Inter-cellular forces orchestrate contact inhibition of locomotion.

Contact inhibition of locomotion (CIL) is a multifaceted process that causes many cell types to repel each other upon collision. During development, this seemingly uncoordinated reaction is a critical driver of cellular dispersion within embryonic tissues. Here, we show that Drosophila hemocytes require a precisely orchestrated CIL response for their developmental dispersal. Hemocyte collision and subsequent repulsion involves a stereotyped sequence of kinematic stages that are modulated by global changes in cytoskeletal dynamics. Tracking actin retrograde flow within hemocytes in vivo reveals synchronous reorganization of colliding actin networks through engagement of an inter-cellular adhesion. This inter-cellular actin-clutch leads to a subsequent build-up in lamellar tension, triggering the development of a transient stress fiber, which orchestrates cellular repulsion. Our findings reveal that the physical coupling of the flowing actin networks during CIL acts as a mechanotransducer, allowing cells to haptically sense each other and coordinate their behaviors.

Emergence of embryonic pattern through contact inhibition of locomotion.

The pioneering cell biologist Michael Abercrombie first described the process of contact inhibition of locomotion more than 50 years ago when migrating fibroblasts were observed to rapidly change direction and migrate away upon collision. Since then, we have gleaned little understanding of how contact inhibition is regulated and only lately observed its occurrence in vivo. We recently revealed that Drosophila macrophages (haemocytes) require contact inhibition for their uniform embryonic dispersal. Here, to investigate the role that contact inhibition plays in the patterning of haemocyte movements, we have mathematically analysed and simulated their contact repulsion dynamics. Our data reveal that the final pattern of haemocyte distribution, and the details and timing of its formation, can be explained by contact inhibition dynamics within the geometry of the Drosophila embryo. This has implications for morphogenesis in general as it suggests that patterns can emerge, irrespective of external cues, when cells interact through simple rules of contact repulsion.

Laparoscopic optical coherence tomography imaging of human ovarian cancer.

OBJECTIVES: Ovarian cancer is the fourth leading cause of cancer-related death among women in the US largely due to late detection secondary to unreliable symptomology and screening tools without adequate resolution. Optical coherence tomography (OCT) is a recently emerging imaging modality with promise in ovarian cancer diagnostics, providing non-destructive subsurface imaging at imaging depths up to 2 mm with near-histological grade resolution (10-20 microm). In this study, we developed the first ever laparoscopic OCT (LOCT) device, evaluated the safety and feasibility of LOCT, and characterized the microstructural features of human ovaries in vivo. METHODS: A custom LOCT device was fabricated specifically for laparoscopic imaging of the ovaries in patients undergoing oophorectomy. OCT images were compared with histopathology to identify preliminary architectural imaging features of normal and pathologic ovarian tissue. RESULTS: Thirty ovaries in 17 primarily peri- or post-menopausal women were successfully imaged with LOCT: 16 normal, 5 endometriosis, 3 serous cystadenoma, and 4 adenocarcinoma. Preliminary imaging features developed for each category reveal qualitative differences in the homogeneous character of normal post-menopausal ovary, the ability to image small subsurface inclusion cysts, and distinguishable features for endometriosis, cystadenoma, and adenocarcinoma. CONCLUSIONS: We present the development and successful implementation of the first laparoscopic OCT probe. Comparison of OCT images and corresponding histopathology allowed for the description of preliminary microstructural features for normal ovary, endometriosis, and benign and malignant surface epithelial neoplasms. These results support the potential of OCT both as a diagnostic tool and an imaging modality for further evaluation of ovarian cancer pathogenesis.

Complete resolution of Paget disease of the vulva with imiquimod cream.

Extra mammary Paget disease (EMPD) is a neoplastic disease of apocrine gland bearing skin. Surgical excision is the standard of care for EMPD; however, it is accompanied by recurrence in more than 60% of the patients. Recently, imiquimod cream has been reported to induce complete responses in primary or recurrent EMPD. We report on 2 women with vulva EMPD who achieved biopsy-confirmed resolution of their disease after topical application of imiquimod 5% cream.

