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Observer reproducibility in grading dysplasia in colorectal adenomas: comparison between two different grading systems.

The two most well known and well defined grading systems for dysplasia in colorectal adenomas were compared with regard to reproducibility. The Konishi-Morson system (KMS) operates with several histological and cytological variables and grades of mild, moderate, and severe dysplasia. The Kozuka system is based on the extent of nuclear pseudostratification and also has three grades of dysplasia (III-V). As the group of severe dysplasia is very large in this system, it was extended with two higher grades, similarly based on individual histological criteria, known hereafter as the extended Kozuka system (EKS). Fifty six adenomas were graded by two observers, each observer grading twice according to the KMS criteria and twice according to EKS criteria. Intraobserver reproducibility was excellent for the KMS and moderate for the EKS, but this was not significant. The overall interobserver reproducibility was similar (moderate) for the KMS and for the EKS. Kappa values for interobserver reproducibility on individual categories were excellent for severe dysplasia according to the KMS, but low for all other categories in both systems. By simplifying both systems into two groups a high reproducibility can be obtained, but this implies that all the original grades (III-V) for the EKS must be grouped together. It is therefore recommended that a simplified KMS is used for further studies on the biological importance of dysplasia and for comparison between histological changes and other markers for colorectal neoplasia.

Adenoma

Reproducibility of measurements of coronary narrowings by videodensitometry and by digital calipers.

Computer-assisted videodensitometry has been shown to be a reliable and reproducible method of measuring absolute and relative coronary narrowings. Using a commercially available analyzer (Vanguard XR70) we confirmed intra- and interobserver reproducibilities in 34 narrowings in 9 patients. Analyses were performed on normal area and diameter, stenotic area and diameter, percent area stenosis and percent diameter stenosis. For all 6 analyses, excellent intra- and interobserver correlations were found (r = 0.93-0.98), with slopes close to 1 and intercepts close to zero. Caliper measurements (Mitutoyo Digimatic) of the same lesions by the same observers showed good inter- and intraobserver reproducibility for percent diameter stenosis (r = 0.90 and 0.86), with mean interobserver difference of 1.67 +/- (SD) 6.4% and intraobserver difference of 2.97 +/- (SD) 7.9%. However, less good correlations were found between caliper and videodensitometric measurements of percent diameter stenosis; r = 0.61 and 0.76 for the two observers. These data suggest that videodensitometry is a highly reproducible quantitative angiographic method, suitable for documenting changes in the severity of coronary artery lesions, both spontaneous or related to interventions. Caliper measurements do not provide the same degree of accuracy, but they have acceptable reproducibility in measuring diameter stenosis. As such, they are also suitable for assessing changes in severity of coronary artery lesions in individual patients.

Angioplasty, Balloon, Coronary

Reproducibility studies with the Zeiss SLC system and animal cataract models.

Scheimpflug photography has become the basic method for documentation of lens transparency changes in clinical and experimental ophthalmology, due to its high reproducibility. In animal cataract studies, the reproducibility is strongly influenced by the handling characteristics of the camera used, due to limited cooperation of the animal. The reproducibility of the Zeiss SLC system, which offers a direct quality control of the image on the video screen, was tested with 2 animal cataract models, the ultraviolet B (UVB)-induced cataract and the true diabetic cataract in the Brown-Norway rat. 10 rats each of the 2 cataract models and of an untreated control group were photographed in a random order on 3 occasions on the same day by the same photographer. Quality control and densitometry were performed by the same system operator, the measurement window was positioned standardly, coincident with the optical axis of the eye. Statistical comparison was carried out in the capsular layer, that is the area of initial cataract development in both models, and in the cortical layer, into which the diabetic cataract progresses during its later stages of development. The nuclear layer was also evaluated, but has no direct relation to one of the models employed. The results clearly indicate that the reproducibility is predominantly influenced by the homogeneity or inhomogeneity of the cataract model employed. The system operator and the photographer provided that they are well trained, have minor influence on the reproducibility of the Zeiss SLC system.

Animals

A protocol for performing reproducible methacholine inhalation tests in children with moderate to severe asthma.

