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Assessment of the reproducibility of the lactulose H2 breath test as a measure of mouth to caecum transit time.

The lactulose H2 breath test is in use as a simple non-invasive measurement of mouth to caecum transit time, but its reproducibility has never been assessed. We have examined the reproducibility of mouth to caecum transit time in 21 normal subjects using lactulose 10, 15, and 20 g; seven subjects being studied with 10 g and 12 each with 15 and 20 g doses. Transit time decreased with increasing doses of lactulose although the differences were not significant between or within (n = 5) individuals. Variation in transit times between individuals was considerable with all doses of lactulose (mean coefficient of variation of 18.5, 29.7 and 28.3% with 10, 15, and 20 g respectively). The addition of lactulose to a liquid meal containing carbohydrate, fat, and protein decreased the coefficient of variation to less than 10% in four subjects studied. The lactulose H2 breath test could be made more reproducible by including a liquid meal.

Adult↗

Reproducibility of echocardiographic estimates of left ventricular dimensions.

Although echocardiography is ideally suited for repetitive use on a patient for evaluation of left ventricular function, the value of this application is minimised by the uncertainty as to whether changes in left ventricular dimensions observed on a patient at different times or by different observers are real or result from the ultrasonic beam penetrating the left ventricle at different angles. Accordingly, an instrument was designed and constructed in our laboratory to improve the reproducibility of echocardiographic measurements of left ventricular dimensions. The instrument represents an orthogonal reference frame by means of which the spatial orientation of the ultrasonic beam relative to the chest is determined and reproduced in subsequent studies, while the point of entrance of the beam is marked on the chest wall. Using this instrument, left ventricular echograms were initially recorded on a group (I) of 23 subjects with or without heart disease and the study was repeated 8 hours to 49 (mean 7) days later by the same observer and also, in 16 cases, by an independent observer. The average values from 2 to 6 (mean 4) heart cycles were used for the left ventricular end-diastolic dimension (Dd), end-systolic (Ds) dimension, and their difference (delta D). Differences in all three variables between studies were random and statistically insignificant, never exceeding 3-5 mm for Dd or Ds, and 4 mm for deltaD. For comparison, left ventricular internal dimensions were also obtained in a seprate group (II) of 14 subjects by the standard method of using the mitral valve as an internal landmark, without the benefit of this instrument. All 14 subjects had the initial study repeated within 8 hours to 11 (mean 3-8) days later by the same and also by an independent observer. Though in the group as a whole there was no significant difference in left ventricular dimensions between studies, individual variations reached 11 mm for Dd, 9 mm for Ds, and 9 mm for deltaD, and the degree of scatter was significantly larger than in group I. This initial experience indicates that the use of this instrument improves the reproducibility and enhances the reliability of estimates of echocardiographic left ventricular dimensions and function on a patient examined at different times by the same or independent observers.

Adolescent↗

Interobserver reproducibility of histological features in cutaneous malignant melanoma.

AIMS: To assess the interobserver reproducibility of certain histological features proposed for the diagnosis of melanoma. METHODS: In a series of melanomas, 13 histological parameters were analysed: dimension > 6 mm, asymmetry, poor circumscription, irregular confluent nests, single melanocytes predominating, absence of maturation, suprabasal melanocytes, asymmetrical melanin, melanin in deep cells, cytological atypia, mitoses, dermal lymphocytic infiltrate, and necrosis. RESULTS: The agreement (reproducibility) between the nine observers was excellent (kappa > 0.75) for 10 of the 13 examined features (dimension > 6 mm, poor circumscription, irregular confluent nests, single melanocytes predominating, absence of maturation, suprabasal melanocytes, asymmetrical melanin, melanin in deep cells, mitoses, and necrosis). The agreement for asymmetry was very close to excellence (kappa = 0.74), and that for cytological atypia (kappa = 0.65) and dermal lymphocytic infiltrate (kappa = 0.47) was slightly lower, but in the fair to good agreement range. The kappa values obtained by comparison with the majority diagnosis were generally high (> or = 0.85); the mean value of kappa was lower (0.70) for only one parameter (dermal lymphocytic infiltrate). CONCLUSIONS: The parameters investigated showed an overall good reproducibility.

Humans↗

Analysis of reproducibility of subjective grading systems for breast carcinoma.

