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PubMed2000

Reproducibility and effect of levodopa on dopamine transporter function measurements: a [18F]CFT PET study.

The objective of this article was to study the reproducibility and effect of levodopa on dopamine transporter function measurements using 2beta-carbomethoxy-3beta-(4-[18F]fluorophenyl)tropane ([18F]CFT) positron emission tomography (PET). Seven de novo patients with Parkinson's disease (PD) were studied twice, before and after three months of levodopa medication. Eight healthy volunteer subjects participated in the reproducibility study. The [18F]CFT PET scan was done twice with an interval of approximately 2.5 months. The regions of interest (anterior and posterior putamen, caudate nucleus, and cerebellum) were drawn on individual magnetic resonance imaging (MRI) images, matched with the PET images, and copied onto the PET images. The [18F]CFT uptake was calculated as the region-cerebellum:cerebellum ratio at 180 to 210 minutes. Three-month levodopa treatment in PD patients had no significant effect on [18F]CFT uptake in any striatal subregion between the two PET scans. In PD patients, the percent change from baseline was 4.1% in the anterior putamen, 1.9% in the posterior putamen, and 4.0% in the caudate nucleus. No significant differences in [18F]CFT uptake between the first and second PET scan in any striatal subregion occurred in healthy controls. The intraclass correlation, indicating the reproducibility of the PET scan within subjects, was 0.94 for the anterior putamen, 0.86 for the posterior putamen, and 0.91 for the caudate nucleus. The percent change from baseline was 4.0% in the anterior putamen, 1.1% in the posterior putamen, and 2.8% in the caudate nucleus. Long-term levodopa treatment in PD patients had no effect on the [18F]CFT uptake in the striatum and the test-retest reproducibility was very high. These findings confirm [18F]CFT as a suitable ligand to monitor progression of PD.

Adult↗

PubMed2001

Within-session and between-session reproducibility of cerebral sensorimotor activation: a test--retest effect evidenced with functional magnetic resonance imaging.

The aim of the current study was to assess the reproducibility of functional magnetic resonance imaging (fMRI) brain activation signals in a sensorimotor task in healthy subjects. Because random or systematic changes are likely to happen when movements are repeated over time, the authors searched for time-dependent changes in the fMRI signal intensity and the extent of activation within and between sessions. Reproducibility was studied on a sensorimotor task called "the active task" that includes a motor output and a sensory feedback, and also on a sensory stimulation called "the passive task" that assessed the sensory input alone. The active task consisted of flexion and extension of the right hand. The subjects had performed it several times before fMRI scanning so that it was well learned. The passive task consisted of a calibrated passive flexion and extension of the right wrist. Tasks were 1 Hz-paced. The control state was rest. Subjects naïve to the MRI environment and non--MRI-naïve subjects were studied. Twelve MRI-naïve subjects underwent 3 fMRI sessions separated by 5 hours and 49 days, respectively. During MRI scanning, they performed the active task. Six MRI-naïve subjects underwent 2 fMRI sessions with the passive task 1 month apart. Three non--MRI-naïve subjects performed twice an active 2-Hz self-paced task. The data were analyzed with SPM96 software. For within-session comparison, for active or passive tasks, good reproducibility of fMRI signal activation was found within a session (intra-and interrun reproducibility) whether it was the first, second, or third session. Therefore, no within-session habituation was found with a passive or a well-learned active task. For between-session comparison, for MRI-naïve or non--MRI-naïve subjects, and with the active or the passive task, activation was increased in the contralateral premotor cortex and in ispsilateral anterior cerebellar cortex but was decreased in the primary sensorimotor cortex, parietal cortex, and posterior supplementary motor area at the second session. The lower cortical signal was characterized by reduced activated areas with no change in maximum peak intensity in most cases. Changes were partially reversed at the third session. Part of the test-retest effect may come from habituation of the MRI experiment context. Less attention and stress at the second and third sessions may be components of the inhibition of cortical activity. Because the changes became reversed, the authors suggest that, beyond the habituation process, a learning process occurred that had nothing to do with procedural learning, because the tasks were well learned or passive. A long-term memory representation of the sensorimotor task, not only with its characteristics (for example, amplitude, frequency) but also with its context (fMRI), can become integrated into the motor system along the sessions. Furthermore, the pattern observed in the fMRI signal changes might evoke a consolidation process.

