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[Reproducibility of dynamic contour tonometry. Comparison with TonoPenXL and Goldmann applanation tonometry - a clinical study on 323 normal eyes].

BACKGROUND: The PASCAL Dynamic Contour Tonometer (DCT) is a new diagnostic approach for the digital measurement of intraocular pressure (IOP) in eyes with glaucoma. The aim of this study was to evaluate the reproducibility of DCT in normal eyes and to compare DCT with Goldmann applanation tonometry (GAT) and TonoPenXL. PATIENTS AND METHODS: A prospective cross-sectional study on 323 normal, consecutive eyes was performed. Eyes with an IOP of more than 23 mmHg (GAT) were excluded. Central corneal power (Zeiss Ophthalmometer) and central corneal thickness (ultrasound pachymetry: Tomey AL-1000) were taken. The IOP readings were obtained as follows: 3 x DCT [quality of measurement, IOP and ocular pulse amplitude (OPA) were taken], 1 x TonoPenXL, GAT, finally: once again DCT to evaluate the tonography effect. RESULTS: The quality of 3 following IOP (DCT) readings was good (quality Q1 = 43.4 %, Q2 = 32.5 %, Q3 = 22.7 %). The reproducibility of the IOP (DCT) measurements was excellent (first measurement IOP (DCT) = 18.1 +/- 3.4 mmHg, second measurement IOP (DCT) = 18.1 +/- 3.4 mmHg, third measurement IOP (DCT) = 17.8 +/- 3.4 mmHg, Cronbach's alpha = 0.976). First and second IOP (DCT) values showed a strong correlation (r = 0.93). A significant tonography effect was observed between first and third IOP (DCT) measurements (0.4 mmHg; p = 0.004). Mean OPA (DCT) was 3.0 mmHg during the first three measurements (Cronbach's alpha = 0.964). IOP (DCT) and OPA (DCT) reproducibility showed no laterality. IOP (DCT) (17.7 +/- 3.4 mmHg) was significantly higher than IOP (TonoPenXL) (16.0 +/- 3.2 mmHg, n = 275; p < 0.001) and higher than IOP (GAT) (14.5 +/- 3.1 mmHg, n = 275; p < 0.001). The effect of tonography between the third and last IOP (DCT) measurement was zero (p = 0.6). IOP (DCT) and IOP (GAT) values were only weak correlated with central corneal thickness. CONCLUSIONS: IOP and OPA values measured with the DCT are extraordinary reproducible in normal eyes. Frequently, DCT detects higher IOP values than those obtained with TonoPenXL and GAT. A reproducible measurement of IOP and OPA may open new diagnostic fields, e. g., in glaucoma detection or ocular vascular diseases.

Cross-Over Studies↗

Reproducibility of growth hormone and cortisol responses to the insulin tolerance test and the short ACTH test in normal adults.

Previous studies have demonstrated poor reproducibility of growth hormone (GH) responses to insulin tolerance testing (ITT). In order to investigate whether this is a particular feature of GH secretion we studied the reproducibility of the GH and cortisol responses to ITT simultaneously and also compared the latter with the reproducibility during short ACTH testing (SAT). Eight normal men (age 26-50) and 8 normal women (age 27-45) underwent 2 ITT and 2 SAT. In the ITT no systematic differences were observed between test 1 and 2 concerning blood glucose, GH and cortisol before and after stimulation. Similar results were obtained for cortisol during SAT. During ITT reproducibility was good for the cortisol response (coefficient of variation [CV] 10%, no sex differences) but poor for the GH response (CV 41% in men, 104% in women). Reproducibility was good for the cortisol response in SAT (CV 12%, no sex differences). The peak cortisol values during ITT (mean 585, range 448-775 nmol/l) were significantly lower than in the 2 SAT (mean 723, range 486-918 nmol/l). We conclude that the GH response during testing is more variable than the cortisol response. This could account for some of the difficulties encountered in the diagnosis of GH deficiency in adults.

Adrenocorticotropic Hormone↗

Synaptic input statistics tune the variability and reproducibility of neuronal responses.

