Angiogenesis in breast cancer: a comparative study of the observer variability of methods for determining microvessel density

The purpose of this study was to evaluate the reliability of different methods for estimating neovascularization in breast cancer and to compare them in terms of observer variability. The microvessel endothelium was stained immunohistochemically by antibodies against CD34. The investigated methods included Chalkley counting, estimation of intratumoral microvessel density (MVD) by one hot-spot, MVD by the mean value of three hot-spots, and the highest value of MVD in three hot-spots. In addition, we applied stereology in the quantification of angiogenesis in the whole tumor section by random and systematically distributed sampling fields. Each of forty tumors was measured with all methods, twice by the same observer and once by another observer. Observer variation was analyzed by orthogonal regression, estimating the slope and intercepts with 95% confidence intervals (CI), and by analysis of agreement using difference plots. Intraobservationally, the methods had variations of the same magnitude (coefficient of variation [CV] approximately 20%). Interobservationally, the stereologic estimate of vessel profiles, Q(A), from the whole tumor section and the Chalkley counting method had the lowest variation (CV approximately 21%), with a small contribution by observers alone (CV 8% to 9%). Interobservationally, the MVD methods had considerable variation with a large contribution by observers alone (CV approximately 30%), which was lowest using the mean of three hot-spots. Correlation slope and 95% CI of Chalkley were 1.18 (0.95, 1.48), CV 20%; slope of MVD (mean) was 1.14 (0.91, 1.43), CV 31%; and slope of MVD (max) was 1.15 (0.92, 1.45), CV 36%. The slope of MVD on one hot-spot was 1.33 (1.08, 1.63); CV 38%. Additional measurements performed using a conference microscope, eliminating subjectivity in hot-spot selection and field sampling, optimized the reproducibility: slope was 1.02 (0.99, 1.04); CV of differences, 3.5%. On the other hand, reproducibility was not necessarily optimized by choosing the same hot-spot area, because variation in selecting a microscopic field could yield different counting numbers. The stereologic estimation of QA based on the whole tumor section had a high reproducibility, with low variation due to observers. The Chalkley and MVD methods had moderate reproducibility, and the Chalkley method had low variation due to observers alone. For all methods, the biologic variation among patients was the major contributor to the total variation. The Chalkley and MVD methods have been published to provide significant prognostic estimates in breast cancer, but the Chalkley method has less observer variation and may be superior from a methodologic point of view.     

Laparoscopic removal of gonads containing on occult seminoma in a woman with complete androgen resistance

Although nomograms to convert readings of resistance (R) and reactance (Xc) into estimates of body composition have begun to emerge for children as well as adults, there has been reluctance to use bioelectrical impedance analysis (BIA) in very young children due to the irritability of children, measurement instability, positioning of electrodes, and, of course, reproducibility of measurements. The precision of completely independent measurements of BIA indices was evaluated by two observers by comparing a series of 40 measurements of R and Xc and 36 measurements for weight in four malnourished children on 10 different days during the course of their nutritional recuperation. For weight, the CV (coefficient of variation) was 3.5% for observer A and 3.8% for observer B. There were no differences in the means across observers with respect to weight, R, and Xc. The results obtained in this study illustrate that properly trained observers following the same standards can produce equivalent data for BIA and weight measurements even in sick children.     

Reproducibility of fat area measurements in young, non-obese subjects by computerized analysis of magnetic resonance images