Apical and Basal Matrix Remodeling Control Epithelial Morphogenesis.

Epithelial tissues can elongate in two dimensions by polarized cell intercalation, oriented cell division, or cell shape change, owing to local or global actomyosin contractile forces acting in the plane of the tissue. In addition, epithelia can undergo morphogenetic change in three dimensions. We show that elongation of the wings and legs of Drosophila involves a columnar-to-cuboidal cell shape change that reduces cell height and expands cell width. Remodeling of the apical extracellular matrix by the Stubble protease and basal matrix by MMP1/2 proteases induces wing and leg elongation. Matrix remodeling does not occur in the haltere, a limb that fails to elongate. Limb elongation is made anisotropic by planar polarized Myosin-II, which drives convergent extension along the proximal-distal axis. Subsequently, Myosin-II relocalizes to lateral membranes to accelerate columnar-to-cuboidal transition and isotropic tissue expansion. Thus, matrix remodeling induces dynamic changes in actomyosin contractility to drive epithelial morphogenesis in three dimensions.

Disparities in the Management of Patients With Stage I Small Cell Lung Carcinoma (SCLC): A Surveillance, Epidemiology and End Results (SEER) Analysis.

INTRODUCTION: Patients with stage I small cell lung carcinoma (SCLC) are candidates for surgery; however, not much is known regarding the utilization of surgical resection in the management of stage I SCLC and the factors that determine the patient's ability to receive surgery. METHODS: The Surveillance, Epidemiology and End Results database was used to identify patients with stage I SCLC from 2007 to 2013. Continuous variables were compared with 1-way analysis of variance, and categorical variables were compared with χ2 testing. Multivariable logistic regression analyses were used to obtain odds ratios. RESULTS: Of the 1902 patients with stage I SCLC, 427 (22.4%) underwent resection, 116 (6.1%) resection and radiation, 815 (42.8%) received radiation alone, and 544 (28.6%) did not undergo surgery or radiation. Median overall survival for patients with surgery plus radiation was 60+ months, followed by surgery alone at 50 months, radiation at 27 months, and no resection/radiation 16 months. Patients with ≥ 4 lymph nodes removed during surgery had better overall survival of 60+ months compared with patients with < 4 lymph nodes removed (25 months); P < .001. Multivariate analysis demonstrated that elderly patients, men, African American individuals, Medicaid recipients, and patients with left-sided tumors were less likely to undergo resection. However, county-level socioeconomic factors, such as level of poverty, education, unemployment, and median income did not affect the likelihood of undergoing resection. CONCLUSIONS: Fewer than one-third of all patients with stage I SCLC undergo resection despite better outcomes with resection. Elderly African American men with Medicaid insurance were less likely to receive resection.

Eye-movement study and human performance using telepathology virtual slides: implications for medical education and differences with experience.

A core skill in diagnostic pathology is light microscopy. Remarkably little is known about human factors that affect the proficiency of pathologists as light microscopists. The cognitive skills of pathologists have received relatively little attention in comparison with the large literature on human performance studies in radiology. One reason for this lack of formal visual search studies in pathology has been the physical restrictions imposed by the close positioning of a microscope operator's head to the microscope's eyepieces. This blocks access to the operator's eyes and precludes assessment of the microscopist's eye movements. Virtual slide microscopy now removes this barrier and opens the door for studies on human factors and visual search strategies in light microscopy. The aim of this study was to assess eye movements of medical students, pathology residents, and practicing pathologists examining virtual slides on a digital display monitor. Whole histopathology glass slide digital images, so-called virtual slides, of 20 consecutive breast core biopsy cases were used in a retrospective study. These high-quality virtual slides were produced with an array-microscope equipped DMetrix DX-40 ultrarapid virtual slide processor (DMetrix, Tucson, Ariz). Using an eye-tracking device, we demonstrated for the first time that when a virtual slide reader initially looks at a virtual slide his or her eyes are very quickly attracted to regions of interest (ROIs) within the slide and that these ROIs are likely to contain diagnostic information. In a matter of seconds, critical decisions are made on the selection of ROIs for further examination at higher magnification. We recorded: (1) the time virtual slide readers spent fixating on self-selected locations on the video monitor; (2) the characteristics of the ways the eyes jumped between fixation locations; and (3) x and y coordinates for each virtual slide marking the sites the virtual slide readers manually selected for zooming to higher ROI magnifications. We correlated the locations of the visually selected fixation locations and the manually selected ROIs. Viewing profiles were identified for each group. Fully trained pathologists spent significantly less time (mean, 4.471 seconds) scanning virtual slides when compared to pathology residents (mean, 7.148 seconds) or medical students (mean, 11.861 seconds), but had relatively prolonged saccadic eye movements (P < .0001). Saccadic eye movements are defined as eye movements between fixation locations. On the other hand, the pathologists spent significantly more time than trainees dwelling on the 3 locations they subsequently chose for zooming. Unlike either the medical students or the residents, the pathologists frequently choose areas for viewing at higher magnification outside of areas of foveal (central) vision. Eye movement studies of scanning pathways (scan paths) may be useful for developing eye movement profiles for individuals and for understanding the difference in performances between novices and experts. They may also be useful for developing new visual search strategies for rendering diagnoses on telepathology virtual slides.

