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Chemical basis of the electrophoretic variation observed at the alcohol dehydrogenase locus of Drosophila melanogaster.

The amino acid substitution responsible for the different electrophoretic mobility of the ADHs alleloenzyme and the ADHf alleloenzyme of the alcohol dehydrogenase from a Nigerian population of Drosophila melanogaster has been established as lysine (ADHs) for threonine (ADHf). This result is discussed with reference to the charge state model of electrophoretic variation, in conjunction with other know substitutions at this locus. It is concluded that electrophoretic methods should be capable of distinguishing many alleloenzymes which have identical isoelectric points without recourse to explanations involving conformational variability.

Alcohol Oxidoreductases

Radiographic evaluation of endodontic therapy and the influence of observer variation.

In radiographic evaluation of the results of endodontic therapy the development or persistence of periapical radiolucencies often serve as criteria for therapeutic failure. In the present study the influence of inter- and intraexaminer variation on these results was investigated. Three endodontists and three radiologists interpreted periapical conditions and quality of root filling seal in radiographs of 119 endodontically treated roots. Consensus on the presence of periapical lesion was reached in 27% of cases classified as pathologic. In 6% reports of increased width of the periodontal membrane space accorded. The examiners agreed completely on normal periapical conditions in 37% of the cases. On assessing the quality of root filling seal the opinions of observers differed even more. Complete agreement on cases with adequate and defective seal was reached in 25% and 12%, respectively. For the individual examiner the widened periodontal membrane space was the diagnosis most difficult to reproduce. The present study indicates that the large variation noted among clinical and radiographic studies on the results of endodontic therapy could partly be explained by difficulties in defining and maintaining criteria for radiological evidence of periapical disease.

Clinical Competence

Comparison of four articular indices for use in clinical trials in rheumatoid arthritis: patient, order and observer variation.

Using a Latin square design, 4 patients were examined by 4 rheumatologists. Joints were scored for tenderness and inflammation. The Ritchie, the index of the American Rheumatism Association (ARA), the Hart modified Ritchie and a simplified Lansbury index were calculated from the raw data. The results suggest that an articular index consisting of a simple count of tender joints (Hart modified Ritchie) or a simple count of tender or swollen joints (ARA index) are the most reproducible with multiple observers. We suggest that these indices would be most appropriate for multicenter clinical trials.

Arthritis, Rheumatoid

Chest roentgenograms in diagnosis of traumatic rupture of the aorta. Observer variation in interpretation.

A significant p value is not always a good measure of the clinical value of a diagnostic test. By examining interobserver agreement with respect to chest roentgenogram interpretation, we determined which of seven roentgenographic signs statistically associated with traumatic rupture of the aorta (TRA) are most likely to be useful in clinical practice. Four surgeons and two radiologists were asked to interpret individually, in blinded fashion, the initial chest films of 149 trauma patients who had undergone aortography to rule out TRA. Agreement between all observers, as well as between specialty groups, was examined by chi-square and by calculation of Cohen's kappa statistic, which estimates the extent of agreement. Statistically significant agreement (p = .0000) was found between all observers with regard to mediastinal widening and obscuration of the aortic knob, but other comparisons showed no better than random agreement. Of the seven roentgenographic signs associated with TRA, identification of mediastinal widening and obscuration of the aortic knob show the most consistent interobserver agreement and are the most likely to be useful in clinical practice.

Aorta, Thoracic

Observer variation in assessing spinal curvature and skeletal development in adolescent idiopathic scoliosis.

