The observer variation in the measurement of arterial blood pressure.
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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.
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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The size of the liver and spleen of 32 patients was assessed by four clinicians from a clinical examination and by four radiologists from a plain radiograph of the abdomen. The latter assessment was found to be subject to less variation than the former, particularly in regard to the liver. Large livers and spleens were more easily seen radiologically than small ones. Most of the variation among the radiologists arose because of the 6% and 24% of cases in which the liver and spleen, respectively, were poorly seen on the radiograph. It is concluded that a plain radiograph of the abdomen, including the diaphragm and with the costal margin indicated, is a useful adjunct to clinical examination.
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The aim of quality control of a laboratory investigation is to ensure that similar results are obtained on the same material at different centres. To investigate its practicability in cytodiagnosis, the same cytological material was examined independently at six centres. Each centre supplied material from 20 cases, providing a total of 120 cases, ie, 100 cases excluding the donor centre's own material. The degree of agreement between the centres was studied using (a) the standard National Health Service cytology report terminology, (b) the centre's own terminology, and (c) the recommended recall time. The results revealed close agreement between five out of six centres in the reports obtained in relation to dysplasia and malignancy, namely, less than 3% false negative results and not more than 1.7% false positive results. The recommended recall time provided a similar order of agreement after discrepancies due to the management of inflammatory conditions had been eliminated. There was marked disagreement in the diagnosis of both presence and type of infection. The results indicate that improvement in the quality of cytological material would increase the consistency of cytodiagnosis. Cytodiagnosis itself, being an expression of opinion, does not appear to be an appropriate field for quality control.
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Sensitivity and accuracy of cytodiagnosis were assessed in a multicentre study. Six centres each provided sputum cytological material from 20 cases. Each centre screened and reported on the 100 slides provided by the other five centres. The reports were assessed against consensus reference diagnoses, reached by discussion with transparencies, histological sections, and closed-circuit television. False positive rates of 0-4% (average 1.3%) and false negative rates of 0-12% (average 5.0%) of slides examined were recorded. The order of agreement on the three common cell types was adenocarcinoma 75% (50-91%), squamous cell carcinoma 80% (59-94%) and small carcinoma 95% (71-100%). The effect of quality of material on cytological opinion was assessed by comparing disagreement rates on each of the different sets of 20 slides. Disagreement varied from 1% to 23% depending on which set of material was examined.
Few areas of immunology have been so controversial as that of suppressor T cells. Studies of T cell clones derived from patients with infectious diseases, including leprosy, and allergies have allowed the delineation of functional human T cell subsets. Both CD4 and CD8 cells can be discriminated into subsets that are differentiated by their functions and patterns of lymphokines. Type 1 CD4 cells reactive with lepromin and PPD produce IFN-gamma and IL-2 predominantly, while Type 2 CD4 clones, specific for tetanus toxoid, produce IL-4 and IL-5. Type 1 CD8 cytotoxic T lymphocytes produce predominantly IFN-gamma and IL-2. T suppressor clones derived from immunologically unresponsive lepromatous leprosy patients are antigen-specific, CD8 cells, HLA-DQ restricted, and produce predominantly IL-4, and were designated Type 2 CD8 cells. Several models for peripheral tolerance based on distinct functional T cell subsets are discussed. Previous models of T cell suppression in the mouse and the reciprocal relationship between humoral and cell-mediated immunity in general are reinterpreted in light of such T cell subset interactions.