An array microscope for ultrarapid virtual slide processing and telepathology. Design, fabrication, and validation study.

This paper describes the design and fabrication of a novel array microscope for the first ultrarapid virtual slide processor (DMetrix DX-40 digital slide scanner). The array microscope optics consists of a stack of three 80-element 10 x 8-lenslet arrays, constituting a "lenslet array ensemble." The lenslet array ensemble is positioned over a glass slide. Uniquely shaped lenses in each of the lenslet arrays, arranged perpendicular to the glass slide constitute a single "miniaturized microscope." A high-pixel-density image sensor is attached to the top of the lenslet array ensemble. In operation, the lenslet array ensemble is transported by a motorized mechanism relative to the long axis of a glass slide. Each of the 80 miniaturized microscopes has a lateral field of view of 250 microns. The microscopes of each row of the array are offset from the microscopes in other rows. Scanning a glass slide with the array microscope produces seamless two-dimensional image data of the entire slide, that is, a virtual slide. The optical system has a numerical aperture of N.A.= 0.65, scans slides at a rate of 3 mm per second, and accrues up to 3,000 images per second from each of the 80 miniaturized microscopes. In the ultrarapid virtual slide processing cycle, the time for image acquisition takes 58 seconds for a 2.25 cm2 tissue section. An automatic slide loader enables the scanner to process up to 40 slides per hour without operator intervention. Slide scanning and image processing are done concurrently so that post-scan processing is eliminated. A virtual slide can be viewed over the Internet immediately after the scanning is complete. A validation study compared the diagnostic accuracy of pathologist case readers using array microscopy (with images viewed as virtual slides) and conventional light microscopy. Four senior pathologists diagnosed 30 breast surgical pathology cases each using both imaging modes, but on separate occasions. Of 120 case reads by array microscopy, there were 3 incorrect diagnoses, all of which were made on difficult cases with equivocal diagnoses by light microscopy. There was a strong correlation between array microscopy vs. "truth" diagnoses based on surgical pathology reports. The kappa statistic for the array microscopy vs. truth was 0.96, which is highly significant (z=10.33, p <0.001). There was no statistically significant difference between rates of agreement with truth between array microscopy and light microscopy (z=0.134, p >0.05). Array microscopy and light microscopy did not differ significantly with respect to the number/percent of correct decisions rendered (t=0.552, p=0.6376) or equivocal decisions rendered (t=2.449, p=0.0917). Pathologists rated 95.8% of array microscopy virtual slide images as good or excellent. None were rated as poor. The mean viewing time for a DMetrix virtual slide was 1.16 minutes. The DMetrix virtual slide processor has been found to reduce the virtual slide processing cycle more than 10 fold, as compared with other virtual slide systems reported to date. The virtual slide images are of high quality and suitable for diagnostic pathology, second opinions, expert opinions, clinical trials, education, and research.