OBJECTIVE: To assess reproducibility, expressed as both inter-observer variability and intra-observer variability, of fat area measurements on images obtained by magnetic resonance (MR); to compare variability between fat area measurements, calculated from a single image per body region and from the average fat area of three images, and to determine reproducibility of image acquisition at the abdominal level. SUBJECTS: Thirty young, non-obese subjects (reproducibility of image analysis) and nine young, non-obese subjects (reproducibility of image acquisition). METHODS: Three MR images at the level of the abdomen (in 30 subjects) and at the level of the hip and thigh (in 14 of them). Quantification of subcutaneous fat depots (abdomen, hip and thigh) and visceral fat depots using an image-analyzing computer program. Assessment of variability of image analysis for fat area measurements between two observers and within observers. Assessment of reproducibility of image acquisition at the abdominal level (in nine subjects). RESULTS: Subcutaneous fat areas in all body regions were quantified with coefficients of variation (CV) ranging from only 2.1%-4.9%. By contrast, visceral fat area measurements showed markedly higher CVs (range: 9.4%-17.6%). Moreover, relative variability was much larger in small visceral fat areas (CVs up to 25.6%). The majority of CVs, calculated for intra-observer variability and calculated from the average fat area measurements of three images, was lower than calculated for inter-observer variability and for one single image, respectively. In particular, for the visceral fat depot, this reduction in variability had practical consequences for the number of subjects required for a study. Variation of repeated image acquisition was in the same range as variation of repeated measurements on the same image. CONCLUSION: One image per body site is sufficient to obtain a reliable estimate of subcutaneous fat depots. For estimations of the visceral fat depot, the average area measurements of three images reduces variability and increases statistical power. The availability of one single experienced observer during a study adds to accuracy.     

The reproducibility of the results of transvaginal sonography of the uterus in patients with abnormal uterine bleeding

Our objectives were to determine the reproducibility, or interobserver agreement, of transvaginal sonographic imaging of the uterus in patients with abnormal uterine bleeding and to identify the effect of observer experience. Transvaginal ultrasound findings of 235 patients with abnormal uterine bleeding were recorded systematically on videotape. Recordings were reviewed by three observers who had different levels of experience, and who were asked to judge the endometrium/uterine cavity and myometrium separately as being normal, abnormal or inconclusive, according to predefined criteria. Reproducibility was expressed by the observed rates of interobserver agreement and by kappa statistics. The differences in agreement between observer pairs were analyzed by means of McNemar's chi 2 test. The observed rates of agreement for the judgement of the endometrium/uterine cavity varied from 0.85 to 0.89, with a kappa value ranging from 0.70 to 0.78 between observers. The judgment of the myometrium resulted in agreement rates of 0.86-0.91 and kappa values of 0.67-0.80. Although the effect of experience was evident, the differences in agreement between observers were not significant (p > 0.01). The reproducibility of the results of transvaginal sonography of the uterus in patients with abnormal uterine bleeding was good. Observations of the endometrium/ uterine cavity with a normal appearance were the most highly reproducible, with the smallest effect of observer experience. This may reduce the need for invasive diagnostic procedures in patients with abnormal uterine bleeding.     

Effect of the contour line on cup surface using the Heidelberg Retina Tomograph

BACKGROUND: Significance of topometric follow-up examinations of the optic nerve head in glaucomatous eyes depends on the reproducibility of the calculated parameters. Since the definition of the standard reference plane in software version 1.11 of the Heidelberg Retina Tomograph has been changed, intrapapillary parameters depend directly on the position of the contourline in the sector between -10 degrees to -4 degrees, and therefore on the observer variability to determine the disc border. We evaluated intra- and interobserver variability and present a simple approach to increase reproducibility. METHOD: The disc border of 4 glaucomatous eyes, 3 ocular hypertensive eyes and 3 eyes of healthy subjects were traced by two observers, 5 times using the free draw mode and 5 times by the addition of contourline circles. RESULTS: We found a median variability of the mean disc radius in sector -10 degrees to -4 degrees of 51 microns, which defines the position of the standard reference plane, resulting in a median variability of the position of the standard reference plane of 33 microns which caused a variability of 81 microns2 of the cup area. Addition of contourline circles smoothing the final contourline along the border of the optic disc resulted in a decrease of the coefficient of variation of the standard reference plane of 3.76% (6.76% vs. 3.0%), of the cup area of 2.34% (3.87% vs. 1.53%) and of the rim volume of 3.41% (9.75% vs. 6.34%). CONCLUSION: The calculation of the cup area using software version 1.11 of the Heidelberg Retina Tomograph depends on observer variability. The addition of contourline circles to define the final contourline along the disc border increases reproducibility. However, in follow-up of topometric examinations of the optic nerve head the software supported transfer mode should be used. Comparing topometric data of an individual optic disc in follow-up suppose the same definition of the contourline. Therefore, topometric data evaluated using software version 1.10 or earlier needs to be recalculated.     