The inter- and intra-observer reproducibility of three grading systems for breast cancer has been analysed: those of the World Health Organisation, of Black, and of Hartveit. In addition, the components forming the basis of these grading systems were analysed separately with regard to reproducibility and interrelationship. In this analysis, degree of differentiation was also included as a parameter. The grading systems of WHO and of Black gave a stratification of the material into three categories of tumours, but that of Hartveit did not. All three systems had a low inter- and intra-observer reproducibility. Truncated component analysis indicated that the grading systems of WHO and of Black are closely related to each other and to the 'nuclear lobulation' component of Hartveit's system. The components 'pleomorphism', 'mitotic frequency', and 'hyperchromasia' of the WHO system were closely interrelated. Descriptors such as 'differentiation' and 'tubule formation' were interrelated but acted in a different direction from the others.

Breast Neoplasms↗

Reproducibility of the visual evoked potential using a light-emitting diode stimulator.

The intersubject and intrasubject reproducibility of the VEP was evaluated using two different methods of producing pattern reversal--a mirror/projector system and a light-emitting diode (LED) system. Intersubject reproducibility was determined in 100 normal subjects (50 males, 50 females). Ten subjects were studied on ten different occasions over 11 months to establish intrasubject reproducibility. The two methods gave comparable results. It is concluded that the mirror/projector system has no advantages over the LED system, which is cheaper, more robust and more convenient. Most of the intersubject variability was found to be due to subject variables and it is concluded that technical improvements are unlikely to reduce further the variability of the test. A variability in the latency of P100 of up to 7.7 ms was recorded in the serial studies on the ten subjects, indicating that in longitudinal studies on patients, changes in latency must exceed 9-10 ms to be significant. With both stimulus systems, there were significant sex-related differences in latency (P50 and P100 but not N70) and amplitude (N70-P100). The extent of the difference was such that the upper limit of normal latency for P100 (2.5-3 SD from the mean) was 4.2-4.7 ms longer for males than females-a value which exceeds 1 SD. Separate control values for males and females are advisable whichever method is used to produce pattern reversal.

Adolescent↗

Reproducibility and comparison of responses to inhaled histamine and methacholine.

The efficiency of a standardised inhalation test procedure was studied by examining the reproducibility of responses to histamine and methacholine. In addition, the responses to the two agents were compared. Each set of duplicate tests was carried out on a separate day within one week, and all factors known or presumed to influence responses were carefully controlled. The results were expressed as the provocative concentration of the agent causing a 20% fall in forced expired volume in one second (PC20). Responses to histamine and methacholine were highly reproducible (coefficients of determination [r2] = 0.994 and 0.990 respectively). Responsiveness to histamine correlated closely with responsiveness to methacholine (r2 = 0.85). There was a small but significant cumulative dose effect with methacholine (P less than 0.01) but not with histamine. Side effects of throat irritation, flushing, and headache were more frequent with histamine than methacholine, and were dose-related. The high level of reproducibility indicates the efficiency of the test procedure. The similar severity of effects by agents with different mechanisms of action suggests that the primary cause of non-specific bronchial hyperreactivity lies at the level of bronchial smooth muscle.

Adult↗

Histamine dose-response curves in asthma: reproducibility and sensitivity of different indices to assess response.

In 18 clinically stable asthmatic patients histamine inhalation challenges were performed with a Wright's nebuliser and tidal volume breathing for two minutes on two to four occasions for each subject at a maximum interval of two weeks. The response was measured in terms of specific lung conductance (sGL) by the subtraction technique, maximum partial and maximum complete expiratory flow at 40% and 50% of vital capacity respectively (Vmax40p and Vmax50c), and FEV1 from the maximum flow-volume curve. Dose-response curves were analysed for (1) provocative concentration (PC) of histamine causing a 20% fall in FEV1 and a 40% change in the other measurements; (2) threshold concentration (TC)--the concentration at which changes in the measurement exceed 2 SD from control values; (3) reactivity (R)--the slope of the dose-response curve beyond TC. We found that PC20-FEV1 was the most reproducible index, the 95% confidence intervals based on a single determination being +/- 1.6 single two-fold concentration difference. PC20-FEV1 was more reproducible than PC values for other measurements and more reproducible than any of the TC values. The 95% confidence intervals based on a single determination of R varied from +/- 52% to +/- 74% change/log histamine concentration. Both sGL and Vmax40p detected the bronchoconstrictor response assessed by PC and TC at a significantly lower histamine concentration than FEV1 (p less than 0.01 and p less than 0.05 respectively). PC and TC results showed a significant correlation, but neither were correlated with R.