Imaging of the ovary.

Epithelial ovarian cancer has the highest mortality rate among the gynecologic cancers and spreads beyond the ovary in 90% of the women diagnosed with ovarian cancer. Detection before the disease has spread beyond the ovary would significantly improve the survival from ovarian cancer, which is currently only 30% over 5 years, despite extensive efforts to improve the survival. This study describes initial investigation of the use of optical technologies to improve the outcome for this disease by detecting cancers at an earlier and more treatable stage. Women undergoing oophorectomy were recruited for this study. Ovaries were harvested for fluorescence spectroscopy, confocal microscopy, and optical coherence tomography. Fluorescence spectroscopy showed large diagnostic differences between normal and abnormal tissue at 270 and 340 nm excitation. Optical coherence tomography was able to image up to 2mm deep into the ovary with particular patterns of backscattered intensity observed in normal versus abnormal tissue. Fluorescence confocal microscopy was able to visualize sub-cellular structures of the surface epithelium and underlying cell layers. Optical imaging and/or spectroscopy has the potential to improve the diagnostic capability in the ovary, but extended systematic investigations are needed to identify the unique signatures of disease. The combination of optical technologies supported by modern molecular biology may lead to an instrument that can accurately detect early carcinogenesis.

Tailored endovascular repair of traumatic aortic disruptions with "stacked" abdominal aortic extension cuffs.

OBJECTIVE: The management paradigm for traumatic aortic disruptions has evolved from open to endovascular repair. Thoracic stent grafts designed to treat aneurysmal disease, however, have disadvantages, including size mismatch in younger trauma patients and current standard lengths, which may needlessly necessitate coverage of at least 10 cm of thoracic aorta, increasing the risk of spinal cord ischemia. The "off-label" use of abdominal aortic extension cuffs to treat traumatic aortic disruptions may provide an advantage in this regard by better size matching for the younger trauma patient, reduced thoracic aortic coverage, and less cost to the institution. METHODS: From 2008 to 2011, a total of 16 traumatic aortic disruptions were evaluated and managed with endovascular techniques. The last six were treated with abdominal aortic extensions cuffs (Excluder Extension Cuffs; W.L. Gore & Associates, Flagstaff, AZ) rather than traditional thoracic stent grafts. In addition to demographics and trauma-related data, additional endpoints evaluated in this retrospective review included operative time, number of cuffs used, stent cost data, procedural complications, and follow-up. RESULTS: All six patients (five men/one woman) with traumatic aortic disruption were successfully treated with complete exclusion of the disruption using abdominal aortic cuffs. There were no complications including death or spinal cord ischemia. The average age was 27 years (range, 18-44 years). The average number of cuffs used to cover the traumatic tear was 2.6 per patient (range, 2-3 cuffs per patient), covering an average of 5.3 cm of thoracic aorta (range, 4-6 cm). Mean procedure time was 70 minutes. Hospital cost for each cuff was $2200 (average total stent cost per patient, $5720). For comparison, a single 10-cm conformable thoracic aortic graft (CTAG) (Gore) costs $14,500. Average follow-up of all six patients for up to 3 years demonstrates no complications or migration of the stent grafts. CONCLUSIONS: Traumatic aortic disruptions can be safely and selectively managed with "stacked" abdominal aortic extension cuffs. This tailored therapy may provide advantages over traditional thoracic stents, including improved size match in a younger trauma patient, less aortic coverage, and reduced cost.

Analysis of second-harmonic-generation microscopy in a mouse model of ovarian carcinoma.

