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An investigation of the reproducibility and usefulness of automatic couch motion in complex radiation therapy techniques.

Radiation therapy techniques that incorporate multiple couch motions are becoming more common, and they often involve an increasing level of complexity along with a need for automatic motion. The reproducibility of automatic couch motion is thus a growing concern. In this work we carried out various tests to assess the automatic motion of a commercial treatment couch, including tests to evaluate the digital readout reproducibility, as well as an independent verification of the reproducibility of the couch positions on repeated motions, using phantoms as well as a volunteer subject. It was shown that the couch motion is highly reproducible, with no discomfort to the patient, and can greatly improve treatment times as well as reduce errors in couch positioning.

Humans↗

Comparison of methods based on different molecular epidemiological markers for typing of Mycobacterium tuberculosis complex strains: interlaboratory study of discriminatory power and reproducibility.

In this study, the currently known typing methods for Mycobacterium tuberculosis isolates were evaluated with regard to reproducibility, discrimination, and specificity. Therefore, 90 M. tuberculosis complex strains, originating from 38 countries, were tested in five restriction fragment length polymorphism (RFLP) typing methods and in seven PCR-based assays. In all methods, one or more repetitive DNA elements were targeted. The strain typing and the DNA fingerprint analysis were performed in the laboratory most experienced in the respective method. To examine intralaboratory reproducibility, blinded duplicate samples were included. The specificities of the various methods were tested by inclusion of 10 non-M. tuberculosis complex strains. All five RFLP typing methods were highly reproducible. The reliability of the PCR-based methods was highest for the mixed-linker PCR, followed by variable numbers of tandem repeat (VNTR) typing and spoligotyping. In contrast, the double repetitive element PCR (DRE-PCR), IS6110 inverse PCR, IS6110 ampliprinting, and arbitrarily primed PCR (APPCR) typing were found to be poorly reproducible. The 90 strains were best discriminated by IS6110 RFLP typing, yielding 84 different banding patterns, followed by mixed-linker PCR (81 patterns), APPCR (71 patterns), RFLP using the polymorphic GC-rich sequence as a probe (70 patterns), DRE-PCR (63 patterns), spoligotyping (61 patterns), and VNTR typing (56 patterns). We conclude that for epidemiological investigations, strain differentiation by IS6110 RFLP or mixed-linker PCR are the methods of choice. A strong association was found between the results of different genetic markers, indicating a clonal population structure of M. tuberculosis strains. Several separate genotype families within the M. tuberculosis complex could be recognized on the basis of the genetic markers used.

Bacterial Typing Techniques↗

Analytical sensitivity, reproducibility of results, and clinical performance of five PCR assays for detecting Chlamydia pneumoniae DNA in peripheral blood mononuclear cells.