Adult↗

Serum prolactin concentration in pseudopregnant and normally reproducing goats.

Previous experiments with bromocriptine suggested that prolactin plays a role in the aetiology of pseudopregnancy in goats. Serum prolactin concentration was measured in a herd of white Dutch dairy (Saanen) goats when hydrometra (a typical characteristic of pseudopregnancy) was diagnosed by ultrasound, during the spontaneous development of pseudopregnancy, and in normally reproducing goats during the breeding season. In the normally reproducing does the prolactin concentration decreased at the beginning of the breeding season. In 12 of 14 pseudopregnant goats the prolactin concentration was within the range observed in the normally reproducing goats on the day that hydrometra was diagnosed. In two goats the prolactin concentration was low during the first few weeks of pseudopregnancy and in a third it fluctuated. There was no correlation found between the concentration of prolactin and the development or the presence of a persistent corpus luteum. These results suggest that prolactin does not play a crucial role in the aetiology of pseudopregnancy in the goat.

Anestrus↗

Serial reproducibility of conductance catheter volumetry of left ventricle in conscious dogs.

Although the conductance catheter technique has been currently applied to in situ measurement of left ventricular volume, reproducibility of this method has not been examined within the same subject on separate days. Accordingly, serial catheter volumetries (mean 5 days apart) were performed in 10 normal conscious dogs, which were chronically instrumented with the conductance catheter, a micromanometer, and caval cuff occluders. Left ventricular end-systolic pressure-volume relationship was also determined during transient caval occlusion. All hemodynamic variables were compared at the same heart rate. There were no significant changes in blood resistivity (10 +/- 7 omega cm, 8%) and the parallel conductance of the surrounding tissues (7 +/- 6 ml, 10%). The mean difference was 3 +/- 2 ml (7%) for end-diastolic volume and 3 +/- 2 ml (11%) for end-systolic volume. Stroke volume and ejection fraction were also reproducible with mean difference of 2 +/- 1 ml (9%) and 3 +/- 2% (8%) respectively. The end-systolic pressure-volume relationships were nearly superimposable with the slope being 6.05 +/- 1.82 mmHg/ml on day 1 and 6.13 +/- 2.22 mmHg/ml on day 2. The difference averaged 0.63 +/- 0.42 mmHg/ml (11%). These results suggest that highly reproducible volume estimates by conductance catheter offer its feasibility of serial assessment of ventricular performance in vivo.

Analysis of Variance↗

Small-sample reproducibility estimates: an example using rebreathing measurements.

We developed a statistical technique to estimate the reproducibility of a parameter from a population in which only two repeated measurements can be made in a single individual. The following data were analyzed: acetylene cardiac output (Qc), lung tissue volume (Vti), and carbon monoxide diffusing capacity (DLCO) measured by rebreathing techniques in a population of 86 healthy subjects (51 men and 35 women). Each subject was measured twice with a computerized rebreathing system using a test gas of 10% He-0.3% C18O-0.7% C2H2-25% O2-balance N2 while sitting at rest. The estimated coefficients of variation for repeated measurements were 6.8, 10.3, and 5.7% for Qc, Vti, and DLCO, respectively. Chebyshev's inequality was used to estimate the imprecision for a single measurement of these parameters and for averages of two or more repeated values. A single measurement of Qc would be within 14.2% of a "true" mean 90% of the time, whereas an average of three consecutive measurements would be within 8.2% of the true mean 90% of the time. Single measurements of Vti and DLCO were found to be within 21.7 and 12.0%, respectively, of the true mean 90% of the time. When three consecutive measurements are averaged, Vti is within 12.6% and DLCO is within 6.9% of the true mean 90% of the time. We conclude that 1) rebreathing Qc is as reproducible as other measurements of cardiac output, 2) rebreathing measurements of DLCO are as reproducible as those made by the single-breath technique, and 3) an average of two to three measurements of Vti should be made to obtain values with a reasonable degree of precision.

Acetylene↗

Ultrasound: a reproducible method to measure conduit vein compliance.