Second-harmonic-generation (SHG) imaging of mouse ovaries ex vivo was used to detect collagen structure changes accompanying ovarian cancer development. Dosing with 4-vinylcyclohexene diepoxide and 7,12-dimethylbenz[a]anthracene resulted in histologically confirmed cases of normal, benign abnormality, dysplasia, and carcinoma. Parameters for each SHG image were calculated using the Fourier transform matrix and gray-level co-occurrence matrix (GLCM). Cancer versus normal and cancer versus all other diagnoses showed the greatest separation using the parameters derived from power in the highest-frequency region and GLCM energy. Mixed effects models showed that these parameters were significantly different between cancer and normal (P<0.008). Images were classified with a support vector machine, using 25% of the data for training and 75% for testing. Utilizing all images with signal greater than the noise level, cancer versus not-cancer specimens were classified with 81.2% sensitivity and 80.0% specificity, and cancer versus normal specimens were classified with 77.8% sensitivity and 79.3% specificity. Utilizing only images with greater than of 75% of the field of view containing signal improved sensitivity and specificity for cancer versus normal to 81.5% and 81.1%. These results suggest that using SHG to visualize collagen structure in ovaries could help with early cancer detection.

7,12-dimethylbenz[a]anthracene induces sertoli-leydig-cell tumors in the follicle-depleted ovaries of mice treated with 4-vinylcyclohexene diepoxide.

Ovarian cancer is associated with high mortality due to its late onset of symptoms and lack of reliable screening methods for early detection. Furthermore, the incidence of ovarian cancer is higher in postmenopausal women. Mice rendered follicle-depleted through treatment with 4-vinylcyclohexene diepoxide (VCD) are a model of ovary-intact menopause. The present study was designed to induce ovarian neoplasia in this model by treating mice with 7,12-dimethylbenz[a]anthracene (DMBA). Female B6C3F1 mice (age, 28 d) received intraperitoneal sesame oil (vehicle; VCD- groups) as a control or VCD (160 mg/kg; VCD+ groups) daily for 20 d to cause ovarian failure. Four months after the onset of dosing, mice from each group received a single injection of DMBA (VCD-DMBA+ and VCD+DMBA+ groups, n = 15 per group) or vehicle control (VCD-DMBA-, n = 15; VCD+ DMBA-, n = 14) under the bursa of the right ovary. Ovaries were collected 3 or 5 mo after injection and processed for histologic evaluation. Immunohistochemistry was used to confirm classification of neoplasms. None of the animals in the VCD-DMBA- and VCD-DMBA+ groups (that is, mice still undergoing estrus) had tumors at either time point. At the 3-mo time point, 12.5% of the VCD+DMBA+ mice had ovarian tumors; at 5 mo, 57.1% of the VCD+DMBA+ and 14.3% of VCD+DMBA- ovaries had neoplasms. Neoplasms stained positively for inhibin alpha (granulosa cells) and negatively for keratin 7 (surface epithelium), thus confirming classification of the lesions as Sertoli-Leydig cell tumors. These findings provide evidence for an increased incidence of DMBA-induced ovarian neoplasms in the ovaries of follicle-depleted mice compared with that in age-matched cycling controls.

Simultaneous optical coherence tomography and laser induced fluorescence imaging in rat model of ovarian carcinogenesis.

Determining if an ovarian mass is benign or malignant is an ongoing clinical challenge. The development of reliable animal models provides means to evaluate new diagnostic tools to more accurately determine if an ovary has benign or malignant features. Although sex cord-stromal tumors (SCST) account for 0.1­0.5% of ovarian malignancies, they have similar appearances to more aggressive epithelial cancers and can serve as a prototype for developing better diagnostic methods for ovarian cancer. Optical coherence tomography (OCT) and laser-induced fluorescence (LIF) spectroscopy are non-destructive optical imaging modalities. OCT provides architectural cross-sectional images at near histological resolutions and LIF provides biochemical information. We utilize combined OCT-LIF to image ovaries in post-menopausal ovarian carcinogenesis rat models, evaluating normal cyclic, acyclic and neoplastic ovaries. Eighty-three female Fisher rats were exposed to combinations of control sesame oil, 4-vinyl cyclohexene diepoxide (VCD) to induce ovarian failure,and/or 7,12-dimethylbenz[a]anthracene (DMBA) to induce carcinogenesis. Three or five months post-treatment, 162 ovaries were harvested and imaged with OCT-LIF: 40 cyclic, 105 acyclic and 17 SCST. OCT identified various follicle stages,corpora lutea (CL), CL remnants, epithelial invaginations/inclusions and allowed for characterization of both cystic and solid SCST. Signal attenuation comparisons between CL and solid SCST revealed statistically significant increases in attenuation among CL. LIF characterized spectral differences in cyclic, acyclic and neoplastic ovaries attributed to collagen, NADH/FAD and hemoglobin absorption. We present combined OCT-LIF imaging in a rat ovarian carcinogenesis model, providing preliminary criteria for normal cyclic, acyclic and SCST ovaries which support the potential of OCT-LIF for ovarian imaging.

