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Reproducibility of retinal thickness measurements in normal eyes using optical coherence tomography.

BACKGROUND AND OBJECTIVE: To determine the reproducibility of retinal thickness measurements in normal eyes using optical coherence tomography (OCT). PATIENTS AND METHODS: Multiple 3.20-mm vertical cross-sectional images through the center of fixation of consecutive patients with normal results on ocular examinations were obtained. Each image was divided into seven 320-micron segments. Regional retinal thicknesses for each section were measured using both the manually assisted (requiring observer localization of reflectivity peaks) and the automated modes (observer-independent measurement) of the computer software. RESULTS: Eighteen right eyes were studied. The mean coefficient of variation was less than 10% for all locations using the manually assisted method (average standard deviation less than 17 microns [range 9 to 16 microns]). The automated method was less reliable, with a coefficient of variation greater than 10% for locations within 500 microns of fixation. Automated measurements at fixation were the least reproducible because of poor internal limiting membrane reflectivity. CONCLUSION: OCT is capable of reproducible measurement of retinal thickness in normal eyes. Computer-driven, automated measurement of retinal thickness within 500 microns of fixation needs to be refined and its reproducibility reassessed in this region.

Adult↗

[Validation of the "Digest Questionnaire" for consistency and reproducibility with reference to upper abdominal symptoms].

"Digest" is a international effort to record the prevalence of digestive symptoms in the general population. The international questionnaire was tested in German translation for reliability and reproducibility. The questionnaire consists of 14 symptoms, which were investigated by standardized questions. Each symptom was described in 3 dimensions: frequency, severity and impact on daily activities. 127 successive patients referred for upper gastrointestinal endoscopy were interviewed twice by a young assistant and by an experienced gastroenterologist before the diagnostic work-up. A further 72 volunteers served as a control group. In these volunteers no upper gastrointestinal endoscopy was performed. Reliability and reproducibility were calculated by the Spearman rank test. The most frequent diagnoses were: organic diseases (oesophagitis [28], gastric ulcer/erosive gastritis [32] and duodenal ulcer [18]); functional diseases (dyspepsia [32] and irritable bowel syndrome [14]). Reproducibility was satisfactory by accepted standards (p > 0.7). Reliability was very good, with r-values for each symptom between p 0.96-0.99. The impact on daily activities was highest in the case of heart-burn or localized upper gastrointestinal pain, and lowest in the case of belching and fullness. The questionnaire can be easily administered by the non-specialist and the results discriminate well between functional/organic diseases and healthy people, thanks to excellent reproducibility and reliability.

Activities of Daily Living↗

Reproducibility of reported measurements of sun exposure in a case-control study.

We examined the reproducibility of the measurement of sun exposure in a cohort study of nonmelanocytic skin cancer in Geraldton, Western Australia. Two analyses were undertaken: a comparison of cutaneous sun damage with sun exposure reported at interview, and an analysis of test-retest reproducibility of reported exposure. Skin cancers and cutaneous indicators of sun damage (cutaneous microtopography and solar elastosis of the neck) were recorded at a survey in 1987. A case-control study was conducted in 1988 in which subjects were interviewed about their lifetime sun exposure. All subjects had European ancestry. A subset of these subjects was reinterviewed using the same interview schedule in 1993. The comparison of reported exposure with skin damage was restricted to 201 cases of basal cell carcinoma and 700 controls, all of whom were born in Australia and had no southern European ancestors. The analysis of test-retest reproducibility included 62 cases with basal cell carcinoma and 162 controls. After adjustment for the skin's sensitivity to sunlight, cutaneous microtopography explained 7% and solar elastosis of the back of the neck explained 13% of the variance in the reported time spent outdoors. The intraclass correlation between time spent outdoors reported in the two interviews was 0.77 [95% confidence interval (CI), 0.71-0.83], whereas for exposure to a specific anatomical site, it was 0.65 (95% CI, 0.55-0.73). The reported site-specific exposure was lower on the second occasion in controls but higher in cases. The hours of exposure on vacations and the proportion of exposure that occurred on nonworking days had poor reproducibility. Furthermore, cases reported a more intermittent pattern of weekly exposure on the first occasion than on the second, whereas the controls showed little difference in their pattern on the two occasions. The weighted kappa statistic for lifetime painful sunburns was 0.53 (95% CI, 0.41-0.66), and for lifetime number of blistering sunburns, it was 0.54 (95% CI, 0.44-0.65). Thus, the reported sun exposure showed only moderate agreement with biological markers of sun damage. Total sun exposure and, to a lesser extent, site-specific exposure showed good agreement on the two occasions. However, indicators of intermittent sun exposure had poor agreement, and sunburn had only fair agreement.