Chlamydia pneumoniae has been associated with atherosclerosis and coronary artery disease (CAD), and its DNA has been detected in atheromatous lesions of the aorta, carotid, and coronary arteries by a variety of PCR assays. The objective of this study was to compare the performances of five published PCR assays in the detection of C. pneumoniae in peripheral blood mononuclear cells (PBMCs) from patients with coronary artery disease. The assays included two conventional PCRs, one targeting a cloned PstI fragment and one targeting the 16S rRNA gene; two nested PCRs, one targeting the 16S rRNA gene and one targeting ompA; and a touchdown enzyme time release (TETR) PCR, targeting the 16S rRNA gene. All PCRs had similar analytical sensitivities and detected a minimum of 0.005 inclusion-forming units (IFU) of C. pneumoniae; the ompA nested PCR and the TETR PCR were slightly more sensitive and detected 0.001 IFU. Assay reproducibility was examined by testing 10 replicates of C. pneumoniae DNA by each assay. All five assays showed excellent reproducibility at high levels of DNA, with scores of 10 out of 10 for 0.01 IFU, but exhibited decreased reproducibility for smaller numbers of C. pneumoniae IFU for all tests. Pairwise comparison of test results indicated that there was a significant difference between tests (Cochran Q = 32.0, P<0.001), with the PstI fragment (P<0.001) and 16S rRNA (P = 0.002) assays having lower reproducibility than the nested ompA and TETR assays. To further analyze assay sensitivity, C. pneumoniae-infected U-937 mononuclear cells were added to whole blood, and extracted mononuclear-cell DNA was tested by each assay. All five assays showed similar sensitivities, detecting 15 infected cells; three assays detected 3 infected cells, while all assays were negative at the next dilution (1.5 infected cells). A striking difference in performance of the five assays was seen, however, when PBMCs from CAD patients were tested for C. pneumoniae DNA. The ompA nested PCR detected C. pneumoniae DNA in 11 of 148 (7.4%) specimens, the 16S rRNA nested PCR detected 2 positives among the 148 specimens (1.4%) (P<0.001), and the other 3 assays detected no positive specimens (P<0.001, compared with the ompA assay). These results indicate that analytical sensitivity alone does not predict the ability of an assay to detect C. pneumoniae in whole-blood-derived PBMCs. Before standardized assays can be used in wide-scale epidemiological studies, further characterization of these assays will be required to improve our understanding of their performance in the detection of C. pneumoniae in clinical material.

Bacterial Outer Membrane Proteins↗

Discriminatory power and reproducibility of novel DNA typing methods for Mycobacterium tuberculosis complex strains.

In recent years various novel DNA typing methods have been developed which are faster and easier to perform than the current internationally standardized IS6110 restriction fragment length polymorphism typing method. However, there has been no overview of the utility of these novel typing methods, and it is largely unknown how they compare to previously published methods. In this study, the discriminative power and reproducibility of nine recently described PCR-based typing methods for Mycobacterium tuberculosis were investigated using the strain collection of the interlaboratory study of Kremer et al. This strain collection contains 90 M. tuberculosis complex and 10 non-M. tuberculosis complex mycobacterial strains, as well as 31 duplicated DNA samples to assess reproducibility. The highest reproducibility was found with variable numbers of tandem repeat typing using mycobacterial interspersed repetitive units (MIRU VNTR) and fast ligation-mediated PCR (FLiP), followed by second-generation spoligotyping, ligation-mediated PCR (LM-PCR), VNTR typing using five repeat loci identified at the Queens University of Belfast (QUB VNTR), and the Amadio speciation PCR. Poor reproducibility was associated with fluorescent amplified fragment length polymorphism typing, which was performed in three different laboratories. The methods were ordered from highest discrimination to lowest by the Hunter-Gaston discriminative index as follows: QUB VNTR typing, MIRU VNTR typing, FLiP, LM-PCR, and spoligotyping. We conclude that both VNTR typing methods and FLiP typing are rapid, highly reliable, and discriminative epidemiological typing methods for M. tuberculosis and that VNTR typing is the epidemiological typing method of choice for the near future.

Bacterial Typing Techniques↗

Reproducibility of low galactomannan enzyme immunoassay index values tested in multiple laboratories.

The Platelia galactomannan enzyme immunoassay is a commercially available nonculture method for diagnosing invasive aspergillosis. Recently, steps have been taken to improve sensitivity; specifically, a low (0.5 to 0.7) galactomannan index (GMI) value to determine positivity has been validated by multiple groups. We evaluated the intra-assay and interassay reproducibility at low index levels using three different kit lots on three different days in three different microbiology laboratories. Clinical and spiked sera were blinded and sent with galactomannan enzyme immunoassay (EIA) kits to the participating laboratories. We also prospectively collected data on all galactomannan EIAs performed between 1 September 2003 and 21 July 2004 at the University of Washington Medical Center microbiology laboratory to assess reproducibility of clinical samples analyzed in "real time." From the multilaboratory study, a total of 836 results were available for evaluation. Reproducibility was excellent between laboratories and on different days. Significant variability was seen between runs/lots, which may in part be associated with different threshold control values in different kits. Among the 1,410 clinical samples that were prospectively analyzed, 168 (90%) were confirmed to be positive on repeat testing (GMI, > or =0.5). Among the 19 (10.2%) initially positive samples not confirmed on repeat testing, the majority had a GMI at the threshold of the assay (between 0.5 and 0.7). Our findings suggest that the Platelia galactomannan immunoassay has good reproducibility. However, changes in GMI levels when different kit lots are used, and single samples with low-positive (GMI of 0.5 to 0.7) indices, should be interpreted with caution.