Synaptic waveforms, constructed from excitatory and inhibitory presynaptic Poisson trains, are presented to living and computational neurons. We review how the average output of a neuron (e.g., the firing rate) is set by the difference between excitatory and inhibitory event rates while neuronal variability is set by their sum. We distinguish neuronal variability from reproducibility. Variability quantifies how much an output measure is expected to vary; for example, the interspike interval coefficient of variation quantifies the typical range of interspike intervals. Reproducibility quantifies the similarity of neuronal outputs in response to repeated presentations of identical stimuli. Although variability and reproducibility are conceptually distinct, we show that, for ideal current source synapses, reproducibility is defined entirely by variability. For physiologically realistic conductance-based synapses, however, reproducibility is distinct from variability and average output, set by the Poisson rate and the degree of synchrony within the synaptic waveform.

Action Potentials↗

Detection and reproducibility of mental stress-induced myocardial ischemia with Tc-99m sestamibi SPECT in normal and coronary artery disease populations.

BACKGROUND: Mental stress-induced ischemia, as detected by radionuclide studies, has yielded reversible ischemia in only 30% to 60% of patients with exercise-induced ischemia. Little is known about the reproducibility of myocardial perfusion imaging in detecting mental stress-induced ischemia. The purpose of this study was to further evaluate the occurrence and reproducibility of mental stress-induced ischemia in patients with coronary artery disease (CAD) and in normal control subjects with a low likelihood of CAD by using sestamibi single photon emission computed tomography (SPECT) imaging. METHODS AND RESULTS: A total of 40 patients were enrolled in this study: 19 patients with CAD and typical angina or reversible ischemia (positive exercise treadmill study or positive adenosine thallium study) and 21 normal control subjects underwent mental stress testing as well as myocardial perfusion imaging. The subjects were given a speaking task, and SPECT imaging was subsequently performed. Two experienced readers compared mental stress imaging with a resting image using a 20-segment cardiac model. Hemodynamic changes in blood pressure and heart rate with mental stress were also measured in all subjects. Each patient with CAD also underwent repeat mental stress testing and myocardial imaging approximately 2 weeks later. Of the 19 patients with CAD and typical angina or with evidence of reversible ischemia, 16 (84%) demonstrated ischemia with mental stress, as detected by sestamibi SPECT imaging. The mean number of new or worsened perfusion defects attributable to mental stress was 3.5, with a mean severity of 1.7. These results were also reproducible. With repeated mental stress testing and myocardial imaging, 12 of the 16 CAD patients (75%) demonstrated evidence of myocardial ischemia. None of the 21 normal control subjects had evidence of mental stress-induced myocardial ischemia. Mental stress also induced reproducible and significant hemodynamic changes in CAD patients. CONCLUSIONS: In patients with known CAD with typical angina or with evidence of reversible ischemia despite taking medications, mental stress was very effective in inducing myocardial ischemia, as detected by sestamibi SPECT imaging. Mental stress was also found to elicit significant hemodynamic responses. Furthermore, these findings demonstrated good reproducibility.

Adult↗

Reproducibility of ultrasound scan in the assessment of volume flow in the veins of the lower extremities.