Adult↗

Classification of non-Hodgkin's lymphomas. Reproducibility of major classification systems. NCI non-Hodgkin's Classification Project Writing Committee.

An international, multi-institutional, clinical, pathologic study of 1175 cases of non-Hodgkin's lymphoma sponsored by the National Cancer Institute has offered a unique opportunity to investigate issues of reproducibility and agreement in pathologic classification. Teams of experienced hematopathologists reviewed all 1175 cases, with the "experts" utilizing their own classification system and the experienced panelists utilizing all six of the histopathologic classification systems. The fact that 20% of the slides were randomly repeated for a second interpretation allowed assessment of the reproducibility of any one given pathologist. In addition, the agreement between and among pathologists was evaluated. Results of this retrospective study showed that both experts and panelists were able to identify follicular (nodular) or other indolent lymphomas with 95% probability of concurrence between initial and later interpretations. Moreover, individual pathologists agreed with others in identifying and classifying these follicular features with approximately 90% probability of agreement. The reproducibility for individual pathologists, based on the 20% of cases that were randomly repeated, varied from a probability 0.53 to 0.93. Comparisons of intersystem predictability demonstrated that no one system predicted for any of the other systems within any major degree of reliability. This inability to "translate" from one system to another is thought to be a reflection of the problems of both interpathologist agreement and intrapathologist reproducibility. Flaws in study design are discussed and the usage of the working formulation of non-Hodgkin's lymphomas, in addition to classification by traditional schemas, is strongly encouraged.

Bone Marrow↗

Interlaboratory reproducibility of mobility parameters in capillary electrophoresis for substance identification in systematic toxicological analysis.

An interlaboratory pilot study was performed to determine the reproducibility of mobility parameters in capillary zone electrophoresis (CZE) and micellar electrokinetic chromatography (MEKC). The study was performed by an intended small number of laboratories (three) that used different brands of instruments (two). The effective mobility was corrected using standards by a method that was recently introduced to obtain a more reproducible migration parameter. A test set of 20 acidic test compounds and 5 reference compounds were analyzed during five days in each laboratory using CZE and MEKC. Buffers used consisted of 90 mM borate set at pH 8.4 (CZE) and 20 mM phosphate, 50 mM sodium dodecyl sulfate set at pH 7.5 (MEKC). Analyses were carried out using fused-silica capillaries at an electric field strength of either 52.6 kV/m or 37.5 kV/m. The interlaboratory reproducibility (mean RSD) of the effective mobility was 3.0% for CZE and 6.7% for MEKC. After applying the correction method, these values became 3.0% for CZE and 3.3% for MEKC, which is adequate for systematic toxicological analysis (STA) applications. A significant improvement of reproducibility for the calculated corrected effective mobility mu(eff)c was observed when variations are high. Therefore, it is recommended to use the correction method in interlaboratory situations, especially when instruments and capillaries from different manufacturers are used.

Calibration↗

Reproducibility of the French-American-British classification of acute leukemia: the Southwest Oncology Group Experience.