Antigens, Fungal↗

Clinical signs of early osteoarthritis: reproducibility and relation to x ray changes in 541 women in the general population.

The definition and classification of early clinically apparent osteoarthritis both in clinical situations and in epidemiological surveys remains a problem. Few data exist on the between-observer reproducibility of simple clinical methods of detecting hand and knee osteoarthritis in the population and their sensitivity and specificity as compared with radiography. Two observers first studied the reproducibility of a number of clinical signs in 41 middle aged women. Good rates of agreement were found for most of the clinical signs tested (kappa = 0.54-1.0). The more reproducible signs were then tested on a population of 541 women, aged 45-65, drawn from general practice, screening centres, and patients previously attending hospital for non-rheumatic problems. The major clinical signs used had a high specificity (87-99%) and lower sensitivity (20-49%) when compared with radiographs graded on the Kellgren and Lawrence scale (2+ = positive). When analysis was restricted to symptomatic radiographic osteoarthritis, levels of sensitivity were increased and specificity was lowered. These data show that certain physical signs of osteoarthritis are reproducible and may be used to identify clinical disease. They are not a substitute for radiographs, however, if radiographic change is regarded as the 'gold standard' of diagnosis. As the clinical signs tested seemed specific for osteoarthritis they may be of value in screening populations for clinical disease.

Female↗

Reproducibility and accuracy of measurements with a hand held autorefractor in children.

AIM: To determine reproducibility and accuracy of the Nikon Retinomax autorefractor when used with children who were made cycloplegic. METHODS: Autorefraction and retinoscopy or subjectively refined retinoscopy (where, under the patient's direction, the refraction was varied until the best visual acuity was achieved) were performed on the right eye of 47 children, age 11-93 months. Autorefraction was performed using the Nikon Retinomax, which provides up to eight measured values of refractive error and one representative measurement of refractive error. RESULTS: Autorefractor measurements were successfully obtained from 7/9 children age 3 years or younger, and from all older children. Vector methods were used to calculate differences. Retinomax reproducibility averaged 0.43 D. Unbiased Retinomax and retinoscopy measurements differed by an average of 0.82 D. Unbiased Retinomax and subjectively refined retinoscopy differed by an average of 1.03 D. CONCLUSIONS: Reproducibility of Retinomax measured values in children is comparable with reproducibility of retinoscopy, subjective refraction, and autorefraction measurements in adults. Agreement between Retinomax and retinoscopy and agreement between Retinomax and subjective refinement in children is comparable with agreement between autorefraction and subjective refraction in adults. The study indicates that the Retinomax is a useful instrument for measuring refractive errors in young children.

Child↗

Reproducibility of topographic measures of the glaucomatous optic nerve head.

AIMS/BACKGROUND: Laser scanning tomography provides an assessment of three dimensional optic disc topography. For the clinical purpose of follow up of glaucoma patients, the repeatability of the various measured variables is essential. In the present study, the reproducibility of morphometric variables calculated by the topographic scanning system, TopSS (Laser Diagnostic Technology, San Diego, CA) was investigated. METHODS: Two independent measurements (30 minutes apart) each consisting of three complete images of the optic disc were performed on 16 eyes of 16 glaucoma patients using a TopSS. The instrument calculates 14 morphometric variables for the characterisation of the optic disc. RESULTS: From the two tailed paired tests, all variables were seen to have good reproducibility. However, correlation and regression analyses showed that only the three variables, volume below, half depth area, and average cup depth, are acceptably reproducible. CONCLUSION: The TopSS provides three variables which describe the physiological shape of the optic disc that have high reproducibility. These three variables might be useful for following the progression of optic disc changes in glaucoma patients.