Accurate measurements of spinal curvature and skeletal development are crucial in planning treatment and assessing curve progression in adolescent idiopathic scoliosis (AIS). An inter-rater agreement trial was undertaken to estimate the reliability of measuring these spinal parameters. Two orthopaedic surgeons and two trained technicians from a scoliosis clinic independently read 30 anteroposterior roentgenograms of AIS patients. Skeletal maturity was assessed using the six-point Risser sign scale, and spinal curvature was measured using the method of Cobb. Excellent agreement was observed in evaluating Risser signs (Kappa = 0.8) and primary Cobb angles (intra-class correlation coefficient, Rho = 0.98). The standard deviation of inter-observer error in measuring primary Cobb angles was 2.5 degrees, and the intra-reader error, based on one observer's reassessments of 15 films, was 1.9 degrees. Inter-rater agreement for assessing secondary Cobb angles was much lower (Rho = 0.52) because small curves (less than 20 degrees) were often not noticed. Differences in agreement between surgeons and technicians were relatively minor. These results indicate that personnel trained at this clinic are able to assess these spinal parameters reliably.

Adolescent

Observer variations in the diagnosis of stroke. WHO collaborative study on the control of stroke in the community.

Validity and consistency of the diagnosis of stroke and its types were tested with 60 case reports including 15 diguised duplicates, drawn at random from community-based stroke registers. Seven European, 5 Japanese, and 5 other centers participated the test. The diagnosis of stroke as such (regardless of its type) seems to have been established accurately in all the 3 groups of centers; this leads to the conclusion that the incidence rates of stroke as registered in the participating centers were comparable. The diagnosis of the types of stroke was less reliable, since intra-and inter-observer bias was found in the diagnosis of the identical sample of test cases. In some European centers, the type of stroke was rarely determined, unless objective and definitive evidences were available. The Japanese centers appeared to have diagnosed the type of stroke in a relatively more uniform way between centers, however, the consistency of the diagnosis at separate times was lower. Subarachnoid hemorrhage, when diagnosed, was generally based on firmer gounds. These observations were confirmed in a small number of autopsy-verified cases. These varying diagnostic attitudes introduce false differences. Such "softness" of type-diagnosis must be borne in mind when comparison of type of stroke at different times or between populations is attempted.

Cerebral Hemorrhage

Observer variation in histopathological diagnosis and grading of cervical intraepithelial neoplasia.

To assess the variability among histopathologists in diagnosing and grading cervical intraepithelial neoplasia eight experienced histopathologists based at different hospitals examined the same set of 100 consecutive colposcopic cervical biopsy specimens and assigned them into one of six diagnostic categories. These were normal squamous epithelium, non-neoplastic squamous proliferations, cervical intraepithelial neoplasia grades I, II, and III, and other. The histopathologists were given currently accepted criteria for diagnosing and grading cervical intraepithelial neoplasia and asked to mark their degree of confidence about their decision on a visual linear analogue scale provided. The degree of agreement between the histopathologists was characterised by kappa statistics, which showed an overall poor agreement (unweighted kappa 0.358). Agreement between observers was excellent for invasive lesions, moderately good for cervical intraepithelial neoplasia grade III, and poor for cervical intraepithelial neoplasia grades I and II (unweighted kappa 0.832, 0.496, 0.172, and 0.175, respectively); the kappa value for all grades of cervical intraepithelial neoplasia taken together was 0.660. The most important source of disagreement lay in the distinction of reactive squamous proliferations from cervical intraepithelial neoplasia grade I. The histopathologists were confident in diagnosing cervical intraepithelial neoplasia grade III and invasive carcinoma (other) but not as confident in diagnosing cervical intraepithelial neoplasia grades I and II and glandular atypia (other). Experienced histopathologists show considerable interobserver variability in grading cervical intraepithelial neoplasia and more importantly in distinguishing between reactive squamous proliferations and cervical intraepithelial neoplasia grade I. It is suggested that the three grade division of cervical intraepithelial neoplasia should be abandoned and a borderline category introduced that entails follow up without treatment.

Biopsy

Observer variation in the pathologic diagnosis of malignant lymphoma in Canada.