Intraobserver and interobserver variance in the measurement of ultrasound-estimated bladder weight

Recently, we reported that ultrasound-estimated bladder weight (UEBW) could be used as a noninvasive tool in evaluating the degree of bladder hypertrophy. This study was designed to test the reproducibility of its measurement. The overall mean UEBW of the initial measurement and that of the second one by one observer in 36 cases was 42.8 +/- 22.6 g and 42.9 +/- 22.6 g, respectively. The paired differences between two measurements ranged from -3.4 to 2.7 g, with a mean difference of only -0.1 g. The interobserver variance was also slight. The paired differences between UEBW measurements derived from the two observers in 32 cases ranged from -6.0 to 7.9 g, with a mean difference of only 0.1 g. The Cochran's test statistic of the measurements of UEBW was 0.142 for one observer and 0.130 for two, which were less than its 5% critical value. Due to these favorable characteristics, UEBW could be reliable tool for the investigation of bladder hypertrophy with a sufficient reproducibility.     

Solution structure of a DNA complex with the fluorescent bis-intercalator TOTO modified on the benzothiazole ring

The aim of the present study was to evaluate and compare the reproducibility of cephalometric landmarks on (1) conventional films, and images acquired by storage phosphor digital radiography both on (2) hardcopy and (3) monitor-displayed versions. The material consisted of 19 cephalograms for each image modality. The phosphor plates were scanned in an image reader and the 10-bit normalized, raw data digital images were converted to 8-bit TIFF images for PC monitor-display. The digital hardcopies were produced in a laser printer. Six observers were asked to record 21 cephalometric landmarks on each conventional film, hardcopy, and monitor-displayed image. For the films and hardcopies, the landmark co-ordinates were recorded via a digitizing tablet. For the monitor-displayed images, the co-ordinates were recorded directly from the monitor using a dedicated Windows-based cephalometric program. Reproducibility was defined as an observer's deviation (in mm) from the mean between all observers. Differences between the image modalities and between the observers were tested by two-way analysis of variance for each landmark. There was a statistically significant difference between the reproducibility of film, hardcopy and monitor-displayed images in 11 of the 21 landmarks. There was no unequivocal trend that one modality was always the best. For a full cephalometric recording (the sum of all 21 landmarks), the monitor-displayed images (mean = 25.3 mm) had a lower precision than film (P < 0.005) and hard-copy (P < 0.02). There was no significant difference between film (mean = 21.8 mm) and hardcopy (mean = 22.8 mm). The lower reproducibility seen for the monitor-displayed images is most probably of little clinical significance.     

Effects of a new positioner on the precision of hip bone mineral density measurements

In an attempt to reduce patient positioning errors, the authors tested the use of a new hip-specific positioning tool, OsteoDyne's Hip Positioner System (HPS). The HPS is an "A" frame splint designed to abduct both legs approximately 15 degrees to hold them in full extension at the hips and knees and to lock the feet in a neutral position. Seventy volunteer women aged 35-82 years were randomly assigned in two age-matched groups (mean age 56 years). Each group underwent two consecutive femur dual X-ray absorptiometry (DXA) scans with intermediate repositioning using the HPS system and two others utilizing the standard hip positioner provided with Hologic and Lunar scanners. One technician performed all scans using a Hologic QDR 1000-Plus and Lunar DPX-Plus densitometer. One hundred and fifty volunteer women aged 50-84 years (mean age, 64 years) were recruited in a multicenter study for the assessment of precision. Each subject underwent three consecutive femur DXA scans with intermediate repositioning using the HPS system. The coefficient of variation (CV) was significantly improved at the femoral neck by the use of the HPS with 0.7 versus 1.2 with the Hologic densitometer but only moderately altered at other sites. Similar results were found with the Lunar densitometer with improvement of precision at the femoral neck, 0.8 versus 1.8 with a similar trend but no significant difference at the other regions. No statistical difference was noted between the femoral neck BMD measured with the HPS system and with the standard positioners in either group. The mean precision of data obtained on the QDR 1000+ was 0.8% (range 0.1-1.4) for the femoral neck BMD, 1.1% (range 0.1-3.0) for the trochanter BMD, 2.3% (range 0.2-5.2) for Ward's triangle BMD, and 0.8% (range 0.1-1.9) for the total femur BMD. The mean precision of data obtained on the QDR 2000 was 0.7% (range 0.1-2), 1% (range 0.1-4.9), 2.6% (range 0.3-5.7), and 0.7% (range 0.1-1.8), respectively. In conclusion, data obtained with the new OsteoDyne's HPS seem capable of reducing patient positioning errors for the hip measurement. Its use is likely to improve confidence in hip bone mineral density measurements.     