PURPOSE: The purpose of this study was the identification of the optimal settings of ultrasound scan flow measurement in the veins and the determination of whether the standardization of these settings can provide acceptable reproducibility of the venous flow measurements in individual segments of the lower extremity veins. METHODS: The venous cross-sectional area, the time average mean velocity, and the venous volume flow of 25 healthy volunteers were examined with duplex ultrasound scanning. Reproducibility was examined with different measurement settings. Doppler scan sample volume size, ultrasound scan beam incident angle, and time interval of measurement were varied across a spectrum for arrival at the setting for highest reproducibility of the flow volume measurements. Test-retest reproducibility of venous flow volume measurements then was investigated with optimized settings. RESULTS: The highest repeatability of volume flow measurements was achieved when the full lumen of the vein was insonated (coefficient of repeatability [CR] = 1.88 cm/s), the ultrasound scan beam incident angle was equal to 60 degrees (CR = 1.56 cm/s), and the measurement time was more than 40 seconds (CR = 1.64 cm/s). The mean values of volume flow were 360 mL/min in the common femoral vein, 147 mL/min in the superficial femoral vein, 86 mL/min in the profunda femoral vein, and 38 mL/min in the greater saphenous vein. Test-retest repeatability coefficients were 96.9 mL/min for the common femoral vein, 70.2 mL/min for the superficial femoral vein, 40.8 mL/min for the profunda femoral vein, and 16.8 mL/min for the greater saphenous vein. CONCLUSION: The reproducibility of ultrasound scan measurements of volume flow in veins is optimized with the use of sampling volumes that cover the entire venous lumen, with an incident angle of 60 degrees and measuring for 40-second intervals or longer. With these defined variables, volumetric measurements are sufficiently repeatable. the values of flow volume measured with duplex ultrasound scanning were comparable to those with thermodilution techniques that were reported previously.

Blood Flow Velocity↗

Reproducibility of a short semi-quantitative food group questionnaire and its performance in estimating nutrient intake compared with a 7-day diet diary in the Million Women Study.

OBJECTIVES: To assess the short- and long-term reproducibility of a short food group questionnaire, and to compare its performance for estimating nutrient intakes in comparison with a 7-day diet diary. DESIGN: Participants for the reproducibility study completed the food group questionnaire at two time points, up to 2 years apart. Participants for the performance study completed both the food group questionnaire and a 7-day diet diary a few months apart. Reproducibility was assessed by kappa statistics and percentage change between the two questionnaires; performance was assessed by kappa statistics, rank correlations and percentages of participants classified into the same and opposite thirds of intake. SETTING: A random sample of participants in the Million Women Study, a population-based prospective study in the UK. SUBJECTS: In total, 12 221 women aged 50-64 years. RESULTS: In the reproducibility study, 75% of the food group items showed at least moderate agreement for all four time-point comparisons. Items showing fair agreement or worse tended to be those where few respondents reported eating them more than once a week, those consumed in small amounts and those relating to types of fat consumed. Compared with the diet diary, the food group questionnaire showed consistently reasonable performance for the nutrients carbohydrate, saturated fat, cholesterol, total sugars, alcohol, fibre, calcium, riboflavin, folate and vitamin C. CONCLUSIONS: The short food group questionnaire used in this study has been shown to be reproducible over time and to perform reasonably well for the assessment of a number of dietary nutrients.

Cross-Sectional Studies↗

Reproducibility of body temperature response to standardized test conditions when assessing clothing.

The traditional use of core temperature to assess the thermal effects of clothing has recently been questioned. The purpose of this study was to assess the reproducibility of body temperature in five subjects (mean age, 22.6 +/- 1.5 years) wearing either athletic clothing or a chemical protective overgarment while exercising at 20 degrees C and at 40 degrees C. The exercise was preceded by a 1 h adaptation period in a controlled environmental chamber. Results indicated that mean group change in rectal temperature (delta Tr) appeared to be reproducible for both garment ensembles at 20 degrees C but not at 40 degrees C. For mean change in oesophageal temperature (delta T(oes)) at 20 degrees C, reproducibility was obtained for the overgarment but not for the athletic garment; at 40 degrees C, mean delta T(oes) appeared to be reproducible with both garments. However, when individual responses were examined, there was little reproducibility for either delta Tr or delta T(oes). In addition, these measurements failed to show differences in the types of clothing worn. It was concluded that the use of core temperature to assess heat stress imposed by wearing clothing during exercise may lead to erroneous conclusions.

Adult↗

Reproducibility of survey results from a study of occupation-related respiratory health in the aluminum industry.