Reproducibility of methacholine inhalation tests (MIT) over a 2-wk period has been established in adult populations, but similar studies demonstrating reproducibility in children are lacking. We set out to establish the reproducibility of MIT in children as a prerequisite for a study of the natural history of airway hyperreactivity in asthmatic children. Most inhalation testing is done in persons with mild asthma because the recommended time interval for the withholding of medications prior to bronchial challenge is poorly tolerated by more labile asthmatics. In order to evaluate asthmatics with more severe disease, we modified a standardized method of methacholine inhalation to include a three-tier pretest medication regimen and investigated the reproducibility of this MIT protocol in 11 children as young as 6 yr of age. The three tiers were designed to keep baseline FEV1 greater than or equal to 70% predicted since diminished baseline airway caliber may affect MIT results. Eight of the 11 children were bronchodilator-dependent, and two of the eight also required inhaled steroids. Eleven children (6 to 13 yr of age) underwent MIT, between December and March, 1 day, 1 wk, and 1 month after an initial test. The PD20FEV1 using cumulative breath units (BU) were compared. The range of PD20FEV1 in the 11 children was 0.27 to 14.4 BU, with nine subjects classified as severe (PD20FEV1 less than 2.5 BU). We found a high degree of reproducibility of MIT. The interest correlation coefficient (r) was 0.98 after 1 day, 0.95 after 1 wk, and 0.96 after 1 month.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent

Long-term reproducibility of respiratory gas exchange measurements during exercise in patients with stable cardiac failure.

Present-day technology has greatly facilitated the monitoring of respiratory gas exchange in the clinical exercise laboratory. Despite the growing use of these techniques to assess the severity and progression of disease or therapeutic response in patients with heart failure, the long-term reproducibility of oxygen uptake (VO2), carbon dioxide production, minute ventilation, heart rate (HR), and blood pressure at rest and during incremental exercise in such patients, to our knowledge, has not been evaluated. Therefore, the purpose of this study was to quantify the reproducibility of these variables along with exercise duration, maximum VO2 (VO2max) and anaerobic threshold in a group of 16 patients (61 +/- 7 years, 14 male) with chronic, stable cardiac failure of varying severity and etiology who had five or more incremental treadmill exercise tests over a period of time that ranged from 3 to 22 months. For each variable, reproducibility was represented by the coefficient of variation (CVAR). Except for exercise duration, CVAR was not a function of the severity of heart failure and, for all variables, patient-to-patient variation in CVAR was approximately 9 percent. The maximum CVAR for HR, systolic blood pressure, VO2, and VO2max was generally below 10.5 percent and for exercise duration and anaerobic threshold it was less than 12.5 percent. Based on this retrospective analysis, it is concluded that reproducible respiratory gas exchange and HR exercise responses are obtainable over extended periods of time in patients with stable, chronic cardiac failure. Exercise duration, however, is less reproducible in patients with moderate to severe failure.

Aged

Reproducibility of ambulatory gastric pH recordings in the corpus and antrum. Effect of food, time, and electrode position.

The reproducibility of simultaneous, long-term, ambulatory gastric pH recordings in the antrum and corpus was investigated in nine healthy subjects who underwent three separate, 27-h gastric double pH-metries. Intraindividual reproducibility for the entire 27-h recording period was good in the corpus (Kendall's concordance coefficient, W' = 0.6393, p less than 0.025) but not in the antrum (W' = 0.4806, NS). Analysis of predefined time periods showed that non-meal daytime pH was reproducible in the corpus (W' = 0.6531, p less than 0.025) but not in the antrum (W' = 0.3395, NS), whereas mealtime pH was reproducible in the antrum (W' = 0.7159, p less than 0.005) but not in the corpus (W' = 0.4954, NS); nocturnal pH was not reproducible in either the antrum or the corpus. These results reflect the functional separation of corpus and antrum and their differing responses to food. Thus, studies of gastric acidity over long periods should be conducted in the corpus, whereas studies of gastric acidity over shorter, meal-related periods should be conducted with a second electrode in the antrum.

Adult

Reproducibility of a semiquantitative food frequency questionnaire to assess the intake of fats and cholesterol in The Netherlands.

The reproducibility of a 104 item semiquantitative food frequency questionnaire to estimate the intake of energy, fat, fatty acids and cholesterol was assessed in a group of 93 men and women in the Netherlands. The questionnaire was administered by trained interviewers. Subjects were asked to recall the consumption of 104 items during the past month. A second interview was conducted 8 weeks later. The mean difference in nutrient intake between the two assessments was very small, with a maximum of 5% for cholesterol intake, but the variance of individual differences was considerable. Pearson correlation coefficients between two assessments 8 weeks apart ranged from 0.71 for polyunsaturated fatty acids intake (when expressed as percentage of energy intake) up to 0.91 for energy intake. The reproducibility was found to be similar in males and females. Reproducibility was assessed for separate food items as well as for 20 food groups. Items consumed were often highly reproducible and rarely had a poor reproducibility. This food frequency questionnaire is considered to be a suitable tool to estimate and monitor the intake of fat, fatty acids and cholesterol in the Netherlands.

