Loyd A. West

Accuracy of optical spectroscopy for the detection of cervical intraepithelial neoplasia: Testing a device as an adjunct to colposcopy

Testing emerging technologies involves the evaluation of biologic plausibility, technical efficacy, clinical effectiveness, patient satisfaction, and cost‐effectiveness. The objective of this study was to select an effective classification algorithm for optical spectroscopy as an adjunct to colposcopy and obtain preliminary estimates of its accuracy for the detection of CIN 2 or worse. We recruited 1,000 patients from screening and prevention clinics and 850 patients from colposcopy clinics at two comprehensive cancer centers and a community hospital. Optical spectroscopy was performed, and 4,864 biopsies were obtained from the sites measured, including abnormal and normal colposcopic areas. The gold standard was the histologic report of biopsies, read 2 to 3 times by histopathologists blinded to the cytologic, histopathologic, and spectroscopic results. We calculated sensitivities, specificities, receiver operating characteristic (ROC) curves, and areas under the ROC curves. We identified a cutpoint for an algorithm based on optical spectroscopy that yielded an estimated sensitivity of 1.00 [95% confidence interval (CI) = 0.92–1.00] and an estimated specificity of 0.71 [95% CI = 0.62–0.79] in a combined screening and diagnostic population. The positive and negative predictive values were 0.58 and 1.00, respectively. The area under the ROC curve was 0.85 (95% CI = 0.81–0.89). The per‐patient and per‐site performance were similar in the diagnostic and poorer in the screening settings. Like colposcopy, the device performs best in a diagnostic population. Alternative statistical approaches demonstrate that the analysis is robust and that spectroscopy works as well as or slightly better than colposcopy for the detection of CIN 2 to cancer.

Inhibition of yeast phagocytosis by dexamethasone in macrophage cultures: reversibility of the effect and enhanced suppression in cultures of stimulated macrophages.

This investigation was initiated to characterize further the ability of 1 microM dexamethasone to suppress the ingestion of heat-killed Saccharomyces cerevisiae particles in cultures of murine resident peritoneal macrophages. Time course studies revealed that the inhibitory response required the continual presence of the steroid in the culture medium. In addition, increased inhibitory responses occurred after dexamethasone was supplied to previously untreated cultures of resident macrophages that became stimulated by differentiating in vitro. These findings indicate that glucocorticoids act directly on macrophages to decrease their phagocytic capacity, which in vivo would reduce host resistance.

Modulatory effects of heat-labile serum components on the inhibition of phagocytosis by dexamethasone in peritoneal macrophage cultures.

This investigation examined the effects of heat-labile serum substances on the suppression of yeast phagocytosis in dexamethasone-treated cultures of murine resident peritoneal macrophages. When 4-6 day old untreated control cultures were supplemented with either heat-inactivated (56 degrees C, 30 min) or intact (non-heat-inactivated) fetal bovine serum, more than 90% of the macrophage population ingested at least 1 yeast particle during 15 min phagocytosis assays. In cultures treated with 10(-6) M dexamethasone, approximately 30% of the macrophages were phagocytic. In contrast, approximately 70% of the steroid-treated population consisted of phagocytes in cultures supplemented with intact serum. Medium shift experiments demonstrated that the type of serum present during the 15 min yeast phagocytosis assays, but not the 4-6 day incubation periods, determined the size of the phagocytic subpopulations in the treated cultures. Whereas the majority of control phagocytes ingested more than 8 yeast particles, most dexamethasone-treated phagocytes ingested far fewer than 8 particles regardless of the size of the phagocytic subpopulations. In contrast to yeast, the ingestion of latex particles was inhibited to the same extent in dexamethasone-treated cultures that contained either heat-inactivated or intact serum. Thus, dexamethasone action impairs the ability of macrophages to accumulate yeast particles even though the phagocytic subpopulation is larger in treated cultures containing intact serum. This larger subpopulation may result from the activation of the alternative complement pathway by yeast during phagocytosis.

Use of Nuclear Morphometry Characteristics to Distinguish between Normal and Abnormal Cervical Glandular Histologies

This is a methodological study exploring the use of quantitative histopathology applied to the cervix to discriminate between normal and cancerous (consisting of adenocarcinoma and adenocarcinoma in situ) tissue samples. The goal is classifying tissue samples, which are populations of cells, from measurements on the cells. Our method uses one particular feature, the IODs‐Index, to create a tissue level feature. The specific goal of this study is to find a threshold for the IODs‐Index that is used to create the tissue level feature. The main statistical tool is Receiver Operating Characteristic (ROC) curve analysis. When applied to the data, our method achieved promising results with good estimated sensitivity and specificity for our data set. The optimal threshold for the IODs‐Index was found to be 2.12.