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Intersonographer reproducibility and intermethod variability of ultrasound measurements of carotid artery stenosis: The Tromsø Study.

BACKGROUND AND PURPOSE: Knowledge of the reproducibility of a diagnostic method is important in order to evaluate its usefulness. Few studies have examined interobserver and intermethod agreement on ultrasound measurements of carotid stenosis. METHODS: Intersonographer agreement on ultrasound measurements of carotid plaque morphology and the estimated degree of stenosis by three ultrasound methods were assessed in a random sample of 51 participants with stenotic carotid arteries selected from a population health survey. The degree of stenosis was assessed by measurements of velocity, lumen diameter reduction and cross-sectional lumen area. Intermethod agreement on the degree of carotid stenosis was also assessed. RESULTS: Agreement on plaque echogenicity and heterogeneity was moderate (kappa = 0.56 and kappa = 0.60, respectively). The mean degree of stenosis and median absolute difference between observers of the estimated degree of stenosis by the velocity method were 46.3 and 10.8%, respectively. The corresponding values were 51.0 and 5.8% for the diameter method, and 57.1 and 7.2%, for the cross-sectional lumen method. The limits of agreement for intersonographer reproducibility varied between +/-19.7 and 26.5%. For all methods, reproducibility increased with increasing degree of stenosis. Differences between the methods were large in low-grade stenosis but were acceptable in high-grade stenosis. CONCLUSIONS: Considerable differences in ultrasound measurement of stenosis, which could lead to different clinical conclusions, were regularly encountered no matter what ultrasound method was used.

Adult↗

Reproducibility of cystometry in overactive detrusor.

OBJECTIVE: To examine the reproducibility of cystometry in the overactive detrusor. METHODS: The study sample involved 30 patients of the placebo arm in double-blind clinical trials for an overactive detrusor. They had demonstrated detrusor overactivity and underwent the second cystometry after 2-4 weeks. Nonparametric tests for paired data were used to examine the reproducibility of four variables: volume at first desire to void, volume at first involuntary contraction, cystometric capacity, and the maximum pressure of involuntary contraction. Percent change and within-subject standard deviation were calculated to assess intraindividual variability. RESULTS: The second test results showed a significant and systematic change for the better. Volume variables increased by 10-13% (p<0.01), involuntary contraction was not elicited in 3 cases (10%), and the maximum contraction pressure decreased by 18% in the remaining cases. Intraindividual variability was not small. Seventeen patients (57%) demonstrated > or = 25% change in one or more variables, and the 95% confidence interval of cystometric capacity, for example, was calculated as (x -57, x +57), where x is a test result. No specific patients' demographics were found related to variability. CONCLUSION: Repeat cystometry in the overactive detrusor is not highly reproducible and may be subject to a systematic effect for the 'better'. Whether this is due to the placebo effect or the learning effect could not be determined.

Double-Blind Method↗

Reproducibility of a standardized titration procedure for the initiation of continuous positive airway pressure therapy in patients with obstructive sleep apnoea.

BACKGROUND: Manual titration of continuous positive airway pressure (CPAP) under polysomnographic control is the method most commonly employed to establish the minimal effective pressure (P(eff)) for the treatment of the obstructive sleep apnoea syndrome (OSA). To date, however, the reproducibility of P(eff) titrated in this way has not been investigated in any detail. OBJECTIVES: The present study aims to establish the reproducibility of P(eff) determined by manual titrations of CPAP under polysomnographic control in the sleep lab. METHODS: In a group of 50 patients (5 women), with a mean (SD) apnoea-hypopnoea index of 39.3 (21.8), apnoea index of 28.1 (20.9) and oxygen desaturation index of 39.3 (22.6), with newly diagnosed OSA, manual titration of CPAP was performed on two consecutive nights using the following standard titration protocol: starting at 4 mbar, CPAP was increased by steps of 1 mbar at intervals of at least 5 min, until no signs of airway obstruction could be seen, and arousals were no longer elicited. When no airway obstruction was detected over a period of 30 min, the pressure was lowered once during the night in steps of 1 mbar at intervals of at least 10 min, until obstructive events reappeared, whereupon the pressure was again increased as described above, until, once more, no signs of airway obstruction and no arousals occurred. The second titration was carried out in a blind manner, that is the lab technician did not know the results of the first pressure titration. RESULTS: The mean (SD) P(eff) for all titrations was 8.1 mbar (2.9). A high level of correlation was found between the P(eff) titrated on the first night and that titrated on the second night (Spearman correlation coefficient = 0.89). In a few individual cases, however, differences of up to 3 mbar were found between P(eff) on the first night and P(eff) on the second night. On average, the P(eff) measured on the second night was 0.5 mbar (SD = 1.3, range: -2.0 to 3.0 mbar) higher than that of the first night. CONCLUSIONS: With standardization of the manual titration of CPAP, P(eff) is readily reproducible. In individual cases, however, a difference of as much as 3.0 mbar between the two titrations is possible.