After initial French-American-British (FAB) diagnosis by a multiinstitutional Southwest Oncology Group panel, slides of acute leukemia cases were recirculated to panel members for second review. The reproducibility of the FAB classification is analyzed. The classification is reproducible in the 70% range in panel reviewer hands and allows remarkable reproducibility in the morphologic and cytochemical distinction of acute lymphoid leukemia (ALL) from acute myeloid leukemia (AML). The limitations of a morphologic and cytochemical classification of acute leukemia are discussed. A simplification of the FAB system, merging M1, M2, and M4 as M7, is proposed; this simplification improves the system's reproducibility.

Acute Disease↗

Reproducibility of coronary arteriographic reading in the coronary artery surgery study (CASS).

Eight hundred seventy arteriograms from the Coronary Artery Surgery Study (CASS) were independently read by readers at two different clinics to evaluate the reproducibility of the interpretation of coronary arteriograms. Among proximal segments, the interpretation of lesions of the left main coronary artery were the least reproducible, P less than .02. When one angiographer reads a stenosis of 50% or more in the left main coronary artery, it is estimated that a second reader will report no lesion 18.6% of the time. In 94.7% of the films, the number of significantly (greater than or equal to 70% stenosis) diseased vessels was the same for both readers (72.1%) or differed by one vessel (22.6%). The reproducibility of interpretation of films of good or acceptable quality or completeness was better than the reproducibility of readings of arteriograms judged to be of poor quality or incomplete studies. The mean absolute difference between readings of the percent stenosis decreased over the time of the patient enrollment, 1975 to 1978. This may have resulted from major collaborative efforts made during the course of the study to improve the quality of angiography and to standardize the reading of the cine films.

Angiography↗

Sensory thresholds in older adults: reproducibility and reference values.

To evaluate the test-retest reproducibility of vibratory perception (VPT) and thermal discrimination (TDT) thresholds on the foot in older adults, we examined 20 50-76-year-old subjects with, and 19 without non-insulin-dependent diabetes mellitus. Adjusted reference values for both thresholds were obtained by assessing the relations with age, body height, and sex among 216 subjects with normal glucose tolerance, of the same age, sampled randomly from a geographically defined general population. The VPT appeared to be more reproducible than the TDT (reliability coefficient 0.89 vs. 0.54). The reproducibility of the VPT was inversely related to age and better for men than for women. Diabetes and glycemic level did not affect the reproducibility of either threshold. Both thresholds were related to age and height. Women had a higher VPT than men. The relations between sex and sensory thresholds at the lower limb, reported in previous studies, were probably confounded by height.

Age Factors↗

Self-reproducing system can behave as Maxwell's demon: theoretical illustration under prebiotic conditions.

The recent discovery of polymerase activity in a ribosomal RNA intervening sequence as well as other studies of RNA-replicating systems suggest that the first living molecules were RNAs called replicases. According to this suggestion from biochemical studies, the replicase system is chosen as the simplest case of self-reproducing systems, and the fundamental problem of "what is life" is theoretically investigated by analysing the behavior of a replicase system with a supply of organic materials under prebiotic conditions. In this analysis, it is essential to consider (i) self-reproduction on the basis of its own information, (ii) maintenance and improvement of the information by selection and (iii) environmental event of non-biologically generating organic materials from inorganic matter by photochemical reactions, probably occurring in prebiotic conditions on the Earth. The replicases can retain and further elevate their self-reproducibility through competition among their descendant mutants for acquiring a limited quantity of materials, if the initial ability of self-reproduction and the concentration of replicases are above some critical values. By this selection, the replicase molecules retain a narrowed range of nucleotide sequences, or a state of lower entropy, against the natural tendency of sequence divergence, but this entropy reduction is sufficiently compensated by the entropy production in the environmental event of energy conversion from photons to heat. Once the stability of a self-reproducing system is established in the above sense, the self-reproducing system can operate as Maxwell's demon to regulate the outside flow of matter by its catalytic function without any contradiction to the second law of thermodynamics.