Confidence in dose-response relationships arising from occupational studies is dependent upon the reliability and validity of relevant exposure and morbidity estimates. Often self-reported occupational histories are a surrogate for direct exposure measures, and self-report of symptoms serves a similar purpose in place of more objective measures of morbidity. Unfortunately, there are few methods for validating either of these sources of information. This study attempts to evaluate the reproducibility of a survey instrument, and resulting cumulative exposure estimates, utilized in a study of work-related respiratory morbidity in the aluminum industry. The survey instrument comprised measures of pulmonary function, atopic status, smoking, occupational history, and respiratory symptoms. A Task Exposure Matrix was used to estimate exposure categories and cumulative exposure scores. Two groups of employees were administered the survey instrument on two separate occasions. Group A (n = 74) completed their two surveys more than ten weeks apart and Group B (n = 43) completed their surveys less than two weeks apart. Reproducibility was assessed using Cohen's Kappa for categorically measured outcome measures and intraclass correlation coefficients for continuously measured outcomes. Agreement across most variables, for both groups, was generally high. Repeatability of self-reported respiratory symptoms ranged from 70 to 98 percent (Group A) and 88 to 100 percent (Group B). Cumulative exposure scores were highly reproducible, despite some discrepancies in the self-reported occupational histories across interviews, with most of the calculated intraclass r scores exceeding 0.8. These results give strength to studies reporting dose-response relationships derived from similarly collected data. Reproducibility of the survey data was enhanced by use of standardized questionnaire material, consistent interview structure, and calibrated equipment for objective observation. In particular the authors recommend use of a company job dictionary to optimize reproducibility of self-reported occupational information.

Adult↗

Multiple steps of phosphorylation of activated rhodopsin can account for the reproducibility of vertebrate rod single-photon responses.

Single-photon responses (SPRs) in vertebrate rods are considerably less variable than expected if isomerized rhodopsin (R*) inactivated in a single, memoryless step, and no other variability-reducing mechanisms were available. We present a new stochastic model, the core of which is the successive ratcheting down of R* activity, and a concomitant increase in the probability of quenching of R* by arrestin (Arr), with each phosphorylation of R* (Gibson, S.K., J.H. Parkes, and P.A. Liebman. 2000. Biochemistry. 39:5738-5749.). We evaluated the model by means of Monte-Carlo simulations of dim-flash responses, and compared the response statistics derived from them with those obtained from empirical dim-flash data (Whitlock, G.G., and T.D. Lamb. 1999. Neuron. 23:337-351.). The model accounts for four quantitative measures of SPR reproducibility. It also reproduces qualitative features of rod responses obtained with altered nucleotide levels, and thus contradicts the conclusion that such responses imply that phosphorylation cannot dominate R* inactivation (Rieke, F., and D.A. Baylor. 1998a. Biophys. J. 75:1836-1857; Field, G.D., and F. Rieke. 2002. Neuron. 35:733-747.). Moreover, the model is able to reproduce the salient qualitative features of SPRs obtained from mouse rods that had been genetically modified with specific pathways of R* inactivation or Ca2+ feedback disabled. We present a theoretical analysis showing that the variability of the area under the SPR estimates the variability of integrated R* activity, and can provide a valid gauge of the number of R* inactivation steps. We show that there is a heretofore unappreciated tradeoff between variability of SPR amplitude and SPR duration that depends critically on the kinetics of inactivation of R* relative to the net kinetics of the downstream reactions in the cascade. Because of this dependence, neither the variability of SPR amplitude nor duration provides a reliable estimate of the underlying variability of integrated R* activity, and cannot be used to estimate the minimum number of R* inactivation steps. We conclude that multiple phosphorylation-dependent decrements in R* activity (with Arr-quench) can confer the observed reproducibility of rod SPRs; there is no compelling need to invoke a long series of non-phosphorylation dependent state changes in R* (as in Rieke, F., and D.A. Baylor. 1998a. Biophys. J. 75:1836-1857; Field, G.D., and F. Rieke. 2002. Neuron. 35:733-747.). Our analyses, plus data and modeling of others (Rieke, F., and D.A. Baylor. 1998a. Biophys. J. 75:1836-1857; Field, G.D., and F. Rieke. 2002. Neuron. 35:733-747.), also argue strongly against either feedback (including Ca2+-feedback) or depletion of any molecular species downstream to R* as the dominant cause of SPR reproducibility.