Aged↗

Reproducibility of volumetric measurements of normal maculae with the Heidelberg retina tomograph.

AIMS: The Heidelberg retina tomograph (HRT) is a scanning laser ophthalmoscope with confocal optics. The reproducibility of the optic nerve head topography is accurate and reliable. The authors describe a new technique for the assessment of macular thickening by volumetric quantification and present the results of its reproducibility in normal subjects. METHODS: Topographic images of the macula, centred on the fovea were obtained in one eye of 44 normal subjects. The volumes above the reference plane bound by a 1 mm, 2 mm, and 3 mm diameter circle were measured. The reference plane was adjusted to the lowest point of the height variation of the contour line at each examination. The reproducibility of repeated measurements within a 2 mm diameter circle was assessed in 20 eyes selected at random. Three HRT scans of each eye were obtained. The measurements of volume above reference plane of each scan were repeated three times on three separate days. RESULTS: The intrascan coefficients of variability measured 7.12-9.57%. The 95% confidence interval for the geometric mean ratio of single volume measurements was 0.92 to 1.24 for scans 1 and 2, 0.89 to 1.17 for scans 1 and 3, and 0.81 to 1.12 for scans 2 and 3. When the mean of three measurements of one scan were compared with the mean of three measurements of a second scan, the 95% confidence interval for their geometric mean ratio was 0.89 to 1.20 for scans 1 and 2, 0.89 to 1.16 for scans 1 and 3, and 0.84 to 1.13 for scans 2 and 3. The average standard deviation (SD) for one measurement per scan was 0.02 mm3, and 0.019 mm3 for two or three measurements per scan. Linear regression demonstrated a significant increase in SD as volumetric measurements increased (p = 0.003). Age did not significantly affect the SD of volumetric measurements (p = 0.797). The authors found no significant differences in volumetric measurements across all ages for all three circles (p = 0.314, p = 0.471, p = 0.267). CONCLUSION: Good reproducibility for volumetric measurements at the macula was found with the HRT using the above technique in normal subjects. This method may be extremely useful for the identification and quantification of diabetic macular oedema and for monitoring the effects of argon laser photocoagulation.

Adult↗

Reproducibility and responsiveness of quality of life assessment and six minute walk test in elderly heart failure patients.

OBJECTIVE: To examine the reproducibility and responsiveness to change of a six minute walk test and a quality of life measure in elderly patients with heart failure. DESIGN: Longitudinal within patient study. SUBJECTS: 60 patients with heart failure (mean age 82 years) attending a geriatric outpatient clinic, 45 of whom underwent a repeat assessment three to eight weeks later. MAIN OUTCOME MEASURES: Subjects underwent a standardised six minute walk test and completed the chronic heart failure questionnaire (CHQ), a heart failure specific quality of life questionnaire. Intraclass correlation coefficients (ICC) were calculated using a random effects one way analysis of variance as a measure of reproducibility. Guyatt's responsiveness coefficient and effect sizes were calculated as measures of responsiveness to change. RESULTS: 24 patients reported no major change in cardiac status, while seven had deteriorated and 14 had improved between the two clinic visits. Reproducibility was satisfactory (ICC > 0.75) for the six minute walk test, for the total CHQ score, and for the dyspnoea, fatigue, and emotion domains of the CHQ. Effect sizes for all measures were large (> 0.8), and responsiveness coefficients were very satisfactory (> 0.7). Effect sizes for detecting deterioration were greater than those for detecting improvement. CONCLUSIONS: Quality of life assessment and a six minute walk test are reproducible and responsive measures of cardiac status in frail, very elderly patients with heart failure.