Adult

A comparison of six different ways of expressing the bronchodilating response in asthma and COPD; reproducibility and dependence of prebronchodilator FEV1.

Various indices are used to express the bronchodilating response. It is unclear, however, which index is most informative. The aim of this study was to compare six expressions of the bronchodilating response and to examine: 1) the independence of the prebronchodilator forced expiratory volume in one second (FEV1); and 2) the reproducibility of the bronchodilating response. Bronchodilating responses (increases in FEV1 60 min after salbutamol 400 micrograms and ipratropium bromide 80 micrograms) on six test occasions, during two years, of 183 patients (72 asthma, 111 chronic obstructive pulmonary disease (COPD)) from a large bronchodilator intervention study were used. The dependence of the prebronchodilator FEV1 was investigated both between patients (cross-sectional analysis) and within patients (longitudinal analysis) by means of linear regression analysis. The reproducibility of the bronchodilating response was calculated by means of the coefficients of variation (CVs) of the six bronchodilating responses during two years. The CVs of the six expression indices were compared by analysis of variance (ANOVA). No index was independent of the prebronchodilator FEV1. However, some indices were significantly more dependent on the prebronchodilator lung function and, therefore, less reproducible than others. The "% initial" index (change as a percentage of the prebronchodilator value) was the most dependent on the prebronchodilator lung function and had the worst reproducibility (CV ranged from 50-61%). The "% possible" (change as a percentage of the predicted minus prebronchodilator value) and "% achievable" (change as a percentage of the maximal postbronchodilator minus prebronchodilator value) indices were the least dependent on the prebronchodilator value and had the highest reproducibility (CV ranging from 34-53%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

A reproducible method for producing and quantifying the stages of fracture repair.

Male CD-1 mice, 4 to 6 months of age, were used to establish a reproducible model to study the stages of fracture repair. A custom-designed fracture apparatus was constructed, and trials with it demonstrated its capacity to reliably reproduce a closed fracture of the tibia. Dietary and sleep habits in the treated mice were the same as unfractured control mice. Four stages of fracture repair were documented and the duration of each stage was quantifiable and reproducible. The last stage of fracture repair was completed by 21 days postfracture. The reproducibility of the fracture, the reproducibility of the times and stages of fracture repair, the relatively short time to complete the fracture repair process, and the minimal discomfort which allowed the mice to maintain a normal daily routine, suggest that this is an ideal animal model for studying the fracture repair process.

Animals

Reproducibility of iodine-123-hippuran renoscintigraphy in the normal pig at various flow rates.

Twenty-two pigs with normal kidney function and upper urinary tracts were examined with renoscintigraphies once a week for 4 weeks. In order to study the influence of urine flow on the reproducibility, renoscintigraphies were undertaken during various urinary flow rates. Renal split function was reproducible at any level of and independent of the urinary flow rates. For parenchymal and pelvic mean transit times a normogram was constructed for selected urinary flow intervals. An inverse relationship to urine production was seen. Parenchymal and pelvic transit times were fully reproducible when data were compared in two or three consecutive examinations of the same kidney at the same urinary flow rate. Both parenchymal and pelvic mean transit times were however significantly different (p less than 0.001) in kidneys studied from one urinary flow rate to another. Single kidney hippuran clearance was fully reproducible when compared in the same urinary flow interval. However a significant difference was found (p less than 0.05) when single kidney hippuran clearance was compared in renographies undertaken at different urinary flow intervals. Furthermore the study suggests that the size of hippuran clearance is dependent on the urine production, since an increase in hippuran clearance was seen in relation to increase in urinary flow. In conclusion this pig study showed, that monitoring of the urinary flow rate is extremely important in this very commonly used clinical investigation, and that the investigation should be performed in the same state of hydration at any renography to obtain reproducible results.

Animals

[Reproducibility of the Doppler spectrum of the left ventricular stroke volume].

The left ventricular stroke volume was determined in 15 healthy male volunteers of the same age (21-23 yrs). The systolic function was characterized by six, the diastolic function by five parameters. The diameter and the cross-sectional areas of the outflow tract were determined. Intraobserver, interobserver and day-to-day variability of these parameters were investigated. The reproducibility was tested by 4 statistical methods. The significance of the differences between the mean values was determined, as well as the percentual difference of the mean values and of the variation coefficients. Linear regression analysis was done and the correlation coefficient was determined for each parameter. The variation coefficient could be regarded as the best statistical method for characterizing the reproducibility. Thus the simplest, directly measured Doppler parameters gave the best reproducibility. The reproducibility of the complex, calculated parameters was poorer. Comparing the intra- and interobserver reproducibility error, the former one was less.