Adenosine Triphosphate↗

Reproducibility of electrical impedance tomographic spectroscopy (EITS) parametric images of neonatal lungs.

The reproducibility of electrical impedance tomographic spectroscopy (EITS) images of neonatal lungs have been investigated in 11 clinically stable babies. We have used the Sheffield Mark IIIa EITS system. An average inspiration frame was generated from the data frames associated with maximum inspiration. Frequency images were reconstructed from these frames. The frequency images were analysed to locate the pixel with the maximum change in the right lung field. The change was defined as the 614 kHz measurement relative to 9.6 kHz. A 3 x 3 pixel region of interest was centred at this point. The changes in impedance with frequency for this region of interest show good overall reproducibility between electrode applications for eight frequencies (95% limits of agreement +/- 28%). This reproducibility is improved (95% limits of agreement +/- 13%) by omitting the highest frequency (1.2 MHz) which is most subject to system noise. The parameters for the Cole model derived from data with the highest frequency omitted are less reproducible between electrode applications (95% limits of agreement, R/S +/- 0.83, fc +/- 81.6, RC +/- 0.52, SC +/- 0.39). We suspect that the parametric model used may have an effect on this. The signals recorded at the highest frequency (1.2 MHz) are a major source of variability. The reproducibility results are improved by omitting this frequency from the analysis.

Body Water↗

A reproducible laser-wounded skin equivalent model to study the effects of aging in vitro.

Skin aging involves both chronological and photoaging processes. The effects of these processes are often overlapping and include changes in both the stratified epithelium and the fibroblast-rich dermis. Wound healing is frequently delayed with aging and can result in scarring. A skin equivalent model can be used to study the role of cells and the extracellular matrix in the process of wound healing. Current studies using this model employ a full-thickness wound placed atop a nonwounded dermis to mimic a partial-thickness wound. However, a true reproducible partial-thickness wound model has yet to be described. In this study, we investigated whether a laser-wounded skin equivalent would be a useful partial-thickness wound healing model. Three lasers were compared for the ability to generate a reproducible wound: an erbium-YAG, a high-powered excimer, and a low-powered excimer laser. Reepithelialization ability was tested using newborn and adult skin keratinocytes, adult esophageal keratinocytes, and cdk4-overexpressing newborn keratinocytes. Keratinocyte compartmentalization and basement membrane formation were assessed by immunofluorescence. The erbium-YAG and high-powered excimer laser cut reproducible wounds but left the remaining surface either discolored due to thermal damage and/or ragged; keratinocytes were unable to migrate into the wound area. The low-powered excimer laser cut reproducible wounds, leaving the cut surface intact and visibly unaltered; keratinocytes reepithelialized the wound in a collagenase-dependent manner within 3 days; and return of compartmentalization and basement membrane occurred within 14 days. The laser-wounded skin equivalent is an adjustable, reproducible partial-thickness wound model where keratinocyte biology akin to in vivo can be studied, and will be useful to study the effects of aging on wound healing.

Basement Membrane↗

Reproducibility of intraocular pressure and outflow facility measured by pneumatic tonography and Schiotz tonography.

The purpose of this study was to compare means, variability, and reproducibility in intraocular pressure and in outflow facility measured repeatedly over several days by Bio-Rad pneumatonography and Schiotz tonography in normal human volunteers. For each instrument a measurement of intraocular pressure and one of outflow facility were obtained at each of three repeated examinations of eight healthy subjects in the supine position. For pressure, the Bio-Rad mean was significantly higher by 5.31 mmHg than the Schiotz mean (p < 0.00005). Reproducibility was 71.1% and 59.0% for the Bio-Rad and Schiotz, respectively. For outflow, the Bio-Rad and Schiotz means were not significantly different. Reproducibility was 17.3% and 58.7% for the Bio-Rad and Schiotz, respectively. For measuring pressure, both the Bio-Rad and Schiotz instruments had good reproducibility; for measuring outflow, the Bio-Rad and Schiotz instruments had low and good reproducibility, respectively.