Aged↗

Reproducibility of non-specific bronchial challenge in adults: implications for design, analysis and interpretation of clinical and epidemiological studies.

BACKGROUND: Poor reproducibility of an outcome measure reduces power and, in an independent variable, biases results. The intraclass correlation coefficient measures loss of power and degree of bias. Information is lacking on the intraclass correlation coefficient for bronchial responsiveness and factors affecting reproducibility. METHODS: Papers containing information on reproducibility of bronchial responsiveness were identified using a Medline search and citations. Within and between person components of variance of PD20 or PC20 were expressed in doubling dose or concentration units, and the intraclass correlation coefficient calculated when not reported. RESULTS: Results were extracted from 32 papers. Intraclass correlation coefficients were over 0.9 in short term studies of highly selected asthmatic patients, but larger and most long term studies had lower intraclass correlation coefficients, less than 0.5 in some cases, due to greater within person or lower between person variation. Reproducibility of dose or concentration-response slope was generally higher, but still less than that of forced expiratory volume in 1 second. CONCLUSIONS: Information is available to calculate sample size for studies with bronchial responsiveness as the outcome, but results when bronchial responsiveness is an explanatory variable may be misleading.

Adult↗

Breath-hold FLASH and FISP cardiovascular MR imaging: left ventricular volume differences and reproducibility.

PURPOSE: To compare fast imaging with steady-state precession (FISP) and fast low-angle shot (FLASH) magnetic resonance acquisitions to quantify left ventricular volumes, mass, and function and to determine if the two techniques are comparable. MATERIALS AND METHODS: Left ventricular volume studies were performed in 10 patients with heart failure and in 10 healthy subjects by using FISP and FLASH imaging. Identical section positions were used for section-by-section contour comparisons. Manual analysis was performed by two experienced observers. The study was repeated on a different day and interobserver and interstudy reproducibility assessed. RESULTS: With FISP, end-diastolic volume was larger (healthy subjects: +18 mL [13%], P <.001; patients: +6 mL [3%], not significant), end-systolic volume larger (healthy subjects: +9 mL [17%], P =.001; patients: +8 mL [6%], P =.001) and left ventricular mass smaller (healthy subjects: -25 g (19%), P <.001; patients: -21 g (11%), P <.001). There were no significant differences in ejection fraction. Both sequences had excellent interstudy and interobserver reproducibility, with statistically better reproducibility for interstudy healthy-subject ejection fraction on FISP images (P =.05). Section-by-section analysis determined that at FISP, endocardial contours were drawn larger and the epicardial contours smaller than on FLASH images. FISP enabled better delineation of epicardial fat from myocardium, of blood-myocardium interface in areas of trabeculation or papillary muscles, and of the atrioventricular ring. CONCLUSION: FISP produces small but significantly higher left ventricular volume measurements, as compared with FLASH imaging. FLASH imaging and FISP have similar reproducibility.

Adult↗

Relative cerebral blood volume measurements in intracranial mass lesions: interobserver and intraobserver reproducibility study.

PURPOSE: To assess inter- and intraobserver reproducibility for different techniques of measuring relative cerebral blood volume (rCBV) in patients with intracranial mass lesions. MATERIALS AND METHODS: Three independent observers (neuroradiology fellows) who were blinded to the histopathologic diagnosis performed rCBV measurements in 50 patients with various intracranial mass lesions. Three different methods were compared. With method 1, placement of a single region of interest was guided by a color overlay map. With methods 2 and 3, the highest rCBV value and the mean of repeated rCBV measurements, respectively, were recorded. Calculations of the intraclass correlation coefficient, coefficient of variation (CV), and descriptive statistics were used to determine the levels of reproducibility. A multiple linear regression model was used to evaluate for possible explanatory factors for interobserver variance. RESULTS: Method 2 had, overall, the best reproducibility of all techniques, with an intraclass interobserver correlation coefficient of 0.71 (indicating good agreement), interobserver CV of 30%, and intraobserver CV in the range of 32%-41%. Measurement variations between observers correlated significantly (P <.001) with increasing rCBV values. CONCLUSION: In this study, interobserver and intraobserver reproducibility of rCBV measurements were clinically acceptable.