Adult↗

PubMed1992

Limited reproducibility of hourly blood pressure values obtained by ambulatory blood pressure monitoring: implications for studies on antihypertensive drugs.

OBJECTIVE: To assess the reproducibility of average hourly blood pressure values obtained by 24-h non-invasive ambulatory monitoring. PATIENTS: Fifteen outpatients with essential hypertension. In all subjects antihypertensive treatment was withdrawn for 4 weeks before and during the 4 weeks of the study. METHODS: The 24-h blood pressure was monitored by a SpaceLabs 5300 device (four readings per hour during the day and three readings per hour during the night) twice, at a 4-week interval. Systolic (SBP) and diastolic blood pressure (DBP) were averaged for each hour and for the whole 24-h period, and hourly and 24-h reproducibility was quantified by the standard deviation of the mean difference (SDD) between the values obtained in the two recordings. RESULTS: The SDD of hourly SBP and DBP was much greater than that of the 24-h values and ranged widely between the hours of recording. The SDD of hourly SBP and DBP were also variably greater than the SDD of the 24-h value in another 14 untreated essential hypertensives in whom 24-h ambulatory blood pressure was monitored intra-arterially twice at a 4-week interval to calculate hourly average blood pressure on thousands rather than on three or four values per hour. CONCLUSION: Reproducibility is less for hourly than for 24-h average blood pressure. This feature (which probably depends on behavioural differences between two recordings) suggests that ambulatory blood pressure measurement partly loses its advantages for reproducibility and reduction in trial size if the results are analysed over hourly periods.

Adolescent↗

PubMed2004

Reproducibility of intra-arterial ambulatory blood pressure: effects of physical activity and posture.

OBJECTIVE: To examine the effects of physical activity, body posture and sleep quality on the reproducibility of continuous ambulatory blood pressure monitoring. METHODS: Measurements were performed in 35 subjects (18 hypertensive, 11 male), mean +/- standard deviation age 49 +/- 13 years. Blood pressure (BP) was measured in the brachial artery, and beat-to-beat values of systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure and heart rate (HR) were computed. Physical activity and posture were continuously measured with five accelerometers. Subjective quality of sleep was assessed with a questionnaire. Reproducibility was expressed as an intraclass correlation coefficient and as the standard deviation of the within-subject differences. RESULTS: Posture and activity significantly influenced BP and HR. From lying to sitting, the SBP, DBP and HR increased 6 mmHg, 8 mmHg and 8 beats/min, respectively. From sitting to standing these respective increases were 4 mmHg, 2 mmHg and 13 beats/min. A further rise in activity (from standing to moving generally or walking) increased the SBP by 7 mmHg and the HR by 7 beats/min, and decreased the DBP by 8 mmHg. For daytime SBP, DBP and HR, the intraclass correlation coefficient (standard deviation of the within-subject differences) values were 0.93 (7.2 mmHg), 0.94 (3.8 mmHg) and 0.90 (4.1 beats/min). For night-time these respective values were 0.98 (4.4 mmHg), 0.97 (2.5 mmHg) and 0.96 (2.2 beats/min). Correction for physical activity level and posture hardly improved the reproducibility of daytime BP and HR. Reproducibility of night-time BP and HR was not improved by correction for physical activity, supine position or self-reported sleep quality. CONCLUSIONS: Within-subject differences between ambulatory BP recordings cannot be explained by differences in physical activity and body posture.

Adult↗

PubMed1999

Reproducibility of measures of overuse of cataract surgery by three physician panels.

BACKGROUND: Assess the reproducibility of methods to measure overuse of cataract surgery. OBJECTIVES: The objectives of this study are: (1) To determine the extent of agreement about clinical scenarios among, between, and within three physician panels; (2) to apply ratings of clinical scenarios from three panels to actual surgeries; and (3) to assess reproducibility of rates of appropriate use and overuse. METHODS: Three physician panels scored 2,894 clinical scenarios for the appropriate use of cataract surgery. One thousand and twenty charts were abstracted and assigned to the clinical scenario that best corresponded to the patient's clinical situation. Two hundred and fifty nine clinical scenarios were required to assign the cases. Weighted kappa values, confidence intervals, and percentages of agreement were used to measure agreement among, between, and within panels. RESULTS: The all ophthalmologist panel (OP) and the convened multispecialty panel (CM) each rate 92% of the cases as appropriate use, compared with 70% by the mail-in multispecialty panel (MM). The MM have higher uncertain (26% vs. 8% and 7%) and higher inappropriate use (3.5% vs. 0.1% and 1.9%). For the clinical scenarios, the CM and the MM have similar percentages of overuse (6.6%, 7.3%), in contrast to the OP (0.4%). The weighted kappa value for the overall level of agreement about the clinical scenarios among the three panels is 0.53, consistent with moderate agreement. CONCLUSIONS: Study results demonstrate reproducibility for assessment of appropriate use of surgery between the OP and CM. However, both multispecialty panels rate more clinical scenarios as inappropriate use than the ophthalmologist panel. Thus, reproducibility between the CM and the OP may be attributable to the low percentage of overuse of cataract surgery in the study population. The overall level of agreement about the clinical scenarios among the panels is moderate.