Classical venous occlusion plethysmography (VOP) of the leg, often used to assess venous compliance, measures properties of the whole calf, including volume changes at the arterial side and the interstitial fluid accumulation that occurs as a result of the enhanced capillary pressure during venous occlusion. We present an ultrasound technique to measure the compliance of one major conduit vein in the leg. Ultrasound measurements of the popliteal vein were compared with classical VOP measurements, which were performed simultaneously in one subject. Six healthy individuals were measured on three occasions to assess short- and long-term reproducibility of the measurements. Six motor complete spinal cord-injured (SCI) individuals were included to compare venous compliance in subjects with known pathological changes of the venous system with controls. The ultrasound and VOP measurements of venous compliance correlated significantly (r(2) = 0.39, P = 0.001). Ultrasound provides reproducible measurements with short- and long-term coefficients of variation ranging from 10 to 15% for popliteal vein compliance and from 2 to 9% for absolute diameters at the different venous pressure steps. In addition, by using ultrasound, we were able to detect an 80% reduction in the compliance of the popliteal vein in SCI individuals compared with controls (P < 0.01). In conclusion, ultrasound is a suitable and reproducible method to measure conduit vein compliance and provides the possibility to specifically assess compliance of one vein instead of the whole calf.

Adult↗

Interobserver reproducibility of DNA-image-cytometry in ASCUS or higher cervical cytology.

In the present study, the aim has been to investigate the interobserver reproducibility of DNA-image-cytometry (DNA-ICM) applied to routine Pap smears classified as Atypical Squamous Cells of Undetermined Significance (ASCUS) or higher lesions (ASCUS+). 202 Pap smears diagnosed as ASCUS or higher were included in the study. After cytological assessment, smears underwent restaining according to Feulgen. First measurements were performed as routine workup. The second measurements were blinded to the result of the first and consecutively performed. DNA-ICM met the consensus statements of the European Society of Analytical Cellular Pathology (ESACP). Interobserver agreement was assessed by calculating Kappa statistics. The diagnosis of DNA-aneuploidy in the first measurements was confirmed in all cases. Second measurement detected 12 additional cases with aneuploidy. Nine out of these cases were classified as aneuploidy by detection of 9c Exceeding Events (9cEE). In three cases stemline-aneuploidy was disclosed. The overall proportion of observed agreement was 94.1%, kappa=0.87, 95% CI=0.74-0.99. Our study shows a good interobserver reproducibility of DNA-ICM performed on cervical smears with ASCUS or higher lesions. DNA-ICM thus represents a highly reproducible diagnostic procedure.

Adolescent↗

Induction of reproducible focal ischemic lesions in neonatal mice by photothrombosis.

Focal stroke during the perinatal and neonatal period is a significant cause of cognitive and behavioral deficits. Currently, the number of models available to study neonatal brain injury is limited and many are technically difficult to induce in neonatal rodents. We demonstrate a reproducible method to induce a focal ischemic injury in the cerebral cortex of neonatal mice that utilizes the principle of photothrombosis. Postnatal day 7 pups were anesthetized and systemically administered rose bengal (50 mg/kg). Permanent focal ischemia was induced in the medial frontal cortex and somatosensory cortex by irradiating surface blood vessels with a laser (532 nm). By placing a mask having an aperture of defined shape and size on the skull surface, we were able to reliably and reproducibly induce infarcts in discretely defined cortical regions. Further, we demonstrate explicit control of infarct volume by modifying the duration of laser exposure. This tool will provide a means for researchers to safely, easily and noninvasively induce reproducible ischemic lesions in specified regions of the neonatal cortex.

Animals↗

Effect of placing a clear sealant on the validity and reproducibility of occlusal caries detection by a laser fluorescence device: an in vitro study.

The principal aim of this in vitro study was to assess the validity and reproducibility of the detection of occlusal caries using laser fluorescence (LF), prior to and following the placement of a clear fissure sealant. It also aimed to compare the manufacturer's standard cut-off recommendations with those published for in vitro studies and to compare the validity and reproducibility of LF with clinical visual examination (CVE) for the detection of occlusal caries under sealants. Three clinicians independently examined visually and with LF 37 extracted teeth (25 molars, 12 premolars), with a range of clinical caries from apparently sound to cavitated dentinal caries. Examinations were conducted under dental surgery conditions. Subsequently, the teeth were serially sectioned to provide the validating criterion. Following placement of the sealant, the specificity generally increased but there was an associated loss of sensitivity, at both the D1 (enamel and dentine) and D3 (dentine) diagnostic thresholds. The LF readings were significantly lower after placement of the sealant (p<0.05). The manufacturer's recommended cut-offs appear to be the most appropriate to use. The CVE had superior validity and reproducibility when compared to LF. Overall, the placement of a clear sealant does influence the detection of caries by LF but does not prevent the detection of caries by this method.