Occurrence of endometrial glandular dysplasia precedes uterine papillary serous carcinoma.

Endometrial glandular dysplasia (EmGD) is a newly defined entity that is commonly and specifically associated with serous endometrial intraepithelial carcinoma and uterine papillary serous carcinoma (UPSC). Endometrial glandular dysplasia has been proposed as a true precancerous lesion of UPSC based on our recent studies showing morphological and molecular linkages between these 2 lesions. The present report is to examine if EmGD occurs before UPSC development and to define the period from the occurrence of EmGD to a full-blown UPSC by studying their clinicopathologic features in a retrospective setting. A total of 250 UPSC and 258 benign cases were used as initial study source. To identify if EmGD existed before the development of UPSC, we blindly reviewed all available endometrial biopsies from a period of 3 months or earlier before hysterectomies. These included an available pool of 27 biopsy specimens from UPSC group and 29 samples from benign control group. Any endometrial abnormalities, which morphologically qualified as EmGD as defined previously in preceding biopsies were recorded. Among all endometrial biopsies before hysterectomies, we morphologically identified a total of 10 EmGD cases; 9 (33%) of 27 were from UPSC group and 1 (3.5%) of 29 were from benign control group. All 10 morphologically diagnosed EmGD cases showed a high p53 staining score (>/=5) except 1 noncontributory from UPSC group and 1 from the benign control group with a score of 0. A high MIB-1 index score was seen in all EmGD cases, whereas low index was found in morphologically benign biopsies. The main purpose of this study is to report these retrospectively identified EmGD cases. The period from identifying EmGD to the presence of either a serous endometrial intraepithelial carcinoma or a full-blown UPSC ranged from 16 to 98 months with an average of 33 months. We conclude that occurrence of EmGD precedes the development of UPSC. The findings support our recently proposed UPSC development model, in which EmGD is likely to be a precursor lesion of UPSC. Further studies are needed to address issues in regard to molecular and cellular mechanisms, reversibility, risk of UPSC development, and clinical management of EmGD.

Karyometry of infiltrating breast lesions.

OBJECTIVE: To characterize nuclei from well-differentiated, moderately differentiated and poorly differentiated lesions of invasive breast cancer by karyometry and to test the hypothesis that these diagnostic categories form homogeneous sets. STUDY DESIGN: Histopathologic sections from 6 cases of well-differentiated, 11 cases of moderately differentiated and 17 cases of poorly differentiated ductal carcinomas were digitally recorded. From each case 100 nuclei were segmented and analyzed by karyometry. A discriminant analysis was performed, and nuclear and lesion signatures were computed. The nonsupervised learning algorithm P-index was applied. A progression curve per diagnostic category based on mean nuclear abnormality and a discriminant function score was derived. RESULTS: The well-differentiated lesions formed a homogeneous set, but both the moderately and poorly differentiated lesions showed 2 significantly different subpopulations with nuclei of substantially different nuclear abnormality and progression. CONCLUSION: The visual histopathologic diagnostic assessment of these lesions was based on an evaluation of both tissue architectural criteria and nuclear criteria. Here, only the pattern of nuclear chromatin was evaluated. Cases belonging to the same diagnostic category as assessed by their differentiation may be further characterized by the extent to which the nuclei deviate from normal. There was substantial case-to-case heterogeneity in these invasive lesions.

Attitudes of individuals with acquired brain injury towards disability.