Animals↗

A new dynamometer measuring concentric and eccentric muscle strength in accelerated, decelerated, or isokinetic movements. Validity and reproducibility.

A new computerized dynamometer (the SPARK System) is described. The system can measure concentric and eccentric muscle strength (torque) during linear or nonlinear acceleration or deceleration, isokinetic movements up to 400 degrees.s-1, and isometric torque. Studies were performed to assess: I. validity and reproducibility of torque measurements; II. control of lever arm position; III. control of different velocity patterns; IV. control of velocity during subject testing; and, V. intra-individual reproducibility. No significant difference was found between torque values computed by the system and known torque values (p greater than 0.05). No difference was present between programmed and external measurement of the lever arm position. Accelerating, decelerating and isokinetic velocity patterns were highly reproducible, with differences in elapsed time among 10 trials being never greater than 0.001 s. Velocity during concentric and eccentric isokinetic quadriceps contractions at 30 degrees.s-1, 120 degrees.s-1 and 270 degrees.s-1 never varied by more than 3 degrees.s-1 among subjects (N = 21). Over three days of testing, the overall error for concentric and eccentric quadriceps contraction peak torque values for 5 angular velocities between 30 degrees.s-1 and 270 degrees.s-1 ranged from 5.8% to 9.0% and 5.8% to 9.6% respectively (N = 25). The results indicate that the SPARK System provides valid and reproducible torque measurements and strict control of velocity. In addition, the intra-individual error is in accordance with those reported for other similar devices.

Adult↗

Reproducibility of colonoscopic findings in Crohn's disease: a prospective multicenter study of interobserver variation. Groupe d'Etudes Therapeutiques des Affections Inflammatoires du Tube Digestif (GETAID).

We have examined prospectively whether it was possible for a multicenter group (12 centers) to standardize data collection and to achieve a reasonable level of reproducibility of colonscopic findings in Crohn's disease. Each colonoscopy was performed simultaneously by a pair of endoscopists who did not communicate with each other until they had completed a standardized form. A preliminary period was necessary to achieve an agreement on items to be recorded and on lesion definition. Thereafter 112 colonoscopies were carried out by 18 intracenter endoscopist pairs (both endoscopists from the same center) and 21 colonoscopies by 14 intercenter endoscopist pairs (endoscopists from different centers) in patients with Crohn's disease. The following data were recorded: (1) for each segment involved--rectum, sigmoid, and left colon, transverse colon, right colon, and ileum--the nature of elementary lesions (by ticking on a list of nine items) and an estimation of the surface of lesions and of ulcerations on two linear analog scales; and (2) a global assessment of lesion severity on a five-point scale and on a linear analog scale. Reproducibility of lesion detection was fair to excellent (kappa values greater than 0.54, P less than 0.05 or less) except, in the intercenter study, for erythema and swollen mucosa. Agreement on estimation of diseased and ulcerated segmental surfaces was good (intraclass correlation, coefficient, r, greater than 0.85; P less than 0.001) in both intra- and intercenter studies. Global assessment of lesion severity on a five-point scale (intra- and intercenter kappa = 0.64 and 0.55, respectively; P less than 0.001) and on a linear analog scale [intra- and intercenter r = 0.86 (P less than 0.001) and 0.58 (P less than 0.01), respectively was reproducible. In conclusion, reproducible endoscopic data can be collected by a cooperative multicentric group and thus be used in controlled therapeutic trial in Crohn's disease.

Academic Medical Centers↗

Short-term biological reproducibility of serum fatty acid composition in children.

