Observer variations in foveal colour vision responses.
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Cancer prevention in patients with long-standing ulcerative colitis depends on the detection of epithelial dysplasia in colorectal biopsy specimens. Deoxyribonucleic acid analysis by flow cytometry has also been used to examine biopsy specimens, and might be a more quantitative method of detecting precancerous change. Histology and flow cytometry were used to analyze 333 paraffin blocks from colectomy specimens of 58 patients with extensive ulcerative colitis; 22 of these patients had developed carcinoma. Interobserver agreement between three experienced pathologists grading the sections was good for high-grade dysplasia and no dysplasia, but poor for low-grade and indefinite dysplasia. Deoxyribonucleic acid aneuploidy was easier to recognize than dysplasia and, as with dysplasia, it was found to be associated with patients who had developed carcinomas. The presence of deoxyribonucleic acid aneuploidy correlated with the presence of dysplasia. We believe that dysplasia is a useful marker of premalignant change and that flow cytometry may be useful as a complement to histologic examination when dysplasia is suspected.
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The potential value of biopsy surveillance of patients with Barrett's esophagus for dysplasia is diminished by a lack of agreement on the diagnostic criteria for dysplasia. In a preliminary consensus conference, experienced gastrointestinal pathologists from four medical centers agreed on criteria for a five-tiered histologic classification of dysplasia in Barrett's esophagus--negative for dysplasia, indefinite for dysplasia, low-grade dysplasia, high-grade dysplasia, and intramucosal carcinoma. Eight morphologists in the four centers tested the criteria for interobserver agreement by examining a set of coded slides that had been chosen to include some especially difficult interpretative problems in all five histologic classifications. Interobserver agreement of 85 and 87% was achieved in successive reviews when the combined group of high-grade dysplasia and intramucosal carcinoma was compared with the combined group of low-grade dysplasia, indefinite for dysplasia, and negative for dysplasia. Comparison of other groups yielded less agreement. For example, negative for dysplasia could be distinguished from all other diagnoses with an interobserver agreement of 72%. We conclude that experienced gastrointestinal morphologists can diagnose high-grade dysplasia and intramucosal carcinoma with a high degree of agreement and thus can detect those patients who may need immediate rebiopsy or esophageal resection. Either further refinement of histologic criteria or alternate diagnostic methods will be needed to achieve the reproducible diagnosis of indefinite changes and low-grade dysplasia. This is important because patients with such changes theoretically merit closer endoscopic surveillance.
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OBJECTIVES: In women, the gonadotrophin response to gonadotrophin-releasing hormone (GnRH) displays a circadian rhythm during the early follicular phase (EFP), with GnRH-stimulated luteinizing hormone (LH) and follicle-stimulating hormone (FSH) release found to be markedly decreased at night. Since the opioidergic inhibition of gonadotrophin secretion is selectively enhanced at night, we reasoned that the circadian changes in the gonadotrophin responsiveness to GnRH might be related to a nocturnal increase of opioidergic activity. STUDY DESIGN: Eleven women with normal menstrual cycles were studied in the EFP on four different occasions in random order. Studies were conducted either during the day (0900-1300 h) or at night (2100-0100 h). During these times, GnRH (25 micrograms i.v.) was administered in conjunction with either saline (as control) or naloxone (4 mg i.v.). MEASUREMENTS: Frequent blood samples were obtained before and after GnRH stimulation for determination of basal sex steroid and gonadotrophin concentrations by immunoradiometric assays. RESULTS: While oestradiol levels were comparable (P > 0.3) at all times, progesterone concentrations were significantly (P < 0.01) higher during day than during night hours, with no difference between control and naloxone conditions. Gonadotropin responses to GnRH stimulation were not significantly different between day and night times, nor did they vary between control and naloxone conditions. CONCLUSIONS: Opioidergic blockade imposed by naloxone did not noticeably change GnRH-stimulated gonadotrophin release at any of the study times. We therefore infer that mechanisms other than a nocturnal increase of opioidergic inhibition may account for eventual circadian changes in the gonadotrophin responsiveness of early follicular phase women.
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An improved method of analysing interobserver variation in histopathological studies is described and illustrated, by use of data from a congruence survey of malignant melanoma. The method provides, between any number of pathologists, an assessment of overall agreement and of agreement on each individual category of a classification system. Adjustment for differences in chance agreement due to varying numbers of categories or an altered composition of cases is included in the analysis. A generalization of the procedure designed to measure the strength of associations between different categories is formulated and explained with the use of an example.
Levels of agreement between nine pathologists on the Rye classification of Hodgkin's disease and on diagnostic subcomponents used in applying the classification, were analysed by kappa statistics. Pathologists experienced comparatively little difficulty in agreeing on the presence of nodules and lacunar cells and hence best agreement was achieved on the nodular sclerosis category. Poorer agreement levels on the lymphocytic predominance, mixed cellularity and lymphocytic depletion categories were explained mainly by problems in the assessment of numbers of lymphocytes and abnormal reticulum cells other than Reed-Sternberg cells. Identification of the Reed-Sternberg cell, although of paramount importance to a diagnosis of Hodgkin's disease, appeared to have no great practical relevance to use of the Rye classification in this series of cases.
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Fetal alcohol syndrome (FAS) is characterized by growth retardation, mental deficiencies, and numerous craniofacial and neuronal anomalies; the type and severity of these defects may be related to the time and dose of maternal ethanol exposure. Ethanol administered during presomitic stages results in the typical FAS craniofacial phenotype and is accompanied by a loss of cranial neural crest cells (CNCCs) through ethanol-induced cell death. However, the stage-specific effects of ethanol on the CNCC population is unknown. We examined the effects of ethanol on CNCC populations by treating in ovo chick embryos with a single ethanol dose (0.43 mmol/egg) at various stages of CNCC development, and corresponding to the first 3-4 weeks of human gestation. Ethanol treatment induced cell death and reduced CNCC populations in patterns consistent with observed dysmorphologies of CNCC-derived cranial structures. The precise population affected was dependent on the timing of ethanol exposure. Treatment at gastrulation or neurulation induced cell death and losses of CNCC populations, particularly those in rostral positions, and resulted in more severe craniofacial defects. In contrast, treatment at early somitic stages (4-16 somites) induced cell death, primarily within caudal CNCC populations, but resulted in less severe craniofacial defects, suggesting an increased capacity for recovery. These results suggest that there are distinct developmental windows during which the CNCCs may be particularly susceptible to ethanol-induced cell death. We conclude that ethanol exposure seems to affect specific events adversely during neural crest development. The timing of embryonic ethanol exposure relative to CNCC development could account, in part, for the heterogenous craniofacial defects observed in FAS.
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