Aged↗

PubMed1998

Reproducibility of cardiovascular, respiratory, and metabolic responses to submaximal exercise: the HERITAGE Family Study.

This study determined the reproducibility of cardiovascular, respiratory, and metabolic responses to submaximal cycle ergometer exercise at two power outputs (50 W and 60% VO2max) on each of two separate days in a sample of 390 subjects (198 men and 192 women) participating in the HERITAGE Family Study. The same protocol was conducted across 3 d in an intracenter quality control substudy which included an additional 55 subjects. Reproducibility estimates included technical error, coefficient of variation, and intraclass correlation for each of the selected variables for both subject populations. Further, since the data were collected across four clinical centers, intraclass correlations were also computed separately by clinical center. Most variables were highly reproducible, with coefficients of variation below 9% and intraclass correlations over 0.80. These results were consistent for both subject populations and across all four clinical centers. Reproducibility indicators were generally better at the higher power output. It is concluded that within-subject day-to-day variation and measurement unreliabilities are generally small compared with the between-subject variance in the response to submaximal exercise at each of the clinical centers of the HERITAGE Family Study.

Adolescent↗

PubMed2001

Evaluating the reproducibility and validity of the Aerobic Adaptation Test.

PURPOSE: To examine the reproducibility and validity of a new submaximal, ramped cycle ergometer testing methodology known as the Aerobic Adaptation Test (AAT), which attempts to detect changes in submaximal work capacity and minimize participant discomfort. METHODS: 36 sedentary men (mean age = 48.1 +/- 10.2 yr [SD]) and 22 sedentary women (mean age = 51.9 +/- 10.2 yr [SD]) participated in the study. To test reproducibility, participants were tested twice with an average of 20 d between tests (+/-15 d). To test validity, participants were tested before and after a 6-month physical activity intervention, and outcomes were compared with standard measures of fitness (exercise time and oxygen consumption at 70% max heart rate). The main outcome variable of the AAT was work output (W) over a period of 3 min after reaching 70% maximal heart rate. RESULTS: The average work output at 70% HRmax was highly reproducible, with a test-retest reliability of rho = 0.85 (P < 0.001). Average work output at 70% HRmax significantly increased after 6 months of physical activity intervention (87.8 +/- 32.9 W vs 95.5 +/- 37.9 W, P = 0.002), and changes in average work output at 70% HRmax correlated with changes in exercise time to elicit 70% HRmax (r = 0.87, P < 0.001) as well as changes in VO2 at 70% HRmax (r = 0.75, P < 0.001). Thus, the AAT appears to be a valid measure of submaximal work capacity. CONCLUSIONS: The AAT is a reproducible and valid measure of submaximal work capacity that can serve as an effective means to evaluate physical activity interventions.

Adaptation, Physiological↗

PubMed1998

Reproducibility of a solid and of a liquid caloric meal for gastric emptying studies.

Simple meals are required for routine scintigraphic gastric emptying studies. We evaluated the reproducibility of a caloric liquid meal (520 kcal) compared to that of a solid meal (638 kcal) in 8 and 11 healthy volunteers, respectively. Gastric emptying rates and half-times were similar in two tests using the same meal, while the methods used to express lag times were not highly reproducible. The emptying rates and half-times of the liquid meal were delayed after the intake of bellafoline. In conclusion, this study demonstrates that: (a) gastric emptying rates and half-times are reproducible parameters for the expression of scintigraphic gastric emptying studies; (b) mathematical methods to express lag times are not highly reproducible; (c) a 500 kcal liquid meal is sensitive to the effects of bellafoline, a drug able to delay gastric emptying. Further clinical evaluation is required to test its applicability in routine studies.