Adult↗

Thromboplastin Bilbao: reproducibility and sensitivity of a Spanish thromboplastin.

Prothrombin time (PT) is the control test for oral anticoagulant therapy as well as the screening test for defects of the extrinsic pathway of coagulation. Its responsiveness to decreased extrinsic clotting factors depends on the source and type of tissue factor thromboplastin extract. In 1994, a rabbit brain thromboplastin - Thromboplastin Bilbao (TBi) - was introduced as a replacement for a human brain preparation used since 1983, with the aim of establishing a national standard. The purpose of this study was to check the reproducibility, the inter-assay/intra-assay accuracy and the stability of this reagent under temperature changes and over time. A method modified from Frei et al. [World Health Organisation Regional Publications, Eastern Mediterranean Series, Alexandria, 1995] was used for the preparation of thromboplastin extract. Thirty-five batches of human TBi were prepared from 1983 to 1988, while from 1993 to 1999 13 batches of rabbit TBi were produced. The inter-assay reproducibility of rabbit TBi exhibited a coefficient of variation (CV) of 1.07-1.57% for normal plasma and of 1.25-2.56% for anticoagulated plasma. The intra-assay CV was 0.06-1.30% for normal plasma and 1.23-2.66% for anticoagulated plasma. The stability of the reagent to temperature changes and time was also estimated, with similar results for the two thromboplastins. As a result of the Oral Anticoagulant Treatment Quality Assessment Scheme in the Basque Country, an in-house rabbit thromboplastin with good sensitivity and reproducibility was developed.

Animals↗

Methods and reproducibility of measurement of resistivity in the calf using regional bioimpedance analysis.

UNLABELLED: The usefulness of regional bioimpedance analysis (RBIA) in determining the dry weight in dialysis patients is currently being investigated. The aim of this study was to evaluate the reproducibility of measurement of resistivity in the calf. METHODS: Twenty-five normal subjects and 10 patients undergoing regular hemodialysis were studied. Four electrodes inserted into a blood pressure cuff were placed on the calf. Bioimpedance was continuously measured over 3- to 5-min periods (Xitron Hydra). After a resting period of 1 min, cuff pressure was increased to above the systolic blood pressure (SBP) for a few seconds to expel excess ECF fluid and then deflated. The effect on recordings of moving the electrodes 2 cm higher and then 2 cm lower than the normal position was studied in 8 normal subjects. In a second study of reproducibility, post-dialysis measurements were made twice in 10 patients who maintained the same post-dialysis target weight throughout the study period. RESULTS: The mean resting resistivity rho(0) in normal subjects was 532.6 +/- 95 omega.cm rising to 583.9 +/- 99.7 omega.cm when cuff pressure was applied rho(p). The average values of rho(0) and rho(p) in patients post-dialysis were 489 +/- 74 and 537 +/- 77 respectively showing that there were no significant differences in rho(0) and rho(p) between normal subjects and patients post-dialysis. The mean values of change in resistivity when the electrodes were shifted between the lowest and highest positions on the calf were -3.66 +/- 4.45 and -1.44 +/- 3.82%, respectively. Repeat measurement of resistivity in patients post-dialysis varied by 2.04 +/- 2.29% while post-dialysis body weight varied by 0.17 +/- 0.47%. CONCLUSION: In this study, resistivity measurement by RBIA at the calf showed similar levels of fluid loading in patients post-dialysis as in normal subjects. This study also showed that change in electrode position resulted in a mean change in resistivity of <5% and repeated measurements showed a change in resistivity <3% while body weight changes were <0.2%. This technique appears to have an acceptable level of reproducibility for its application to the assessment of patient hydration.