Adult↗

Reproducibility and validity of the Shanghai Women's Health Study physical activity questionnaire.

In this investigation, the authors evaluated the reproducibility and validity of the Shanghai Women's Health Study (SWHS) physical activity questionnaire (PAQ), which was administered in a cohort study of approximately 75,000 Chinese women aged 40-70 years. Reproducibility (2-year test-retest) was evaluated using kappa statistics and intraclass correlation coefficients (ICCs). Validity was evaluated by comparing Spearman correlations (r) for the SWHS PAQ with two criterion measures administered over a period of 12 months: four 7-day physical activity logs and up to 28 7-day PAQs. Women were recruited from the SWHS cohort (n = 200). Results indicated that the reproducibility of adolescent and adult exercise participation (kappa = 0.85 and kappa = 0.64, respectively) and years of adolescent exercise and adult exercise energy expenditure (ICC = 0.83 and ICC = 0.70, respectively) was reasonable. Reproducibility values for adult lifestyle activities were lower (ICC = 0.14-0.54). Significant correlations between the PAQ and criterion measures of adult exercise were observed for the first PAQ administration (physical activity log, r = 0.50; 7-day PAQ, r = 0.62) and the second PAQ administration (physical activity log, r = 0.74; 7-day PAQ, r = 0.80). Significant correlations between PAQ lifestyle activities and the 7-day PAQ were also noted (r = 0.33-0.88). These data indicate that the SWHS PAQ is a reproducible and valid measure of exercise behaviors and that it demonstrates utility in stratifying women by levels of important lifestyle activities (e.g., housework, walking, cycling).

Adolescent↗

Reproducibility and validity of major dietary patterns among Swedish women assessed with a food-frequency questionnaire.

Defining dietary patterns by factor analysis is an alternative approach to dietary assessment that has been used recently to examine diet-disease relations. However, only 1 study evaluated the reproducibility and validity of this method. Our aim was to assess both the validity and reproducibility of major dietary patterns based on data from a 60-item FFQ. We chose 2 independent random samples among over 60,000 women aged 40-74 y participating in the Swedish Mammography Cohort (SMC). In the validation study, the FFQ was compared with 4 7-d dietary records (DRs) among 129 women. For the reproducibility study, the FFQ was administered twice, 1 y apart in 212 women. By conducting factor analysis, 3 major dietary patterns were identified: healthy (high in vegetables, fruits, fish, poultry, tomato, cereal, and low-fat dairy products), Western (processed meat, meat, refined grains, sweets, and fried potatoes), and drinker (beer, wine and liquor, snacks) pattern. These 3 patterns explained 29-34% of the total variance in these 2 studies. The Spearman correlation coefficients between FFQ1 and FFQ2 (reproducibility) for healthy, Western, and drinker pattern were 0.63, 0.68, and 0.73, respectively (all P < 0.0001). Correlation coefficients between the FFQ and DRs (validity) for these patterns were 0.59, 0.50, and 0.85, respectively (all P < 0.0001). Our results indicate that identification of dietary patterns through factor analysis is a reproducible and valid method. The dietary patterns approach might be used in nutritional epidemiology as an alternative method of dietary assessment.

Adult↗

Reproducibility, bioinformatic analysis and power of the SAGE method to evaluate changes in transcriptome.

The serial analysis of gene expression (SAGE) method is used to study global gene expression in cells or tissues in various experimental conditions. However, its reproducibility has not yet been definitively assessed. In this study, we have evaluated the reproducibility of the SAGE method and identified the factors that affect it. The determination coefficient (R2 ) for the reproducibility of SAGE is 0.96. However, there are some factors that can affect the reproducibility of SAGE, such as the replication of concatemers and ditags, the number of sequenced tags and double PCR amplification of ditags. Thus, corrections for these factors must be made to ensure the reproducibility and accuracy of SAGE results. A bioinformatic analysis of SAGE data is also presented in order to eliminate these artifacts. Finally, the current study shows that increasing the number of sequenced tags improves the power of the method to detect transcripts and their regulation by experimental conditions.