Bicuspid↗

Reproducibility of repeated mountings of a noninvasive CT/MRI stereoadapter.

The reproducibility of a noninvasive computed tomography (CT)/magnetic resonance imaging stereoadapter was tested on 12 healthy volunteers. The adapter was easy to mount and detach without discomfort. Two repeated mountings of the adapter showed a good reproducibility in relation to the scalp. When extrapolated to a hypothetical target in the right thalamus, the mean differences between the two mountings were 0.07 mm in the lateral, 0.16 mm in the anteroposterior and 0.17 mm in the height coordinates. This high degree of reproducibility seems to permit a safe CT-guided functional stereotaxis, where the preoperative CT scanning can take place on one day and the surgery may be performed on any other suitable day.

Adult↗

Qualitative assessment of cerebral atrophy on MRI: inter- and intra-observer reproducibility in dementia and normal aging.

To assess the reproducibility of a qualitative rating scale of cerebral atrophy on MRI in an aged population of demented and non-demented individuals, 4 raters independently judged cerebral atrophy (CA) in 13 regions on a 0-3 scale on 75 MRI scans, on two occasions. 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 13.3 to 21.2, indicating moderately high prevalence of cerebral atrophy in this sample. Complete agreement among observers was reached in 49.7% of the ratings during the first assessment and in 44.1% in the second assessment. The inter-observer agreement was poor in both sessions (mean overall kappas 0.34 and 0.24). The intra-observer agreement was moderate to good for all raters (mean overall kappa: 0.58). The average standard deviation of the differences between CA scores of the 4 raters was 5.12 in the first and 5.13 in the second session. The average standard deviation for the differences within raters was 2.4. We conclude that the assessment of cerebral atrophy using this rating scale on MRI in an aged population has a poor reproducibility among raters. However, it provides regional atrophy measurements and is quite reliable when performed by a single rater.

Aged↗

Reproducibility of ischaemic lactate metabolism during atrial pacing in man.

The reproducibility of myocardial ischaemia provoked by atrial pacing was studied in two groups of patients. The heart rate was slowly increased (10 beats per fourth min) until angina in group A, and quickly increased (10 beats per 20 s) in group B. Cardiac venous flow was measured by thermodilution and blood was sampled for metabolic studies at rest and during the maximum obtained heart rate and repeated after 20 min of rest. Ischaemia was defined as a reduction in myocardial lactate extraction ratio by 50% and to a ratio lower than 0.15. Lactate metabolism changed from production (-0.06 +/- 0.05) during the first pacing to extraction (0.05 +/- 0.05) during the second in group A (p less than 0.02). Lactate metabolism was quite reproducible in group B. All the other metabolic and haemodynamic parameters were unchanged in both groups. We conclude that the duration of atrial pacing is important for the reproducibility of pacing-induced myocardial ischaemia.

Cardiac Pacing, Artificial↗

Reproducibility of thallium-201 myocardial imaging.

Seventy-six thallium-201 myocardial perfusion studies were performed on twenty-five patients to assess their reproducibility and the effect ofvarying the level of exercise on the results of imaging. Each patient had a thallium-201 study at rest. Fourteen patients had studies on two occasions at maximum exercise, and twelve patients had studies both at light and at maximum exercise. Of 70 segments in the 14 patients assessed on each of two maximum exercise tests, 64 (91%) were reproducible. Only 53% (16/30) of the ischemic defects present at maximum exercise were seen in the light exercise study in the 12 patients assessed at two levels of exercise. Correlation of perfusion defects with arteriographically proven significant coronary stenosis was good for the left anterior descending and right coronary arteries, but not as good for circumflex artery disease. Thallium-201 myocardial imaging at maximum exercise is reproducible within acceptable limits, but careful attention to exercise technique is essential for valid comparative studies.

Adult↗