Observer agreement on interpreting colposcopic images of CIN

The purpose of this work was to study intraobserver and interobserver variation in the interpretation of colposcopic images of cervical intraepithelial neoplasia (CIN). Twenty-three experienced colposcopists were asked to assess colposcopic images presented on slides and to select the biopsy site. Eleven cases were independently interpreted twice with an interval of 2-3 months by all observers. No information about the cytological classification was available. In each case the "majority assessment" was considered as the standard, being "no CIN" in 2 cases, CIN I in 4 cases, CIN II in 3 cases, and CIN III in 2 cases. Intraobserver concordance was 66.7%, the kappa value was 0.54. Interobserver agreement was found to be 52.4 and 51.0% in the first and second sessions, respectively, while the mean kappa values were 0.41 and 0.33, respectively. In selecting the site for biopsy, 77.4% of all observers agreed while the same site was selected in 85.3% of cases by the individual colposcopist in the two sessions. Overall, CIN I and II interpretations revealed lower levels of agreement than no CIN or CIN III interpretations. It is concluded that observer variability in interpreting colposcopic images and selecting the site for biopsy is in the same range as observer variation in other subjective diagnostic tests such as cytology and histopathology. This variation should be taken into account in the colposcopical management of patients with abnormal cytology.     

Spontaneous pneumothorax in cocaine sniffers

PURPOSE: To evaluate intraobserver and interobserver reproducibility of measurements in images obtained by the 50 MHz Humphrey Ultrasound Biomicroscope. METHODS: The first stored image of central cornea, central anterior chamber, and angle structures obtained at 50 examinations were measured twice by three observers. Nine different parameters were measured in angle images and two in images of central cornea and anterior chamber. Intraobserver reproducibility was assessed by calculating the coefficient of variation and interobserver reproducibility by a two-ways ANOVA. RESULTS: Intraobserver reproducibility was high for all measurements of central cornea thickness and anterior chamber depth with a coefficient of variation (%) < or = 3.8%. In angle images the intraobserver reproducibility of measurements was often lower (coefficient of variation (%) 1.3-52.6%). The lower reproducibility was most noticeable in measurements involving the less defined structures. Interobserver reproducibility was poor. CONCLUSIONS: Comparison of measurements are best done of well defined structures and by only one observer.     

The determination of ultrasound velocity in the os calcis, thumb and patella during childhood

Maximising the accumulation of bone tissue during growth and puberty is one of the most important aims in the prevention of osteoporosis. For prevention studies in children it is necessary to develop methods for skeletal status without radiation. Ultrasonic velocity (speed of sound = SOS) has been proposed as an alternative method. Using a new ultrasonic system (Osteoson K4, Minhorst, Germany), we investigated the reproducibility and age-dependency of SOS in several peripheral bones in 218 children and young adults. Intra-observer (day to day) reproducibility: calcaneus CV = 0.64%, patella CV = 1.18% and thumb CV = 0.43% (n = 25). Inter-observer reproducibility: calcaneus CV = 1.1%, patella CV = 2.48% and thumb CV = 0.62% (n = 16). SOS in thumb and patella increased with age and peaked at 20-25 years. SOS in the calcaneus showed no increase after puberty. Studies in bones from pigs show no dependency of SOS from the thickness of analysed cortical or trabecular bone slices. We conclude that the reproducibility of SOS measurements especially in the thumb is comparable with those of radiation methods. The SOS data in growing, healthy children and the independency from bone dimensions provides more evidence that SOS describes the elastic qualities of the bones.     