Adult↗

PubMed2000

Reproducibility and repeatability of 99Tcm-HMPAO rCBF SPET in normal subjects at rest using brain atlas matching.

The aim of this study was to assess regional cerebral blood flow (rCBF) in normal subjects at rest using 99Tcm-HMPAO single photon emission tomography (SPET). Analysis of reproducibility and repeatability was performed both before and after normalization of flow data. Six healthy volunteers were examined, three times each, according to a routine rCBF protocol. A computerized brain atlas was used to evaluate flow data in eight selected regions. The overall reproducibility of rCBF was evaluated from two scans performed at an average interval of 3 months. Repeatability was evaluated from two scans, 3 h apart and without re-injection of 99Tcm-HMPAO. For the normalized (relative) flow data, the reproducibility was +/- 1.3% and the repeatability +/- 2.2% (i.e. methodological errors dominate). For the non-normalized flow data, the corresponding values were +/- 14.8% and +/- 5.9%. rCBF SPET with 99Tcm-HMPAO is highly reproducible provided that the flow data are normalized. The variation in flow between individuals at one point in time and 3 months later was less than +/- 5% for all brain regions.

Adult↗

PubMed2001

Interpretive intra- and interobserver reproducibility of rest/stress 99Tcm-sestamibi myocardial perfusion SPECT in a consecutive group of male patients with stable angina pectoris before and after percutaneous transluminal angioplasty.

BACKGROUND: Observer variability of 99Tcm-sestamibi myocardial perfusion imaging (MPI) has rarely been investigated. The aim of our study was to evaluate the interpretive reproducibility with this technique. PATIENTS: We report on 108 consecutive male patients with stable angina pectoris, investigated before and after percutaneous transluminal angioplasty (PTCA). METHODS: A 2-day rest/stress 99Tcm-sestamibi gated single photon emission computed tomography (SPECT) protocol was used. MPI was interpreted by two independent observers without knowledge of clinical data, using a 20-segment scoring model. RESULTS: Intra- and interobserver agreement was found to be good to excellent (kappa = 0.71-0.85) with regard to the overall diagnosis as well as the individual vessel diagnosis (kappa = 0.60-0.87). However, agreement was higher for left anterior descending coronary artery (LAD) and left circumflex coronary artery (LCX) vascular territories than for the right coronary artery (RCA) territory. Moderate to good intraobserver agreement (kappa = 00.54-0.68) and slightly lower interobserver agreement (kappa = 0.52-0.56) was found for segmental score interpretation. When comparing the interpretive reproducibility before and after PTCA intra- and interobserver agreement was better after PTCA, probably reflecting the increase in normal scans after revascularization. CONCLUSIONS: In a group of consecutive male patients with stable angina pectoris interpretive reproducibility (overall and individual vessel diagnosis) was good to excellent. However, segmental scoring reproducibility was moderate to good.

Adult↗

PubMedDate not supplied

Reproducibility of mental stress-induced myocardial ischemia in the Psychophysiological Investigations of Myocardial Ischemia (PIMI).

OBJECTIVE: Many patients with coronary artery disease (CAD) develop myocardial ischemia in response to mental stress. This has been documented both in the natural environment and in the laboratory. However, the reproducibility of laboratory mental stress-induced ischemia has not been investigated. METHOD: Sixty patients with documented CAD and a positive exercise stress test discontinued cardiac medications and underwent two standardized mental stress tests (a timed Stroop Color-Word test and a public speaking task) in a nuclear cardiology laboratory (Visit 1), and repeated this procedure between 2 and 8 weeks later (Visit 2). Measurements of cardiovascular function and neurohormonal responses were obtained throughout testing, and mood state was assessed before and after testing. RESULTS: Sixty-eight percent of the 56 patients with detailed radionuclide data from both visits had consistent responses (ie, ischemia either present during both sessions or absent during both) to the Stroop task (kappa = .29, p = .03), 61% had consistent responses to the speech task (kappa = .20, p = .12), and 60% had consistent responses when ischemia was considered present if it occurred during either the Stroop test, the speech task, or both, and absent if it did not occur during either task (kappa = .22, p = .07). Hemodynamic and neuroendocrine responses to the tests were moderately reproducible. CONCLUSIONS: We conclude that two popular laboratory tests for mental stress-induced myocardial ischemia are modestly reproducible. The relatively low reproducibility is probably influenced by uncertainties in detecting relatively small changes in wall motion, habituation of the patient to repeated exposure to psychological stressors, and physiological differences in threshold for ischemia on different days of testing.