OBJECTIVE: To describe the relationships between acceptance of disability, attitudes towards disability, quality of life, functional ability, community integration, and demographic markers, in individuals with acquired brain injuries. METHOD: Forty subjects completed four self-report instruments, including the Attitudes Towards Persons with Disabilities Scale O-Version, the Acceptance of Disability Scale, the Rand-36 Health Status Inventory, and the Community Integration Questionnaire. An observer completed the Functional Independence Measure and the Functional Assessment Measure as a measure of the subject's level of disability. RESULTS: Significant correlations appeared between positive regard for one's own and other's disabilities and one's acceptance of disability, as well as both higher health status and community integration. No significant correlations appeared between positive attitudes and either physical functioning, age, age of onset, or time since injury. CONCLUSION: Situational factors, such as community integration, can be manipulated to potentially influence the attitude of an individual with acquired brain injury towards themselves and towards others with disabilities.

Crisis and its assessment after brain injury.

PRIMARY OBJECTIVE: To develop a measure to assess crisis after acquired brain injury (ABI). RESEARCH DESIGN: A triangulated research strategy, using both qualitative and quantitative methods, was employed to develop the crisis measure. METHODS AND PROCEDURES: The measure was developed in two phases. In the first phase, by using focus group methodology, the experience of crisis following brain injury was described. The second phase involved developing the questionnaire items, pilot testing the measure and conducting initial reliability testing. MAIN OUTCOMES AND RESULTS: The six themes derived from the content analysis led to the creation of the measure, with versions for individuals who have an ABI, family members and professionals. Test-re-test reliability results (n = 40) were adequate. CONCLUSIONS: The results suggest that crisis is experienced as precarious homeostasis with individuals with brain injury, varying in intensity over time, subjectively viewed as never really absent.

Karyometry in endometrial adenocarcinoma of different grades.

OBJECTIVE: To characterize nuclei from adenocarcinoma of the endometrium of different grades in order to establish whether significantly different nuclear subpopulations exist. STUDY DESIGN: A total of 1,400 nuclei from 14 cases of adenocarcinoma of the endometrium of grades 1, 2 and 3 were recorded, and 600 nucleifrom normal, secretory phase glandular endometrial epithelium were used as a reference data set. Karyometric features were computed and a discriminant function derived to define a trend in feature values for nuclei from lesions of different grades. The nuclei from lesions of different grades were processed by a nonsupervised learning algorithm in an effort to detect and define subpopulations. RESULTS: Nuclei from grade 1 lesions represented a near-diploid stemline, whereas nuclei from grade 3 lesions formed an aneuploid set with a mode around 3N. The existence of three subpopulations with statistically different nuclear chromatin patterns could be shown for nuclei from each grade. In each grade these three subpopulations occupied the same relative position in feature space. For grade 1 lesions all three subpopulations were near diploid, for grade 3 lesions all three were approximately triploid. CONCLUSION: The nuclei in adenocarcinoma of the endometrium form a heterogeneous set, with subpopulations of distinctly different chromatin patterns and different ploidy. This should be taken into consideration in assessing the efficacy of chemopreventive intervention.

A karyometric approach to the characterization of atypical endometrial hyperplasia with and without co-occurring adenocarcinoma.

OBJECTIVE: To develop a karyometric image analysis approach to distinguishing atypical endometrial hyperplasia with and without co-occurring adenocarcinoma. STUDY DESIGN: Six cases of atypical hyperplasia without and 6 cases with co-occurring adenocarcinoma, 4 cases of normal endometrium and 3 cases of adenocarcinoma were identified. From each case 100 nuclei were measured in representative diagnostic areas identified by an experienced pathologist. Discriminant analyses were performed. An unsupervised learning algorithm was applied to define and characterize different nuclear phenotypes, and those data were used to identify cases with co-occurring adenocarcinoma. RESULTS: Discriminant analysis showed that nuclei from atypical hyperplasia and atypical hyperplasia with co-occurring adenocarcinoma are statistically different. The unsupervised learning algorithm revealed differences in nuclear subpopulations that can be used to correctly identify an estimated 85% of individual cases. CONCLUSION: Nuclei from atypical hyperplasia without and with co-occurring adenocarcinoma have statistically different karyometric characteristics that may facilitate case classification.