Effect of ibudilast on microcirculation thrombosis in rat inner ear

Arterial wall thickening may be quantitatively assessed by measuring the intima-media thickness (IMT) with high resolution ultrasound. Previous studies have shown a good inter/intraobserver variability of IMT measurements in the common carotid. In this study we evaluated the inter/intraobserver variability of IMT measurements in 10 randomly selected asymptomatic subjects (age 55.4 +/- 6). Two carotids and two femorals were studied in each subject. IMT for each patient was the average of five IMT measurements at the artery bifurcation. Three observers repeated the scanning and the measurements twice with no knowledge of the previous readings. The between observer coefficient of variation (CV) was 8.45%; the intraobserver CV (mean of carotids and femorals) varied from 4.4 to 5.1% for the three observers who measured IMT three times. The mean absolute difference between the first and the third measurement was 0.0738 mm. In conclusion IMT measurement variability is mostly due to differences between observers. The intraobserver variability is very small. IMT measurements at the carotid and femoral bifurcations have a low variability and are a good expression of atherosclerosis as they consider early lesions at the bifurcation level which may not be observed in the common carotid.     

Reproducibility and comparability of insulin sensitivity indices measured by stable-label intravenous glucose tolerance test

We have investigated the reproducibility of (1) insulin sensitivity (S*I) and glucose effectiveness (S*G) as measured by the stable-label (one compartment) minimal model, and (2) insulin sensitivity (S*Ib), plasma clearance rate (PCR), basal hepatic output (HGOb), and total hepatic glucose output (HGO0-240) as measured by the novel stable-label two compartment model of glucose disappearance during labelled intravenous glucose tolerance test (IVGTT) using 6,6-(2)H-glucose. Ten normal male subjects were studied on two occasions one week apart. Both models provided estimates of all indices with acceptable precision (CV of parameter estimates < or =50%). The within subject CVs of S*I and S*Ib were comparable (17% vs 19%) as were the within subject CVs of S*G and PCR (13% vs 16%). A highly significant linear relationship was observed between S*Ib and S*I (0.303 +/- 0.046 ml kg(-1) min(-1) per mU l(-1) vs 13.04 +/- 1.89 10(-4) min(-1) per mU l(-1), y = 0.0037 x + 0.0002, r = 0.90, p < 0.001; mean +/- SE), but not between PCR and S*G (1.98 +/- 0.15 ml kg(-1) min(-1) vs 0.0089 +/- 0.0005 min(-1), rs = 0.34, NS). The two compartment model provided a plausible time-profile of hepatic glucose output during IVGTT, reproducible estimates of HGOb (1.96 +/- 0.18 mg kg(-1) min(-1), 15%; mean +/- SE, within subject CV), and a highly reproducible HGO0-240 (7%; within subject CV). We conclude that the stable-label (one compartment) minimal model and the stable-label two compartment model provide reproducible estimates of parameters of glucose kinetics in normal subjects. Insulin sensitivity indices estimated by the two models are strongly linearly related.     

Development of chitosan/polyethylene vinyl acetate co-matrix: controlled release of aspirin-heparin for preventing cardiovascular thrombosis

In a multicenter evaluation the precision and stability of single slice peripheral Quantitative Computed Tomography (pQCT) systems were assessed. Compared to central Europe the peripheral QCT device is also widely used in the Italian health care system. Phantoms were measured frequently on each machine in four pQCT scanners over a two-year period using an identical automated software program. Intrasite and intersite phantom mineral densities, expressed in units of mg/cm3, were analyzed and examined. The short and long term precision were estimated from the consistency of these measurements using the root mean square error and expressed as coefficient of variation in percent (% CV). Short term precision was good (mean intrasite coefficient of variation (CV) 0.21 +/- 0.056 standard deviation (SD)). Intersite measurements of a single phantom revealed differences between machines of the same type of not more than 2.9 mg/cm3. At four sites frequent phantom measurements revealed a mean CV of 0.18% (range 0.12-0.28). No significant changes in the regression slopes (drift of the machine versus time) were observed. We conclude that the in vitro precision and stability of the single slice pQCT systems are sufficiently high and unlikely to negatively affect the in vivo precision.     