Adult

Dysplastic melanocytic nevi: a reproducible histologic definition emphasizing cellular morphology.

Histologic criteria commonly used to diagnose dysplastic melanocytic nevi (DMN) have not been correlated adequately with biology nor subjected to rigorous reproducibility studies. To address these failings, we developed histologic definitions emphasizing cellular morphology based on the appearance of typical melanocytes in sun-protected buttock skin, fully-evolved atypia in the vertical component of metastasizing primary cutaneous melanomas, and slight and moderate degrees of atypia defined within these limits in selected varieties of DMN. Reproducibility of our histologic definitions were tested by using two pathologists working independently to assess single routine tissue sections of 19 melanocytic lesions on two occasions at least 6 mo apart. Lesions included five previously diagnosed primary invasive cutaneous melanomas, seven lesions selected for gross morphologic features characteristic of DMN, and four solar lentigines and three common acquired nevomelanocytic nevi preselected for typical appearance and stable growth history. For the primary pathologist using the grading scheme, agreement rates between first and second readings were 84% for final diagnosis and 79% for the highest degree of cellular atypia; for the secondary pathologist, agreement rates for first and second readings for both parameters were 84%. Agreement rates comparing second readings of final diagnosis and highest degree of cellular atypia by the two pathologists were 89% and 79%, respectively. Most of the architectural and host response features commonly associated with DMN were less reproducible. In conclusion, we demonstrated very good reproducibility of histologic definitions used to differentiate the intraepidermal component of DMN from that of melanoma and benign melanocytic and nevomelanocytic hyperplasias, based on a biologic correlation emphasizing cellular morphology. Reproducible histologic definitions are a requisite first step in defining a clinical-pathologic correlation for DMN.

Adolescent

Accuracy and reproducibility of instrumented knee-drawer tests.

Instrumented devices for knee-drawer tests have become popular in orthopaedics relatively recently. The objective of the present study was to document the effects of several parameters on the accuracy and reproducibility of anterior-posterior (AP) drawer measurements. An instrumented knee-drawer tester for AP laxity evaluations was constructed, based on the differential displacement method, measuring shifts of the tuberosity relative to the patella. The accuracy of the AP-shift was determined with the parallel use of a highly accurate roentgen stereo photogrammetric (RSP) measurement system on two postmortem leg specimens. The effects of relative motion between patella and femur were negligible. In addition to AP shifts, significant knee flexion and tibial rotations occurred, although the foot and the thigh were fixed as well as possible. The differential displacement method was effective in circumventing this problem. The accuracy of the AP shift was greater than 10%. The reproducibility of the AP drawer parameters (shifts and compliances) was determined in normal subjects and patients. Tests were made to evaluate the effects of different observers, time sequences, and different days. In addition, effects of muscle relaxation were studied. Overall, the shift parameters at different forces were found to be reproducible to between 5 and 15%. The slopes (compliances) of the laxity curves, at different forces, were found to be reproducible between 20 and 40%. The reproducibility was principally affected by deviations in the subject positioning procedure.

Biomechanical Phenomena

Reproducibility of relaxation and spin-density parameters in phantoms and the human brain measured by MR imaging at 1.5 T.

The reproducibility of T1, T2, and proton density, measured in phantoms and the human brain was evaluated by proton imaging techniques. The sequence used to derive T1 and density values was a multiple-saturation recovery which consists of four pairs of 90 degrees pulses, followed by a 180 degrees phase reversal pulse, generating four T1-weighted images. T2 was derived from a multiple-echo sequence, generating four T2-weighted images. The data were analyzed by fitting the pixel intensities to the respective equations by means of nonlinear multiparameter least-squares analysis. Short-term reproducibility between four consecutive scans was evaluated to be 1-4% depending on location with a phantom covering the entire span of physiologic T1 and T2 values. A second phantom containing a series of identical samples served to study the dependence of the apparent T1 and T2 on position, both radially and axially, with respect to magnet isocenter. Reproducibility across the field of view was found to be better than 7% (T1 and T2). This phantom was further used to evaluate effects of long-term reproducibility, which at each location varied from 5-14% (T1) and 2-10% (T2). Finally, interinstrument reproducibility, tested by means of the same protocol on three different instruments, all operating at the same magnetic field and using largely identical hardware for each location, was found to be 1-14% (T1) and 2-10% (T2). The positional dependence of the apparent relaxation times appears to be systematic and may be due to variations in the effective field, caused by magnet and rf inhomogeneity. Finally, brain tissue relaxation and spin-density data were determined using the same protocol in 37 scans performed on 27 normal volunteers. The tissues analyzed were putamen, thalamus, caudate nucleus, centrum semiovale, internal capsule, and corpus callosum. Excellent accordance was further obtained between left and right hemispheres.