Adult↗

PubMed1999

Factors in the reproducibility of electromyographic power spectrum analysis of lumbar paraspinal muscle fatigue.

STUDY DESIGN: An investigation of the reliability of various factors used to analyze electromyograms of paraspinal muscles of the lumbar spine. OBJECTIVES: To determine the reproducibility of several electromyographic variables over time and to assess the influence of confounding factors. SUMMARY OF BACKGROUND DATA: Previous reliability studies have included small numbers of subjects and often have not explored the factors that can influence the reliability of this technique. METHODS: In the first study, 39 volunteers underwent electromyographic tests on three occasions at two loads. The time interval was 1 week between tests. Electromyographic variables measured included half-width (spectral width at half maximum amplitude), initial median frequency, median frequency slope, initial root mean square, root mean square, and root mean square slope. In the second study to determine the influence of posture, nine volunteers were tested on two occasions with a change in posture between tests. RESULTS: Reliability was better for tests at the higher loads. Initial median frequency, half-width, and root mean square all had acceptable reproducibility over time, with a coefficient of variation less than 10. Initial median frequency and half-width proved to be the most suitable variables; they yielded the largest between-subject variation and, of all variables, were affected the least by changes in load. The remaining variables were very load-dependent. A change in posture greatly influenced the reproducibility. CONCLUSION: These results demonstrate that only initial median frequency and half-width have acceptable reproducibility over time and at different loads, with the potential to be useful in discriminating between individuals. Changes in posture can greatly change an electromyographic result.

Adult↗

PubMed2006

Short-term reproducibility of a non-dipping pattern in type 2 diabetic hypertensive patients.

BACKGROUND: Little information is available on the reproducibility of nocturnal variations in blood pressure in type 2 diabetic hypertensive patients. OBJECTIVE: We aimed to compare the intrasubject short-term reproducibility of a nocturnal non-dipping pattern and the prevalence of cardiac and extracardiac signs of target organ damage, in a group of type 2 diabetic hypertensive patients and in an age/gender-matched group of non-diabetic hypertensive subjects. METHODS: Thirty-six treated hypertensive patients with long-lasting type 2 diabetes (> 10 years duration) consecutively attending our hospital out-patient hypertension clinic (group I; mean age, 65 +/- 9 years), and 61 untreated non-diabetic subjects with grade 1 and grade 2 uncomplicated essential hypertension, matched for age and gender, and chosen from patients attending an outpatient clinic (group II; mean age, 65 +/- 5 years), were considered for this analysis. All patients underwent blood sampling for routine blood chemistry, 24-h urine collection for microalbuminuria, two 24-h periods of ambulatory blood pressure monitoring (ABPM) within a 4-week period, echocardiography, and carotid ultrasonography. A dipping pattern was defined as a greater than 10% reduction in the average systolic and diastolic blood pressure at night compared with average daytime values. RESULTS: A reproducible nocturnal dipping and non-dipping profile was found in 11 (30.6%) and 21 (58.3%) diabetic patients, respectively; while only in four (11.1%) patients was a variable dipping profile observed. Of the 23 patients with a non-dipping pattern during the first ABPM period, 21 (91.3%) also had this type of pattern during the second ABPM recording. In group II (non-diabetic hypertensive patients), 30 patients (49.2%, P < 0.05) had a dipping pattern, 13 patients (21.3%, P < 0.01) had a non-dipping profile pattern and 18 patients (29.5%, P < 0.01) had a variable dipping pattern. Of the 20 patients with a non-dipping pattern during the first ABPM period, 13 (65.0%) confirmed this type of pattern during the second ABPM recording. Finally, the prevalence of left ventricular hypertrophy (77.7 versus 41.4%, P < 0.01), carotid plaques (80.5 versus 38.3%, P < 0.01), carotid intima-media thickening (54.3 versus 44.0%, P < 0.05) and microalbuminuria (11.1 versus 2.0%, P < 0.01) was significantly higher in group I than in group II. According to a logistic regression analysis, diabetes, left ventricular hypertrophy and carotid plaques were the main independent predictors of the non-dipping (pattern in the overall population. CONCLUSIONS: These findings indicate that intrasubject variability of non-dipper pattern is lower in diabetic than in non-diabetic hypertensive patients, that classification of diabetic hypertensive patients as dipper or non-dipper on the basis of a single ABP recording is more reliable than in non-diabetic patients, and that the more frequent and reproducible non-dipping (pattern in diabetic patients is associated with a more prominent cardiac and extracardiac target organ damage.