Adult↗

Validity and reproducibility of a precoded questionnaire to assess fruit and vegetable intake in European 11- to 12-year-old schoolchildren.

BACKGROUND/AIMS: Validity and reproducibility were evaluated of a new questionnaire to assess fruit and vegetable intakes in 11- to 12-year-old children. METHODS: The precoded teacher-assisted self-administered questionnaire included two sections: a 24-hour recall part and a food frequency part. Validity was tested in 4 countries (Denmark, Iceland, Norway, Portugal; n = 43-60 per country) using a 1-day weighed food record and 7-day food records as reference methods. Test-retest (7-12 days apart) reproducibility was assessed in 6 countries (Belgium, Denmark, Iceland, Norway, Portugal, Spain; n = 60-74 per country). RESULTS: Spearman rank correlations for fruit and vegetable intake according to the frequency part and the 7-day food record ranged between r = 0.40-0.53. Between 25-50% were classified into the same quartile and 70-88% into the same or adjacent quartile. Test-retest Spearman rank correlations for the food frequency part were r = 0.47-0.84. Three countries showed no significant difference between fruit intake as assessed with the 24-hour recall part and the 1-day weighed food record, and 2 countries showed no significant difference for vegetables. In the other countries, the 24-hour recall part resulted in substantially higher mean intake levels. CONCLUSION: Validity and reproducibility as to ranking of subjects were regarded to be satisfactory in all countries. Group mean intake, based on the original 24-hour part, was valid for fruit in 3 countries and for vegetables in 2 countries, and this part was subsequently adjusted to avoid overestimation, before the questionnaire was used in the Pro Children study.

Child↗

Inter- and intraobserver reproducibility of cerebral atrophy assessment on MRI scans with hemispheric infarcts.

Cerebral atrophy (CA) in stroke patients is associated with poststroke dementia and may reflect underlying neurodegenerative pathology. Therefore, regional CA may be valuable to study in patients who develop poststroke dementia. The aim of this study was to test the reproducibility of a qualitative rating scale of CA on MRI. MRI scans were performed in 50 consecutive patients (age range 19-81) admitted for an acute hemispheric ischemic stroke. CA was assessed on 2 occasions 24 h apart, on axial T2-weighted sequences by 4 independent observers. We evaluated CA in 13 regions on a 0-3 scale. The sum of the subscores was called the CA score (range: 0-39). The level of agreement was expressed by kappa statistics as well as by analysis of variance for interexaminer reproducibility studies. The mean CA scores ranged from 2.8 to 11.0, indicating the low prevalence of CA in this sample. Complete agreement was reached in 41.7% during the first assessment and in 44.1% in the second assessment. The interobserver agreement was moderate in the first session (mean overall kappa: 0.48) and substantial in the second (mean overall kappa: 0.67). The intraobserver agreement was good for all raters (mean kappa: 0.65). Standardized to the range of the scale, standard deviations of the differences between CA scores of the 4 raters in the 2 sessions were 11.1 and 11.2%; within raters it was 4.4%. We conclude that the assessment of CA using this rating scale is possible in stroke patients. It provides regional atrophy measurements and is reproducible when performed by 1 rater.

Adult↗

The effect of placing a clear pit and fissure sealant on the validity and reproducibility of occlusal caries diagnosis.

The purpose of this in vitro study was to assess the validity and reproducibility of the diagnosis of fissure caries prior to and following the placement of a clear sealant. One hundred and twelve extracted molar teeth were examined by 7 experienced clinicians. Each examiner conducted four visual examinations, 2 prior to and 2 after sealing, allowing an assessment of reproducibility. The teeth were subsequently serially sectioned to provide the histological validation. After placement of a sealant, a significant (p < 0.05) loss of sensitivity was found for the diagnosis of enamel lesions and dentine lesions, but specificity was not altered. The overall reproducibility expressed by the kappa statistic was 0.60 and 0.47, before and after sealing, respectively. The examiners significantly (p < 0.001) underestimated the severity of lesions detected after sealing compared to their assessment prior to sealing. The investigation suggests that sealed surfaces require careful assessment and monitoring.