Adolescent↗

Mammography with computer-aided detection: reproducibility assessment initial experience.

PURPOSE: To examine the performance and reproducibility of a commercially available computer-aided detection (CAD) system with a set of mammograms obtained in 100 patients who had undergone biopsy after positive findings at mammography. MATERIALS AND METHODS: One hundred positive mammographic examinations (four views each), depicting 96 masses and 50 microcalcification clusters, were scanned and analyzed three times by the CAD system. Reproducibility of detection sensitivity and the individual CAD-generated cues in the three images were examined. Both abnormality- and region-based detection sensitivities were compared. RESULTS: Forty-eight (96.0%) of 50 microcalcification clusters were marked on all three images in the abnormality-based analysis. Of the remaining two clusters, one was marked in two images and one was marked in only one. The abnormality-based sensitivity for mass detection ranged from 66.7% (64 of 96) to 70.8% (68 of 96). The system generated identical patterns (including images with and those without cues) for all three images in 53.3% (213 of 400) of images. For true-positive cluster regions, 88.9% (80 of 90) were marked at the same location in all images. For true-positive mass regions, 69.5% (82 of 118) were marked at the same locations in all images. In false-positive detections, only 44.0% (81 of 184) of false-positive mass regions and 31.9% (38 of 119) of false-positive cluster regions were marked at the same locations on all three images. CONCLUSION: Reproducibility of marked regions generated by the CAD system is improved from that reported previously, largely as a result of the substantial reduction in the false-positive detection rates. Reproducibility of true-positive identification of masses remains an important issue that may have methodologic and clinical practice implications.

Biopsy↗

Effect of endocardial trabeculae on left ventricular measurements and measurement reproducibility at cardiovascular MR imaging.

PURPOSE: To prospectively assess the effect of including or excluding endocardial trabeculae in left ventricular (LV) measurements and the reproducibility of these measurements at cine cardiovascular magnetic resonance (MR) imaging with true fast imaging with steady-state precession (FISP). MATERIALS AND METHODS: The study was approved by the local ethics committee, and each subject gave informed consent before participating. Twenty healthy subjects and 20 consecutive patients underwent 1.5-T cardiovascular MR imaging. Seven to 12 short-axis views encompassing the entire LV were acquired by using true FISP. Endocardial and epicardial contours were traced manually. The data sets in each patient were analyzed twice: with inclusion of endocardial trabeculae in the LV cavity volume and with exclusion of endocardial trabeculae from the cavity volume. On the basis of these two contour sets, the end-diastolic (ED) and end-systolic (ES) LV volumes, ejection fraction (EF), and LV mass were calculated. Additionally, interobserver and interexamination reproducibility was assessed by using Bland-Altman analysis. RESULTS: Compared with exclusion of trabeculae, inclusion of trabeculae in the LV cavity volume resulted in significantly larger ED and ES LV volumes (mean differences, 21 mL +/- 11 [standard deviation] and 19 mL +/- 33, respectively; P < .001) and lower EFs (mean difference, -2% +/- 2; P < .001). The calculated LV mass was significantly smaller with inclusion than with exclusion of trabeculae (mean difference, -21 g +/- 12; P < .001). All interobserver and interexamination limits of agreement based on inclusion of trabeculae, except those for EF measurements, were superior to those based on exclusion of trabeculae. At measurement reproducibility comparisons, differences in interobserver ED LV volume and LV mass and interexamination LV mass were statistically significant, favoring the inclusion of trabeculae in the LV cavity volume. CONCLUSION: Trabeculae significantly affect quantifications of LV volume and mass. The superior reproducibility of LV measurements with the inclusion of endocardial trabeculae in the cavity volume favors this tracing algorithm for clinical use.