Brain

Ambulatory 24-hour esophageal pH monitoring. Reproducibility and variability of pH parameters.

If 24-hour esophageal pH monitoring is to be a useful diagnostic tool, it must reliably discriminate gastroesophageal reflux patients despite daily variations in distal esophageal acid exposure. To address this issue, we studied 53 subjects (14 healthy normals, 14 esophagitis patients, and 25 patients with atypical symptoms) with two ambulatory pH tests performed within 10 days of each other. Intrasubject reproducibility of 12 pH parameters to discriminate the presence of abnormal acid reflux was determined. As a group, the parameters of percent time with pH less than 4 (total, upright, recumbent) were most reproducible (80%). Therefore, a subject was defined as having gastroesophageal reflux disease if at least one of these three values were abnormal. Intrasubject reproducibility for the diagnosis of reflux disease was 89% for the entire sample. Among subsets, the reproducibility was 93% for the normals and esophagitis patients and 84% for the atypical symptom patients. Total percent time with pH less than 4 was the single most discriminate pH parameter (85%) and nearly equaled that of the three combined parameters (89%). The intrasubject variability of this parameter was determined by the mean +/- 2 SD of the relative differences between the two test results for all 53 subjects. Total percent time with pH less than 4 may vary between tests by a factor of 3.2-fold or less (218% higher to 69% lower). We conclude: (1) ambulatory 24-hr esophageal monitoring is a reproducible test for the diagnosis of gastroesophageal reflux disease; and (2) the large intrastudy variability in 24-hr total acid exposure may limit this test's usefulness as a measurement of therapeutic improvement.

Adult

Reproducibility of incremental maximal cycle ergometer tests in patients with mild to moderate obstructive lung diseases.

This study was designed to examine the reproducibility and the learning effects of incremental maximal cycle ergometer testing in patients with obstructive lung diseases who are untrained and have never done such a test before. Eleven patients were studied on 2 consecutive days with an interval of 24 h. The reproducibility (expressed in relative duplicate error) of most of the parameters tested was good: workload (watt) 4.5%, maximal oxygen consumption (VO2max 3.5%, gas exchange ratio (R) 3.4%, and heart rate 3.7%. Moderate reproducibility was found in maximal ventilation (VEmax) 6.6%, carbon dioxide production (VCO2max 6.0%, and respiration frequency (RF) 8.3%. The reproducibility of the time between the start of the test and the minimum value of VE/VO2 and VE/VCO2 was low. We concluded that in these patients the results of incremental cycle ergometer testing showed good reproducibility in a test-retest procedure. There were no learning effects.

Adult

Reproducibility of exercise-induced ventricular arrhythmia after myocardial infarction.

To evaluate the reproducibility of exercise-induced ventricular arrhythmia, 155 men with a mean age of 53 +/- 8 years underwent serial exercise testing 3 to 52 weeks after myocardial infarction. The reproducibility of categorical test responses, that is, the presence or absence of ventricular arrhythmia, was evaluated with the kappa coefficient, which considers negative as well as possible test responses and expresses reproducibility above the chance level. Reproducibility was highest at an intertest interval of 1 to 5 days and was not enhanced by further categorizing premature ventricular complexes as simple or complex based on their frequency or configuration. Continuous response measures such as frequency of premature ventricular complexes yielded higher reproducibility than categorical responses. Continuous response measures appear preferable to categorical responses for evaluating the clinical significance and response to antiarrhythmic therapy of ventricular arrhythmias.

Arrhythmias, Cardiac

Effects of occlusal therapy on pantographic reproducibility of mandibular border movements.

A clinical experiment was undertaken to study the relationship between occlusal therapy and pantographic reproducibility. Twenty-six subjects were categorized according to their ability to reproduce pantographic border movements and were put into either a control nonreproducible, control reproducible, or experimental nonreproducible group. From each subject a sequence of five pantographic surveys consisting of two morning and two afternoon pantographic recordings was taken. Each survey period lasted a minimum of 30 days. The experimental subjects alone were given occlusal splint therapy and occlusal adjustment therapy during the sequence of recall periods. The relationship between the effect caused by occlusal therapy and pantographic reproducibility was analyzed. For the purpose of analysis, the pantographic recordings were assessed a numerical score using a pantographic reproducibility index. A double-blind technique was used until all data were collected.

Adult