Dental Caries↗

Reproducibility and accuracy of three methods for assessment of demineralization depth of the occlusal surface: an in vitro examination.

This laboratory study of 100 occlusal surfaces investigated the reproducibility and accuracy of a visual ranked caries scoring system, an electronic caries scoring system (ECM) using a continuous conductance scale, and a radiographic ranked caries scoring system. Histological examination of the teeth served as a gold standard to validate the ability of each system to assess lesion depth and predict softened, demineralized dentine. After training, 3 examiners carried out each scoring system on two separate occasions. Kappa values for visual, ECM and radiographic ranked scoring systems showed good inter- and intra-examiner reproducibility levels and acceptable limits of agreement for ECM readings. When scoring systems were tabulated against histological scores there was a high correlation between the visual and ECM methods and lesion depth in both enamel and dentine, but radiographic examination could not detect enamel caries. When compared to the histological scoring, the Spearman correlation coefficients for the visual scoring ranged between 0.87 and 0.93, for the ECM between 0.80 and 0.85 and for the radiographic scoring system between 0.76 and 0.78. No tooth scored as visually sound had histological evidence of dentine caries. Soft dentine corresponded to demineralization involving the middle third of the dentine or more which was related to visual cavity formation or an ECM reading above 9 (score 3 or 4). The radiograph was an excellent predictor of soft dentine. In conclusion, the new visual system appears promising, but takes time to learn. The reproducibility and accuracy for the ECM is acceptable while radiographs miss early occlusal lesions.

Bicuspid↗

Reproducibility of vitreous fluorophotometry in patients with type 1 diabetes mellitus.

We assessed the day-to-day reproducible of vitreous fluorophotometry in 7 type 1 diabetic patients and in 1 healthy control subject. The coefficient of variation for duplicate measurements was 33.7, 40.3 and 23.6%, for the right eyes, the left eyes and mean values of both eyes, respectively. Assessment of reproducibility in 1 healthy subject, measured 4 times, resulted in coefficients of variation of about 60%. These values are somewhat worse than those obtained by others in healthy subjects. Since technical problems do not seem to play a significant role in this regard, our reproducibility results reflect the true biological variability of the permeability of the blood-retina barrier assessed by vitreous fluorophotometry in diabetic patients. This variability is substantial. Therefore, we conclude that this method is not precise enough to be used in intervention studies with a limited number of subjects.

Adult↗

Reproducibility of chronic infarct size measurement by contrast-enhanced magnetic resonance imaging.

BACKGROUND: The reproducibility of contrast-enhanced MRI has not been established. We compared MRI reproducibility for infarct size determination with that of (99m)Tc-sestamibi (MIBI) single photon emission computed tomography (SPECT). METHODS AND RESULTS: Patients with chronic myocardial infarction defined by enzymes (peak creatine kinase-MB 173+/-119 U/L) were scanned twice by MRI (MRI I and MRI II, n=20) and twice by SPECT (SPECT I and SPECT II, n=15) on the same day. The MRI contrast agent was injected during MRI I but not MRI II to test the effect of imaging time after contrast. Resting Tc-MIBI SPECT images were acquired and infarct size was determined with commercial software. Infarct size in patients scanned by MRI and SPECT was 14+/-6% of left ventricular mass (%LV) by MRI (range 4%LV to 27%LV) and 14+/-7%LV by SPECT (range 4%LV to 26%LV). MRI I and II scans were performed 10+/-2 and 27+/-3 minutes after contrast, respectively. For MRI, the difference in infarct size between scans I and II (bias) was -0.1%LV, and the coefficient of repeatability was +/-2.4%LV. For SPECT, bias was -1.3%LV, and the coefficient of repeatability was +/-4.0%LV. Within individual patients, no systematic differences in infarct size were detected when the 2 MRI scans were compared, the 2 SPECT scans were compared, or MRI was compared to SPECT. CONCLUSION: The size of healed infarcts measured by contrast-enhanced MRI does not change between 10 and 30 minutes after contrast. The clinical reproducibility of contrast-enhanced MRI for infarct size determination compares favorably with that of routine clinical SPECT.