Adult↗

Left ventricular measurements with cine and spin-echo MR imaging: a study of reproducibility with variance component analysis.

The authors studied the reproducibility of repeated measurements of left ventricular volumes, weight, and wall stress as determined with cine and spin-echo magnetic resonance (MR) imaging. Two observers analyzed 40 serial MR imaging examinations twice, yielding a total of 160 repeated measurements. Estimates of 95% ranges for change were ejection fraction, 10% and 12%; wall mass, 16% and 21%; and wall stress, 22% and 20%, for measurements derived from cine MR imaging and spin-echo MR imaging, respectively. Reproducibility was not significantly different between cine and spin-echo MR imaging. Intraobserver, interobserver, and interexamination errors were quantitated with variance component analysis. Interexamination variability was the single most important contributor to total variance. Reproducibility of left ventricular chamber volume measurements with MR imaging is superior to that of other imaging modalities. In addition, MR imaging can provide reliable estimates of wall mass and wall stress. Efforts to improve reproducibility should be aimed at lowering interexamination variability.

Adult↗

Early stage melanoma: lymphoscintigraphy, reproducibility of sentinel node detection, and effectiveness of the intraoperative gamma probe.

PURPOSE: To assess the influence of lymphoscintigraphic and intraoperative gamma probe findings on the surgical management of melanoma and to test reproducibility of lymphoscintigraphic findings. MATERIALS AND METHODS: After lymphoscintigraphic identification of the sentinel node, intraoperative gamma probe localization and sentinel lymph node excision were performed in 25 patients. To assess reproducibility, 13 patients underwent lymphoscintigraphy twice within 2-17 days. A modified preparation of technetium-99m sulfur colloid with smaller particles than routinely obtained was injected intradermally around the lesion. Dynamic flow images were obtained at 10 seconds per frame followed by a series of static images obtained every 5 minutes for 30 minutes. RESULTS: A sentinel node was identified in all patients. In eight patients, multiple drainage pathways were seen and surgical management was changed. In 11 of the 13 who underwent lymphoscintigraphy twice, sentinel node identification was reproducible. CONCLUSION: Lymphoscintigraphy is reproducible in detection of the sentinel node and with the surgical probe helps effectively guide surgical management.

Female↗

Constant infusion and bolus injection of stable-label tracer give reproducible and comparable fasting HGO.

We have investigated the reproducibility of fasting hepatic glucose output (HGO) estimates by use of isotope dilution methodology of stable-label tracers. Six normal subjects were studied on two occasions 1 wk apart. After an overnight fast, the subjects received a bolus injection of 7 mg/kg of [U-13C]glucose and, simultaneously, a primed constant infusion of 0.05 mg.kg-1.min-1 of [6,6(-2)H]glucose. The bolus injection provided one estimate of HGO (HGOBOL), and the constant infusion provided two estimates of HGO, namely, HGO at 2 h (HGOINF2) and HGO at 4 h (HGOINF4), both with the assumption of steady-state conditions. All estimates were similar in value; HGOBOL was highest, followed by HGOINF2 and HGOINF4 [2.30 +/- 0.11 (SE), 2.17 +/- 0.12, and 2.01 +/- 0.13 mg.kg-1.min-1]. The constant infusion gave highly reproducible results. In the case of HGOINF2, the within-subject coefficient of variation (CV) was only 3% compared with 5% of HGOINF4. The reproducibility of HGOBOL was comparable with the within-subject CV of 7%. We conclude that a constant infusion and a bolus injection of stable-label tracer give reproducible and comparable estimates of HGO.

Adult↗