To assess the biological day-to-day reproducibility of the fatty acid composition in serum lipid fractions in children on their habitual diets, fasting serum specimens were collected from healthy 8- to 9-year-old boys at 2-day (n = 21) or 7-day (n = 19) intervals. Percentage compositions of fatty acids in serum cholesteryl esters (CE), triglycerides (TG), free fatty acids (FFA) and phospholipids (PL) were analyzed by gas chromatography. The reproducibility was estimated by calculating linear correlation coefficients between the values obtained at the two time-points. Generally the correlations were higher in CE and PL than in TG and FFA. In CE the 7-day correlations of major fatty acids were only slightly lower than the 2-day ones. In PL the impairment of correlations was somewhat greater than in CE, but in TG and FFA there was a marked drop in reproducibility from 2- to 7-day intervals. The 2-day correlation coefficients of the percentages of linoleate, dihomo-gamma-linolenate, arachidonate and eicosapentaenoate in CE were 0.95, 0.84, 0.91 and 0.92, respectively. In PL, the respective values were 0.86, 0.82, 0.95 and 0.90. The present results indicate high short-term biological reproducibility of fatty acid composition in serum CE and PL and clearly lower in those of TG and FFA.

Child↗

Reproducible gene expression measurement among multiple laboratories obtained in a blinded study using standardized RT (StaRT)-PCR.

BACKGROUND: A method that provides standardized data and is relatively inexpensive and capable of high throughput is a prerequisite to the development of a meaningful gene expression database suitable for conducting multi-institutional clinical studies based on expression measurement. Standardized RT (StaRT)-PCR has all these characteristics. In addition, the method must be reproducible. StaRT-PCR has high intralaboratory reproducibility. The purpose of this study is to determine whether StaRT-PCR provides similar interlaboratory reproducibility. METHODS AND RESULTS: In a blinded interlaboratory study, expression of ten genes was measured by StaRT-PCR in a complementary DNA sample provided to each of four laboratories. The average coefficient of variation for interlaboratory comparison of the nine quantifiable genes was 0.48. In all laboratories, expression of one of the genes was too low to be measured. CONCLUSION: Because StaRT-PCR data are standardized and numerical and the method is reproducible among multiple laboratories, it will allow development of a meaningful gene expression database.

Binding, Competitive↗

Identification of reproducible ventricular tachycardia in a canine model.

Epicardial mapping was used as a standard to investigate how well the limb leads, both alone and in conjunction with 5 select epicardial electrodes, can verify reproducibility in a common, open-chest canine model of ventricular tachycardia (VT). Reproducible VT was defined as 2 or more episodes of monomorphic VT with similar rates, limb lead tracings and epicardial maps. In this study, 21 dogs underwent 2-hour occlusion of the left anterior descending coronary artery followed by reperfusion. Three days later, programmed stimulation was used to induce VT that was analyzed with limb leads I, II and III and 27 simultaneously recorded, bipolar epicardial electrodes. Thirteen dogs had VT of which 11 had polymorphic VT (varying QRS morphology). Twelve dogs yielded at least 1 form of monomorphic VT. Eight had 2 or more distinct forms of monomorphic VT (pleomorphism). Four of these 8 dogs had pleomorphic VT that was not apparent from the limb lead tracings, but was recognized from the epicardial activation maps constructed from the 27 epicardial recordings. To provide a method of distinguishing various VTs without the need of full epicardial mapping, 5 of the 27 epicardial electrodes were selected. These were positioned over the midanterior and midposterior right and left ventricles, and the left ventricular apex. By analyzing electrogram morphology and activation time, VT reproducibility could be as accurately identified with these 5 electrodes as with epicardial mapping derived from 27 electrodes. In conclusion, multiple VT morphologies are common in this open-chest canine model. Limb lead recordings alone are inadequate for analysis of VT reproducibility.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Daily reproducibility of electrophysiologic test results in malignant ventricular arrhythmia.