Chronic Disease↗

Reproducible induction of early afterdepolarizations and torsade de pointes arrhythmias by d-sotalol and pacing in dogs with chronic atrioventricular block.

It has been well established that antiarrhythmic drugs can also have proarrhythmic effects such as torsade de pointes (TdP) arrhythmias. It was the purpose of this study to create an animal model with a high incidence of reproducible TdP that occurs under clinically relevant circumstances. Experiments were performed in anesthetized dogs that had been in chronic atrioventricular block for 9 +/- 6 weeks. TdP inducibility was attempted using different pacing modes before and after the administration of 2 mg/kg d-sotalol. In some experiments, endocardial monophasic action potentials were recorded. d-Sotalol increased the cycle length of the idioventricular rhythm (1475 +/- 460 to 1730 +/- 570 ms, P < .01) and the QT time (390 +/- 65 to 480 +/- 85 ms, P < .01). In 10% of the experiments, spontaneous TdP occurred after d-sotalol. The incidence of pacing-dependent TdP was 52% (P < .01). In the inducible group, the cycle length of idioventricular rhythm and QT time were significantly longer despite equal percentage increases in these parameters after d-sotalol in both groups. The pacing modes consisting of more than one frequency change had a higher TdP induction rate (P < .05). Reproducibility of TdP induction (three times or more using the same pacing train) remained present for approximately 60 minutes after d-sotalol and was greater than 90% within the same animal over weeks. TdP induction was related to the presence of early afterdepolarizations on the monophasic action potential recordings: five of six in the inducible group versus two of six in the nonresponders. Inducibility could be further increased to 89% when a second bolus of d-sotalol was administered to noninducible dogs. On the other hand, decreasing QT time by faster basic pacing or administration of isoproterenol, or MgSO4 prevented TdP induction. This effect of MgSO4 coincided with the disappearance of early afterdepolarizations. Our animal model shows a high incidence of reproducible acquired TdP arrhythmias, allowing study of the mechanism and treatment of TdP. TdP induction was related to the combination of a slow ventricular rate, the prolongation of QT time, a sudden induced rate change that often required two or more cycle length changes, and the presence of early afterdepolarizations.

Action Potentials↗

Reproducibility and clinical value of the trough-to-peak ratio of the antihypertensive effect: evidence from the sample study.

The objectives of our study were to assess the reproducibility of the trough-to-peak ratio (T/P) and to see whether a high T/P is accompanied by more organ protection or vice versa. The study included 175 (mean+/-SD age, 51+/-9 years) subjects with mild-moderate essential hypertension who had echocardiographic evidence of left ventricular (LV) hypertrophy taken from the SAMPLE study (Study on Ambulatory Monitoring of Blood Pressure and Lisinopril Evaluation), an open-label multicenter study. The study included a 3-week washout pretreatment period, a 12-month treatment period with lisinopril (n=84) or lisinopril plus hydrochlorothiazide (n=91) once daily, and a 4-week placebo follow-up period. Results of 24-hour ambulatory blood pressure monitoring and echocardiographic determination of left ventricular mass index (LVMI) were obtained before and after 3 and 12 months of treatment. T/Ps were computed in each patient by dividing the systolic and diastolic blood pressure changes at trough (changes in the last 2 hours of the monitoring period) by those at peak (average of the 2 adjacent hours with the maximal blood pressure reduction between the 2nd and 8th hour from drug intake) after 3 and 12 months of treatment. Average 24-hour blood pressure was similarly reduced at 3 and 12 months. Trough blood pressure changes at 3 and 12 months were closely correlated, as were the corresponding peak blood pressure changes. However, the 3- and 12-month T/Ps correlated to a lesser degree (r<0.42). Furthermore, the reduction of LVMI induced by treatment was similarly correlated with the treatment-induced reduction in 24-hour average, trough, and peak blood pressures but not with the T/Ps. This was also evident when the contribution to LV hypertrophy regression by 24-hour blood pressure changes and T/Ps was assessed in a multivariate regression analysis. In patients with a T/P >/=0.5 or <0.5, the regression of LVMI was similar. In conclusion, peak and trough blood pressure changes are reproducible and predict the regression of LVMI induced by treatment as well as average 24-hour blood pressure. T/Ps are less reproducible, and their value does not predict regression of organ damage by antihypertensive treatment.