Biopsies from "poor prognosis" non-Hodgkin's lymphomas were studied to assess diagnostic variations among pathologists. The original diagnosis and the diagnoses of a nationwide panel of local reference pathologists (LRPs) from 104 cases were reviewed and the technical quality of each biopsy evaluated. Using a modified Rappaport classification, there was agreement in 57% of cases among the panel. This increased to 84% when diagnoses were grouped according to Working Formulation grades. Of the 90 cases in which a comparison of the contributing pathologist's diagnosis and the most common panel diagnosis was possible, there was exact agreement in 51% (kappa = 0.311) of cases and agreement regarding WF grade in 68% (kappa = 0.318). Major panel disagreements occurred in 26 (25%) cases, involving the distinction of metastatic anaplastic carcinoma or Hodgkin's disease from non-Hodgkin's lymphoma in 17 cases and follicular versus diffuse architecture in 16 (overlap present). The contributing pathologist had a major disagreement with the panel in 18 cases (20%), of type and frequency similar to those within the panel itself. Poor fixation (complete or partial) was present in 49 cases (47%); this resulted in significantly fewer majority agreements than in the well-fixed group (25% versus 60%, P = 0.020) and also increased rates of disagreement in the diagnosis of lymphoma versus anaplastic carcinoma. Thus improvements in the technical quality of biopsy material could further improve the diagnostic accuracy of lymphoma diagnosis.

Female

The pineal gland of the mole (Talpa europaea L.). II. Ultrastructural variations observed in the pinealocytes during different parts of the sexual cycle.

Changes of some ultrastructural parameters (paracrystalline structures, Golgi apparatus, secretory granules) in mole pinealocytes were quantitatively studied during the various phases of the sexual cycle. An increase in quantity of paracrystalline structures and of the Golgi appratuses was demonstrated during the period of high sexual activity in male pinealocytes and during oestrus, gestation and lactation in female pinealocytes. Moreover, the appearance of vacuoles in female pinealocytes was observed during pro-oestrus. These results seemto demonstrate close relationship between the endocrine activity of the hypophyseo-gonadal axis and the synthesis of some compounds by the pinealocytes. No increase in the quantity of secretory granules was observed during the various phases of the sexual cycle studied. Key words: pinealocytes, mole, sexual cycle, ultrastructure, paracrystalline structure.

Animals

Observer variation in the assessment of patients with rectal cancer.

To examine the reliability of clinical features as possible components of a clinical method of prognostic staging for patients with rectal cancer, the results obtained when two pairs of physicians interviewed and examined a consecutive series of 60 patients with unresected rectal cancer were compared. High levels of agreement between physicians were found for most items of the patient's history, on whether the lesion was palpable, on the distance of the tumor from the anus, on the location and circumferential extent of the tumor, and on whether the tumor was fixed or mobile. Although physicians elicited similar physical signs, their use of terms to describe the rectal lesions varied widely unless agreed-upon criteria were used. There was 63 per cent agreement on the use of descriptive terms among physicians using criteria and only 13 per cent agreement among physicians not using criteria. These results show that prognostically important clinical features in patients with rectal cancer can be reliably identified and are thus suitable for inclusion in methods of clinical prognostic staging for this disease.

Humans

Observer variation in the classification of mammographic parenchymal patterns.

Wolfe has described different cancer risks associated with a classification of four patterns of the breast parenchyma on mammography, but there is however little information available on the ability of radiologists to agree on the classification of the different patterns. We have assessed inter-rater agreement on the assignment of films to one of the four mammographic patterns described by Wolfe. One hundred xeromammograms were selected, copied and distributed to 10 radiologists who were experts in mammography. Films were classified according to the presence or absence of several radiological signs, according to diagnosis and recommendation, and according to mammographic pattern. Agreement was assessed after correction for agreement expected by chance, using the Kappa statistic. In general, high levels of agreement were found for the classification of mammographic pattern. Agreement on the classification of mammographic pattern was substantially greater than agreement for any other feature of mammographic interpretation, including diagnosis and recommendation.

Breast Neoplasms

Dysplasia and deoxyribonucleic acid aneuploidy in the assessment of precancerous changes in chronic ulcerative colitis. Observer variation and correlations.

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.

Adult

Observer variation in the diagnosis of dysplasia in Barrett's esophagus.

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.

Barrett Esophagus