The reproducibility of electrophysiologic testing on successive days was assessed in the absence of antiarrhythmic drug treatment. Forty-two patients, 17 with compromising ventricular tachycardia and 25 with ventricular fibrillation unrelated to myocardial infarction, underwent 2 baseline studies. During the first electrophysiologic study, arrhythmia was induced in 32 of 42 patients (76%); however, during the second study a similar endpoint was reached in only 22 patients (52%) (chi 2 = 5.12, p less than 0.05). Only 18 of the 32 patients (56%) with induced arrhythmia during the first study had a reproducible result. Reproducibility was not related to presence of coronary artery disease, nature of presenting arrhythmia, or endpoint achieved (sustained or nonsustained ventricular tachycardia) during electrophysiologic study. Hence, reproducibility of endpoint during electrophysiologic investigation should be ascertained in each patient before initiating serial drug studies.

Adolescent↗

Reproducibility of topographic measurements with the optic nerve head analyzer.

We evaluated the reproducibility of optic nerve head contour mapping by the Optic Nerve Head Analyzer with ten recordings and analyses of one eye each in ten normal volunteers and ten analyses of a single recording in three of the eyes. Reproducibility was good for cup-to-disk ratio and neural rim area. Reproducibility was poor for cup volume, which was inversely related to cup size. Instrument and operator error were low for cup-to-disk ratio and neural rim area, but high for cup volume. Subjective comparisons of contour lines from five recordings of six eyes implied good reproducibility of this measurement.

Glaucoma↗

Reproducible vasodilatation by platelet-activating factor in blood- and Krebs-perfused rat kidneys is albumin-dependent.

The vasodilator effect of platelet-activating factor (PAF) and its reproducibility was determined in rat kidneys perfused in situ with blood or in isolated kidneys perfused with Krebs solution or Krebs plus 0.25% bovine serum albumin (BSA) at 3 ml/min. Dilatation was measured as inhibition of the increase in perfusion pressure produced by stimulation of the renal nerves or by infusion of noradrenaline. PAF, in saline and 0.25% BSA, was infused into the perfusate at 0.05 ml/min to produce eight incremental consecutive concentrations from 3 x 10(-11) to 10(-7). Two sets of PAF infusions were made during nerve-stimulated responses followed by one set during noradrenaline infusion. With blood perfusion, PAF consistently produced dose-dependent dilatation and 3 x 10(-9) M reduced nerve-stimulated responses to 52% of control. This effect was reproduced by a second infusion. However in Krebs-perfused kidneys the effect of the first PAF infusion was not consistent, with responses either not affected or reduced only at the lower doses so that the mean maximum decrease was only 10% and the vasodilatation was not dose-dependent. The second PAF infusion invariably had no effect. On the other hand perfusion with Krebs and 0.25% BSA produced consistent and dose-dependent inhibition of vasoconstriction which was reproduced by a second infusion. PAF was effective at 10-fold lower doses in Krebs-albumin perfused compared to blood-perfused kidneys. These results indicate that exogenous PAF is a potent and reproducible dilator of the rat renal vasculature perfused with blood or Krebs-albumin solution but not albumin-free Krebs solution.

Animals↗

Reproducibility of the densitometric analysis of fluorescein angiograms.

Computer-aided operator-interactive densitometry was applied to assess the reproducibility or retinal-fluorescein angiograms. To achieve this, the fundus camera images of glass tubings of various diameter filled with fluorescein of varying concentrations were subjected to densitometric analysis. These studies were carried out repeatedly at 9-micrometer and 29-micrometer scanning resolutions by three observers and thus the inter- and intra-operator errors could be estimated. The scanned data were analyzed as both optical densities and intensities for some of the measurements. In both analyzing modes good linearity was obtained when the densitometric response was plotted against tubing diameter for various concentrations. To determine the reproducibility of transit time and retinal circulation time analyses, a randomly selected patient's angiogram was repeatedly analyzed by three observers and compared. From these data the inter- and intra-operator errors were also determined for successive frames and the reproducibility of the area under the dye dilution curves for both arteries and veins was computed. The overall densitometric reproducibility was found to be good; however, practical usefulness of the retinal circulation time remains to be established.

Angiography↗