Adult↗

Reproducibility of ultrasonographically determined intima-media thickness is dependent on arterial wall thickness. The Tromsø Study.

BACKGROUND AND PURPOSE: We compared the reproducibility of B-mode ultrasonographic measurements of intima-media thickness (IMT) in various segments of the right carotid artery and examined whether measurement error was associated with IMT or cardiovascular risk factor levels. METHODS: In 1994/1995 a total of 6676 participants in the Tromsø Study underwent ultrasound examination of common carotid artery IMT. Reproducibility of measurements was assessed by inviting 111 participants to a second ultrasound scan within 3 weeks of the first scan. On each occasion the subjects were examined by three sonographers. RESULTS: The mean between-observer absolute differences in IMT in the far wall of the bifurcation and the near and far walls of the common carotid-artery were 0.15, 0.10, and 0.08 mm, respectively. The corresponding within-observer differences were 0.15, 0.10, and 0.06 mm, respectively. Approximately 70% to 80% of total measurement variability was due to differences among sonographers; the rest was attributable to within-reader variability. Measurement error increased significantly with increasing IMT: the increase was more than twofold over the range of measurements. Cardiovascular risk factor levels were not associated with measurement variability when we controlled for IMT. CONCLUSIONS: We conclude that B-mode ultrasound provides reproducible estimates of the IMT in both the near and far walls of the carotid artery. Although measurement error is generally small, it increases proportionally with the level of IMT.

Aged↗

Reproducibility of measurements of cerebral infarct volume on CT scans.

BACKGROUND AND PURPOSE: Infarct volume is increasingly used as an outcome measure in clinical trials of therapies for acute ischemic stroke. We tested which of 5 different methods to measure infarct size or volume on CT scans has the highest reproducibility. METHODS: Infarct volume and total intracranial volume were measured with Leica Q500 MCP image analysis software, or with a caliper, on 38 CT scans of patients who participated in the Tirilazad Efficacy Stroke Study II (TESS II). The scans were performed 8 days (+/-2 days) after the onset of symptoms. The 5 methods tested were based on (1) semiautomated pixel thresholding, (2) manual tracing of the perimeter, (3) a stereological counting grid, (4) measurement of the 3 largest diameters, and (5) the single largest diameter. The measurements were performed independently by 2 observers; the first observer performed all measurements twice. RESULTS: The single largest diameter did not correlate well with infarct volume. Of the other methods, manual tracing of the perimeter of the infarct had the lowest intraobserver and interobserver variability: coefficients of variation were 8.6% and 14.1%, respectively. For total intracranial volume, manual tracing also provided the highest reproducibility: intraobserver and interobserver coefficients of variation were 3.3% and 4.9%, respectively. CONCLUSIONS: Manual tracing of the perimeter is the most reproducible method for measuring the volumes of the infarct and the total intracranial space in multicenter trials of therapies for acute ischemic stroke.

Adult↗

Invasive assessment of the coronary microcirculation: superior reproducibility and less hemodynamic dependence of index of microcirculatory resistance compared with coronary flow reserve.