The reproducibility of color Doppler duplex sonography in the measurement of renal arterial blood velocity

In this study, the reproducibility of color Doppler duplex sonography for repeated measurements of renal blood flow was evaluated in 14 healthy subjects. We examined the reproducibility for different examiners and different time intervals between the examinations. Doppler frequency sonograms were analyzed with several parameters, and statistical evaluation was performed by calculating both the correlation coefficient (r) and coefficient of variation (CV). Peak systolic velocity (S), early diastolic velocity (D1) and mean velocity (MV) showed good reproducibility (r = 0.902-0.992, CV = 2.15-8.16%). On the other hand, end-diastolic velocity (D2), acceleration time (AT) and acceleration index (AI) showed poor reproducibility. We conclude that the reproducibility of this method is acceptable for repeated measurements of renal blood velocity, using suitable parameters S, D1 and MV.     

Evaluation of low density spine software for the assessment of bone mineral density in children

Pediatric dual-energy X-ray absorptiometry spine scans often cannot be analyzed with standard software due to a failure to identify the bone edges of low density vertebrae. Low density spine (LDS) software improves bone detection compared with standard software. The objective of this study was to compare bone mineral density (BMD) measurements obtained with the standard and LDS software in 27 healthy nonobese, 32 obese, and 41 chronically ill children, ages 2-18 years. Lumbar spine (L1-L4) BMD, measured by standard analysis, ranged from 0.531-1.244 gm/cm2. Reanalysis with the LDS software resulted in a systematic increase (mean +/- SD) in estimated bone area of 17.0+/-5.0%, an increase in bone mineral content of 6.1+/-6.3%, and a mean decrease in BMD of 8.7+/-1.7% (all p < 0.001). This resulted in a mean decrease in BMD Z score of 0.7+/-0.2. Linear regression models, predicting standard BMD from LDS BMD, were fit for the three subject groups (R2 = 0.993-0.995). Small differences in slopes were detected across groups (p = 0.07); LDS BMD predicted higher standard BMD in obese subjects. In conclusion, LDS analysis resulted in a clinically significant decrease in measured BMD. The association between analysis methods was exceptionally high (R2 > 0.99), indicating that LDS BMD accurately predicts standard BMD. Although LDS BMD in obese subjects predicts higher standard BMD results than in nonobese subjects, the small difference is of questionable clinical significance. LDS software is a useful tool for the assessment of BMD in children.     

Prenatal diagnosis by analysis of fetal cells in maternal blood

Twenty-five fresh-frozen cadaveric specimens were used to evaluate the role of the syndesmotic ligaments when the ankle is loaded with external rotation torque. An apparatus was constructed that allowed pure external-rotation torque to be applied through the ankle with the foot in neutral flexion. The apparatus provided solid fixation of the tibia while allowing free movement of the fibula in all planes. The syndesmotic ligaments were incrementally sectioned, and direct measurements of anatomical diastasis were made. Mortise and lateral radiographs were made at each increment under both loaded (5.0 newton-meters) and unloaded conditions. After all structures of the syndesmosis had been divided, the syndesmosis was reduced and was repaired with one or two screws. The strength of the repair was measured with incremental increases in torque of 1.0 newton-meter. The radiographs were measured by three independent observers in a blind fashion. In order to evaluate intraobserver error, each observer was randomly given forty radiographs to reinterpret. Diastasis and rotation were found to be related to the amount of injury of the ligament (p < 0.0001). After the entire syndesmosis had been divided, application of a 5.0-newton-meter torque resulted in a mean diastasis of 7.3 millimeters. The subsequent repair of the anterior tibiofibular ligament with suture failed at a mean of 2.0 newton-meters (range, 1.0 to 6.0 newton-meters) of torque. Repair with two screws was found to be stronger than repair with one, with the first construct failing at a mean of 11.0 newton-meters (range, 5.0 to 15.0 newton-meters) and the second, at a mean of 6.2 newton-meters (range, 2.0 to 10.0 newton-meters) (p = 0.0005). Failure of the screw fixation was not associated with the maximum previous diastasis (p = 0.13). Measurements of anatomical diastasis were compared with measurements made on the mortise and lateral radiographs. Measurements on the stress mortise radiographs had a weak correlation with diastasis (r = 0.41, p < 0.0001). However, measurements on the stress lateral radiographs had a higher correlation (r = 0.81, p < 0.0001). Additionally, interobserver correlation was significantly higher for the measurements on the lateral radiographs (r = 0.87, p < 0.0001) than for those on the mortise radiographs (r = 0.56, p < 0.0001). Intraobserver correlation for the three observers was poor with regard to the measurements on the mortise radiographs (r = 0.12, 0.42, and 0.25). The respective correlations for the measurements on the lateral radiographs were r = 0.81, 0.90, and 0.89.(ABSTRACT TRUNCATED AT 400 WORDS)     