Aged↗

PubMed2005

The reproducibility of dipping status: beyond the cutoff points.

A limited reproducibility has been ascribed to 24-h ambulatory blood pressure monitoring, especially in relation to the dipper and nondipper phenomena. This study examined the reproducibility of 24-h ambulatory blood pressure monitoring in three recordings of pressure at intervals of 8-15 days in 101 study participants (73% treated hypertensive patients) residing in the city of Recife, Pernambuco, Brazil. SpaceLabs 90207 monitors were used, and the minimum number of valid measurements was 80. No significant differences were found between the mean systolic and diastolic pressures, between the second and third recordings when the normotensive and hypertensive patients were assessed jointly (P=0.44). Likewise, no significant differences were present when the normotensive patients were analyzed separately (P=0.96). In the hypertensive group, a significant difference existed between only the first and second ambulatory blood pressure readings (135.1 vs. 132.9 mmHg, respectively; P=0.0005). Regarding declines in pressure during sleep, no significant differences occurred when continuous percentage values were considered (P=0.27). The values obtained from 24-h ambulatory blood pressure monitoring are reproducible when tested at intervals of 8-15 days. Small differences, when significantly present, always involved the first ambulatory blood pressure monitoring. The reproducibility of the dipper and nondipper patterns is of greater complexity because it considers cutoff points rather than continuous ones to characterize these states.

Adult↗

PubMed2006

Reproducibility of technetium-99m mercaptoacetyltriglycine clearance in patients with impaired renal function.

BACKGROUND: The aim of this study was to determine the reproducibility of technetium-99m mercaptoacetyltriglycine (99mTc-MAG3) clearance in patients with a 99mTc-MAG3 clearance below 100 ml/min/1.73 m2. METHODS: Two separate multi-sample clearance studies were performed in 16 patients at a 1 week interval. The clearances were calculated according to the open two-compartment model of Sapirstein et al., accepting the 90, 120 and 180 min samples as the last points of the biexponential curve. The clearance measurements were also performed according to the single-sample methods of Russell et al. and Bubeck using the fitted value at 44 min. RESULTS: There was no significant difference between the two clearance measurements for all five samples (P>0.05). There was a systematic increase in clearance measurements of 8.0+/-2.7% from the 180 to 120 min samples and 4.8+/-2.0% from the 120 to 90 min samples. Both single-sample methods (Bubeck and Russell et al.) gave more divergent results than multi-sample methods. The mean and standard deviation (%) of the normalized differences between two successive tests were -3.9+/-12.6, -2.4+/-13.1, -1.9+/-14.9, -4.1+/-53.5 and -13+/-82.1 for 90, 120 and 180 min samples and the Russell et al. and Bubeck methods, respectively. CONCLUSION: Single-sample methods give very poor reproducibility and accuracy and should not be used in patients with poor renal function. The reproducibility of 99mTc-MAG3 clearance using the multi-sample method (90 min) in patients with impaired renal function is 12.6%, which is similar to that in patients with good renal function and that obtained with other tubular agents. Whether this level of reproducibility is satisfactory for documenting serial changes in an individual patient with a 99mTc-MAG3 clearance below 100 ml/min/1.73 m2 depends on the expectation of the clinician.

Adult↗

PubMed2003

Prognostic value and reproducibility of koilocytosis in cervical intraepithelial neoplasia.