BACKGROUND: A simple, reproducible invasive method for assessing the coronary microcirculation is lacking. A novel index of microcirculatory resistance (IMR) has been shown in animals to correlate with true microvascular resistance and, unlike coronary flow reserve (CFR), to be independent of the epicardial artery. We sought to compare the reproducibility and hemodynamic dependence of IMR with CFR in humans. METHODS AND RESULTS: Using a pressure-temperature sensor-tipped coronary wire, thermodilution-derived CFR and IMR were measured, along with fractional flow reserve (FFR), in 15 coronary arteries (15 patients) under the following hemodynamic conditions: (1) twice at baseline; (2) during right ventricular pacing at 110 bpm; (3) during intravenous infusion of nitroprusside; and (4) during intravenous dobutamine infusion. Mean CFR did not change during baseline measurements or during nitroprusside infusion but decreased during pacing (from 3.1+/-1.1 at baseline to 2.3+/-1.2 during pacing, P<0.05) and during dobutamine infusion (from 3.0+/-1.0 to 1.7+/-0.6 with dobutamine, P<0.0001). By comparison, mean values for IMR and FFR remained similar throughout all hemodynamic conditions. The mean coefficient of variation between 2 baseline measurements was significantly lower for IMR (6.9+/-6.5%) and FFR (1.6+/-1.6%) than for CFR (18.6+/-9.6%; P<0.01). Mean correlation between baseline measurements and each hemodynamic intervention was superior for IMR (r=0.90+/-0.05) and FFR (r=0.86+/-0.12) compared with CFR (r=0.70+/-0.05; P<0.05). CONCLUSIONS: Compared with CFR, IMR provides a more reproducible assessment of the microcirculation, which is independent of hemodynamic perturbations. Simultaneous measurement of FFR and IMR may provide a comprehensive and specific assessment of coronary physiology at both epicardial and microvascular levels, respectively.

Adult↗

The Ornstein-Uhlenbeck process does not reproduce spiking statistics of neurons in prefrontal cortex.

Cortical neurons of behaving animals generate irregular spike sequences. Recently, there has been a heated discussion about the origin of this irregularity. Softky and Koch (1993) pointed out the inability of standard single-neuron models to reproduce the irregularity of the observed spike sequences when the model parameters are chosen within a certain range that they consider to be plausible. Shadlen and Newsome (1994), on the other hand, demonstrated that a standard leaky integrate-and-fire model can reproduce the irregularity if the inhibition is balanced with the excitation. Motivated by this discussion, we attempted to determine whether the Ornstein-Uhlenbeck process, which is naturally derived from the leaky integration assumption, can in fact reproduce higher-order statistics of biological data. For this purpose, we consider actual neuronal spike sequences recorded from the monkey prefrontal cortex to calculate the higher-order statistics of the interspike intervals. Consistency of the data with the model is examined on the basis of the coefficient of variation and the skewness coefficient, which are, respectively, a measure of the spiking irregularity and a measure of the asymmetry of the interval distribution. It is found that the biological data are not consistent with the model if the model time constant assumes a value within a certain range believed to cover all reasonable values. This fact suggests that the leaky integrate-and-fire model with the assumption of uncorrelated inputs is not adequate to account for the spiking in at least some cortical neurons.

Action Potentials↗

Ozone-induced airway inflammatory changes differ between individuals and are reproducible.

To study whether the individual inflammatory response to ozone was reproducible, dose-dependent, and time-dependent, we performed two exposures to 250 ppb ozone, one to 125 ppb and one to filtered air, each for 3 h of intermittent exercise and separated by at least 1 wk. Twenty-one healthy and 15 asthmatic subjects participated in the study. One hour after the two exposures to 250 ppb ozone we observed a mean increase in sputum neutrophils of 17.9 and 17.9% in healthy and of 20.3 and 15.2% in asthmatic subjects (p < 0.05 each). Twenty-four hours after exposure, the respective values were 11.9 and 14.8%, and 9.1 and 16.1% (p < 0.05 each). In the whole group of subjects, individual changes in the percentage of neutrophils were significantly correlated between the two exposure days 1 h (r = 0.87, p < 0.001; intraclass correlation coefficient [Ri] = 0.86) as well as 24 h (r = 0.79, p < 0.001; Ri = 0.71) after exposure. The percentages of lymphocytes were increased 24 h after exposures (all subjects combined: p < 0.05). The decrease in FEV1 in both groups (p < 0.01), was also reproducible (r = 0.77, p < 0.001), but there were no correlations between changes in sputum parameters and lung function. Exposure to 125 ppb ozone caused a small increase (p < 0. 05) in the percentage of neutrophils in asthmatic subjects and in the concentrations of interleukin-8 in both groups combined. Our data demonstrate that inflammatory and lung function responses to ozone differ between individuals and are reproducible but not related to each other. Therefore, these responses appear to represent two independent factors underlying the airway response to ozone.

Adult↗