Laryngeal tumor volume measurements determined with CT: a study on intra- and interobserver variability

PURPOSE: To investigate the intra- and interobserver variability of computed tomography-based volume measurements of laryngeal tumors. METHODS AND MATERIALS: The volume of 13 laryngeal tumors was repeatedly measured by five independent observers in four different sessions, using the summation-of-areas technique. Mean tumor volume and its standard deviation were calculated for each tumor. Statistical analysis was done with analysis of variance, Spearman rank correlation, and linear regression. RESULTS: Both the effect of the observers (p < 0.0001) and the effect of the session (p < 0.01) on tumor volume was statistically significant. Interobserver variability was the most important component of total variability (89.3%). A significant rank correlation was found between mean volume and standard deviation (p < 0.01); the relationship between mean tumor volume and standard deviation can be described using linear regression [standard deviation = 0.28 volume + 0.35 (R = 0.79)]. CONCLUSION: Total variability in the computed tomography-based measurement of laryngeal tumor volume can be reduced by having the measurements done by a single trained observer.     

MRI screening for acoustic neuroma without gadolinium: value of 3DFT-CISS sequence

To evaluate the efficacy of a gradient-echo sequence (3DFT-CISS) in the diagnosis of acoustic neuromas, two independent observers twice reviewed the images of the temporal bones of 83 patients. Contrast-enhanced T1-weighted spin echo images were used as the reference, showing 18 acoustic neuromas, including 5 purely intracanalicular and one intralabyrinthine tumours. High sensitivity (89-94%), specificity (94-97%) and accuracy (94-95%) were found. Intraobserver (kappa 0.93-1) and interobserver (kappa 0.83-0.84) reproducibility were very good. The smallest intracanalicular tumour was overlooked twice by both observers; the intralabyrinthine tumour once by one observer. All tumours were detected with a less stringent decision criterion, at the expense of lower specificity.     

Submicrosecond pacemaker precision is behaviorally modulated: the gymnotiform electromotor pathway

What are the limits and modulators of neural precision? We address this question in the most regular biological oscillator known, the electric organ command nucleus in the brainstem of wave-type gymnotiform fish. These fish produce an oscillating electric field, the electric organ discharge (EOD), used in electrolocation and communication. We show here that the EOD precision, measured by the coefficient of variation (CV = SD/mean period) is as low as 2 x 10(-4) in five species representing three families that range widely in species and individual mean EOD frequencies (70-1,250 Hz). Intracellular recording in the pacemaker nucleus (Pn), which commands the EOD cycle by cycle, revealed that individual Pn neurons of the same species also display an extremely low CV (CV = 6 x 10(-4), 0.8 micro sec SD). Although the EOD CV can remain at its minimum for hours, it varies with novel environmental conditions, during communication, and spontaneously. Spontaneous changes occur as abrupt steps (250 ms), oscillations (3-5 Hz), or slow ramps (10-30 s). Several findings suggest that these changes are under active control and depend on behavioral state: mean EOD frequency and CV can change independently; CV often decreases in response to behavioral stimuli; and lesions of one of the two inputs to the Pn had more influence on CV than lesions of the other input.