The purpose of this study was to evaluate the influence of koilocytosis on the progression of cervical intraepithelial neoplasia (CIN) to a higher grade during follow-up in cervical biopsy specimens with CIN 1 and 2. In adequate, consecutive, biopsy specimens of 103 CIN 1 and 2 patients, CIN grade and presence or absence of koilocytosis were assessed. Patients were followed by colposcopy and cytology according to protocol. When recurrent CIN was suspected with either of the techniques, a re-biopsy was taken. Progression of the CIN was defined as an increase of grade by at least 1. Univariate analysis was applied to all patients and in the CIN 1 and 2 subgroups separately. An experienced gynecological pathologist using strict criteria reviewed koilocytosis. The Kappa test was used to assess interobserver reproducibility of koilocytosis. Koilocytosis was found in 70 (68%) of the specimens (18 of 29=62% of the CIN 1 and 52 of 74=70% of the CIN 2 cases). Twenty-one of 103 (20%) dysplasias progressed and 10 of these (48%) showed koilocytosis. Koilocytosis was found more frequently (73%, 60 of 82) in the cases that showed no progression. Follow-up showed that patients with koilocytosis had a significantly lower likelihood of progression (log-rank=5.5, p=0.02). In CIN 1, progression without and with koilocytosis was 27% and 0%, respectively, log-rank=4.9, p=0.03. In CIN 2, a similar trend was found: only 10 of 52 (19%) CIN 2 cases with koilocytosis progressed, whereas 8 of 22 (36%) lesions lacking koilocytosis progressed, a difference just below significance (p=0.06). In agreement with other studies, interobserver diagnosis of koilocytosis was poorly reproducible. In conclusion, the presence of koilocytosis is associated with a lack of progression in CIN 1 lesions, but reproducibility of koilocytosis assessment is not optimal. Therefore, other more objective and better reproducible criteria are required to extract the potentially important prognostic information contained in the microscopic image of CIN 1 and 2 lesions.

Analysis of Variance↗

PubMed2006

Reproducibility of a scoring system for computed tomography scanning in cystic fibrosis.

INTRODUCTION: Computerized tomography (CT) scanning shows promise as an outcome surrogate for cystic fibrosis (CF) lung disease progression. The scoring system used to convert the CT image to numeric data is an essential determinant of the performance of CT scanning. METHODS: Three radiologists independently scored 16 high-resolution CT scans performed on children in the Wisconsin CF Neonatal Screening Project. The test scans were selected to provide a broad range of disease severity. The scoring system provided subscores for the presence and severity of 5 findings of CF lung disease. The sum of the subscores provided a total score. The CT scans were then read again by each of the radiologists at least 11 months later. Using Mixed Effects Linear Model Analysis, the sources of error (scan-to-scan variation, interrater variance, and intrarater variance) were calculated. RESULTS: For the total score, the scan-to-scan variation was 14.48, interrater variance was 0.28, and intrarater variance was 0.45, with an overall reproducibility of 95%. The square root of scan-to-scan variance, a measure of sensitivity, was 3.81. Evaluation of the subscores showed higher reproducibility for bronchiectasis and hyperinflation (95% and 88%, respectively). The bronchiectasis score was more sensitive than the air-trapping score (1.46 vs. 0.89). DISCUSSION: This system was developed to provide a reproducible method that could be used to evaluate the lobar location, severity, and extent of a broad spectrum of CT features of CF lung disease, especially in children. This study demonstrates that the overall score is both sensitive to variation in the severity of lung disease and reproducible.

Adolescent↗

PubMed1996

Sensitivity, reproducibility, and accuracy in short tandem repeat genotyping using capillary array electrophoresis.

The Human Genome Initiative has increased significantly the rate at which disease-causing genes are being mapped and sequenced. New cost-effective methods to locate the genes and to characterize disease-causing mutations require robust, reproducible, and accurate protocols for measuring DNA fragment lengths. Capillary array electrophoresis (CAE) offers rapid, high-resolution separations, high throughput, and sensitive detection. To assess the utility of CAE for the accumulation of genetic information, we tested both sizing accuracy and reproducibility using 48-capillary prototype systems. Two multiplex PCR allelic ladder standards and several CA-repeat markers were analyzed in > 100 runs. Reproducibility in typing > 8000 genotypes reveals a standard deviation of less than 0.2 bp on these systems under optimized conditions. However, sequence-dependent migration anomalies were observed at most simple sequence loci even when analyzed under denaturing conditions, resulting in a systematic bias in estimated fragment sizes. We show here that, by normalizing results to known typing controls, one can obtain locus-averaged accuracies of < 0.06 bp and normalized results within 1 bp of actual. We detect as little as a 1:30,000 dilution of a DNA quantitation standard stained with highly sensitive intercalating dyes, indicating an 80-zeptomole sensitivity limit. However, to obtain reproducible electrokinetic injection, approximately 200 attomoles of fluorescein-labeled DNA is required. These sensitivity limits, sizing precision, and accuracy, together with the 1-hr run times for 48-96 samples, indicate that CAE is a viable method for high-throughput genetic analysis of simple sequence repeat polymorphisms.

Capillary Action↗