Animals↗

Temporal change in the reproducibility of a self-administered food frequency questionnaire.

The authors studied temporal change in the reproducibility of a self-administered food frequency questionnaire. During 1988-1994, 492 residents of a rural Japanese town completed five questionnaires including 27 food items, with intervals ranging from 2 weeks through 5.5 years. The reproducibility decreased steadily over time for pairs of the questionnaires administered in the same season (median Spearman's r at 2 weeks and 5 years = 0.62 and 0.28, respectively). The reduction was less marked for those surveyed in different seasons (median r at 5 months and 5.5 years = 0.35 and 0.28, respectively). The short-term, different season correlation at 5 months was lower than the short-term, same season correlation at 1 year. For individual food items, a lower initial reproducibility, infrequent consumption, and a larger difference in seasonal intake were associated with a greater reduction in reproducibility over time. The results indicate that reproducibility studies should deliberately choose the intervals and the seasons for surveys.

Epidemiologic Methods↗

Reproducibility and automatic measurement of QT dispersion.

This study investigated interobserver (two observers) and intrasubject (two measurements) reproducibility of QT dispersion from abnormal electrocardiograms in patients with previous myocardial infarction, and compared a user-interactive with an automatic measurement system. Standard 12-lead electrocardiograms, recorded at 25 mm.s-1, were randomly chosen from 70 patients following myocardial infarction. These were scanned into a personal computer, and specially designed software skeletonized and joined each image. The images were then available for user-interactive (mouse and computer screen), or automatic measurements using a specially designed algorithm. For all methods reproducibility of the RR interval was excellent (mean absolute errors 3-4 ms, relative errors 0.3-0.5%). Reproducibility of the mean QT interval was good; intrasubject error was 6 ms (relative error 1.4%), interobserver error was 7 ms (1.8%), and observers' vs automatic measurement errors were 10 and 11 ms (2.5, 2.8%). However QTc dispersion measurements had large errors for all methods; intrasubject error was 12 ms (17.3%), interobserver error was 15 ms (22.1%), and observers' vs automatic measurement were errors 30 and 28 ms (35.4, 31.9%). QT dispersion measurements rely on the most difficult to measure QT intervals, resulting in a problem of reproducibility. Any automatic system must not only recognize common T wave morphologies, but also these more difficult T waves, if it is to be useful for measuring QT dispersion. The poor reproducibility of QT dispersion limits its role as a useful clinical tool, particularly as a predictor of events.

Diagnosis, Computer-Assisted↗

Interobserver interpretative reproducibility of GOLDFISH, a first generation gold-facilitated autometallographic bright field in situ hybridization assay for HER-2/neu amplification in invasive mammary carcinoma.

Clinical laboratory testing for HER-2/neu gene amplification by fluorescence in situ hybridization is not widely used in diagnostic pathology laboratories. A bright field alternative permitting direct visualization of gene amplification using conventional microscopy may be more readily incorporated into routine diagnostic pathology practice. Interobserver reproducibility represents an important component of the validation of such an assay. We tested the hypothesis that a first-generation bright field alternative to fluorescence in situ hybridization, a Nanogold (Nanoprobes, Inc, Yaphank, NY, USA) (or gold-label)/autometallographic assay for HER-2/neu gene amplification in breast carcinoma, can be reproducibly interpreted by pathologists. Reference standard was direct fluorescence in situ hybridization supplemented by RNA/RNA in situ hybridization. Reproducibility of selected conventional histologic parameters was captured based on a hematoxylin and eosin slide accompanying the GOLDFISH preparation (gold-facilitated autometallographic in situ hybridization) as an indication of comparative reproducibility. The average kappa among GOLDFISH observers was 0.84, which was at least or concordant of observers scoring nuclear grade (kappa = 0.50) and the presence of in situ carcinoma (kappa = 0.57) by conventional histopathology. The GOLDFISH assay was specifically designed for qualitative interpretation, thus obviating the need for oil immersion microscopy and signal enumeration, and its interpretation was highly reproducible among five pathologists.

Breast Neoplasms↗