell phenotype and tissue architecture, increased DNA content, and aneuploid stem cell populations. Intermediate colposcopic patterns generally denote polyploid lesions in which tissue changes are a composite of two reciprocal events: the extent of benign warty expression and the severity of premalignant change.

Affective behavior of abused and control children: comparisons of parent-child interactions and the influence of home environment variables.

Affective behaviors of 14 pairs of infant and preschool abused and control children matched on age, race, sex, and socioeconomic level were assessed in parent-child interaction. Subgroups of abused and control samples were formed by introduction of selected home environment variables chosen to represent properties of the parent-child dyad. Matched-pairs analysis showed few matched t-test comparisons to be significant. However, significant interactions were observed when two-way analyses of variance were performed with abused-control and status of home environment as factors. For positive affective behaviors, the abused group favored on home environment variables was higher than the favored control group. For negative affective behaviors, the abused group less-favored on home environment variables was higher than the less-favored control group. As a response to abuse, an increased sensitivity to the physical and social stimulation of the home environment is proposed.

Affective Investments of Preschool Children: Positive Responsivity

Summary Affective investments of 27 preschool children were observed in three task situations. An observational checklist assessed the presence or absence in 30-second segments of 55 behaviors taken to be indicative of 11 dimensions of positive affective tone. Each child was scored separately in each situation through repetitive viewings of video tapes. With increasing age, affective expression was found to increase in incidence, duration, and appropriateness to task demands. The observational checklist was examined for reliability and validity. Factor analysis provided three independent factors which summarized the 11 dimensions of affective tone: (a) open and interactive with the environment, (b) expressive towards other versus self-absorbed comfort-seeking, and (c) initiative.

Maintenance of a Genetic Data Set on Multiple Data Base and Statistical Analysis Systems

A data base centered on chromosome analysis of amniotic cells is maintained on multiple data base management and statistical analysis systems. The data are collected from patients referred for karyotyping and genetic counseling either to the Wayne State University’s C. S. Mott Center or Detroit’s Hutzel Hospital. Data include primary and secondary McKusick and Birth Defects diagnoses, alpha-feto protein values, karyotypes, medical data from patient charts - e.g., pedigree, parity, gravidity, gestational age, past medical problems, demographic variables, such as age, address, phone, referral source, and follow-up information. The powerful interactive capabilities of the Michigan Terminal System (MTS) (l), the major operating system on Wayne State University’s Amdahl 470V/6 computer, are used for initial data entry. With the aid