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Comparison between reproducibility and sensitivity of muscle sympathetic nerve traffic and plasma noradrenaline in man.

1. Although plasma noradrenaline and muscle sympathetic nerve traffic have been shown to be suitable markers of sympathetic activity in man, no study has systematically compared the reproducibility and sensitivity of these two indices of adrenergic tone. 2. Reproducibility data were collected in 10 subjects, in whom plasma noradrenaline was assessed by HPLC on blood samples withdrawn from an antecubital vein and efferent postganglionic muscle sympathetic nerve activity was measured by microneurography from a peroneal nerve, together with arterial blood pressure (Finapres technique). Measurements were obtained in a first session (session 1), 60 min later (session 2) and after 14 days (session 3). While muscle sympathetic nerve activity values recorded in the three different experimental sessions were closely and significantly correlated with each other (r always > 0.90, P < 0.001), noradrenaline showed a less significant correlation between sessions 1 and 2 (r = 0.71, P < 0.05) or no correlation between sessions 1 and 3 (r = 0.45, P not significant). 3. Sensitivity data were collected by evaluating muscle sympathetic nerve activity and noradrenaline values in three different age groups (young, middle-age and old subjects, n = 18), in three groups with different blood pressures (normotensive, mild and severe hypertensive subjects, n = 30) and in a group of eight subjects before and after a physical training programme, i.e. conditions known to increase or reduce sympathetic cardiovascular drive. Muscle sympathetic nerve activity was significantly increased by aging and hypertension, and reduced by physical training. The noradrenaline changes were much less marked and consistent. 4. These data suggest that muscle sympathetic nerve activity has a greater short- and medium-term reproducibility than noradrenaline. In several conditions known to modify sympathetic cardiovascular drive muscle sympathetic nerve activity also appears to change more clearly than noradrenaline.

Adolescent↗

Interstudy reproducibility of right ventricular volumes, function, and mass with cardiovascular magnetic resonance.

BACKGROUND: Cardiovascular magnetic resonance (CMR) has shown excellent results for interstudy reproducibility in the assessment of left ventricular (LV) parameters. However, interstudy reproducibility data for the more complex-shaped right ventricle in a large study group have not yet been reported. We sought to determine the interstudy reproducibility of measurements of right ventricular (RV) volumes, function, and mass with CMR and compare it with correspondent LV values. METHODS: Sixty subjects (47 men; 20 healthy volunteers, 20 patients with heart failure, 20 patients with ventricular hypertrophy) underwent 2 CMR studies for assessment of RV measurements with a minimum time interval between each study. RESULTS: The overall interstudy reproducibility (range between groups) for the RV was 6.2% (4.2%-7.8%) for end-diastolic volume, 14.1% (8.1%-18.1%) for end-systolic volume, 8.3% (4.3%-10.4%) for ejection fraction (EF), and 8.7% (7.8%-9.4%) for RV mass. RV reproducibility was not as good as for the LV for all measures in all 3 groups, but this was only statistically significant for EF (P <.01). CONCLUSIONS: CMR showed good interstudy reproducibility for RV function parameters in healthy subjects, patients with heart failure, and patients with hypertrophy, which suggests that CMR is reliable for serial RV assessment. These data can be used to power sample sizes for longitudinal research studies of RV volume and function. The reproducibility values were similar to, but generally lower than, the reproducibility values for the LV in the same study population, which indicates that sample sizes for RV studies are in general larger than those for LV studies.

Adult↗

[Minimal invasiveness of laparoscopic radical prostatectomy: reality or dream?].

Currently, radical retropubic prostatectomy is the standard procedure for clinically localized prostate cancer. The surgical technique has been continuously refined for decades, resulting in reduced morbidity and improved functional and oncologic results. Since the late 90s, radical prostatectomy has been increasingly performed laparoscopically. A search of the available data has found that the articles published so far have proven the feasibility of the laparoscopic procedure but never confirmed its less invasiveness. In accordance with previous studies that have evaluated the invasiveness of various open and laparoscopic procedures, our clinic, which has routinely performed both techniques for several years, addressed the question whether laparoscopic prostatovesiculectomy indeed induces less severe surgical trauma. This prospective nonrandomized comparison study of the University Clinic of Urology at the Martin-Luther University at Halle-Wittenberg recruited a total of 64 patients, who underwent laparoscopic radical prostatectomy (n = 32) or open retropubic prostatectomy (n = 32) from January 2003 to April 2004. Both patient groups were comparable as to preoperative staging, PSA value and Gleason score. Besides perioperative parameters, such as surgical time, intra- and postoperative complications, blood loss and transfusion rate, need for analgetics and length of hospital stay, the comparison included oncologic data, such as Gleason score, pathologic stage and numbers of positive specimen margins. To get objectively reproducible data, the range of the systemic answers concerning the surgically induced tissue trauma was recorded as laboratory data. In all patients, pre-, intra-, and postsurgical markers of the acute-phase C-reactive protein, serum amyloid A (SAA), interleukin-6 (IL-6) and interleukin-10 (IL-10) were measured. The transfusion rate was 6 % for laparoscopic prostatectomies and 12 % for open prostatectomies. A rectal tear had to be intraoperatively repaired in one laparoscopically operated patient. The postoperative use of analgetics was comparable in both groups. The median hospital stay was 12.4 days for the laparoscopic and 11.2 days for the open surgical group. For T2 tumors, positive specimen margins were found in 6 cases (17 %) of the laparoscopic and in 4 cases (12 %) of the open surgical group. As to the indicators of any systemic reaction, no significant difference could be found during the entire clinical course between both surgical methods. In comparison with patients who underwent conventional open prostatectomy, patients with laparoscopically radical prostatectomy had identical to slightly higher serum levels of the acute-phase parameters, as evidence of an equal or a discretely manifested systemic response to the surgical trauma. The so far assumed less invasiveness of laparoscopic radical prostatectomy is not objectively supported by the data from this study. Thus, surgical trauma and its linked invasiveness must be considered equal for both methods, at least for the time being.

Adult↗

Repeatability and reproducibility of retention data and band profiles on reversed-phase liquid chromatography columns. IV. Results obtained with Luna C18 (2) columns.

The reproducibility of retention data and band profile characteristics was investigated for a series of columns packed with Luna C18 (2), a silica-based, reversed-phase adsorbent. High precision data were obtained and statistically compared among five columns from the same batch (column-to-column reproducibility) and nine columns from as many different batches (batch-to-batch reproducibility). These data were acquired under five different sets of chromatographic conditions, for a group of 30 neutral, acidic, and basic compounds selected as probes following an experimental protocol previously described. This work is part of a study on the precision of chromatographic analyses. Its purpose is to illustrate the contribution of the stationary phase reproducibility to this precision.

Chromatography, Liquid↗

A UK-based investigation of inter- and intra-observer reproducibility of Gleason grading of prostatic biopsies.

AIMS: The frequency of prostatic core biopsies to detect cancer has been increasing with more widespread prostate specific antigen (PSA) testing. Gleason score has important implications for patient management but morphological reproducibility data for British practice are limited. Using literature-based criteria nine uropathologists took part in a reproducibility study. METHODS: Each of the nine participants submitted slides from consecutive cases of biopsy-diagnosed cancer assigned to the Gleason score groups 2-4, 5-6, 7 and 8-10 in the original report. A random selection of slides was taken within each group and examined by all pathologists, who were blind to the original score. Over six circulations, new slides were mixed with previously read slides, resulting in a total of 47 of 81 slides being read more than once. RESULTS: For the first readings of the 81 slides, the agreement with the consensus score was 78% and overall interobserver agreement was kappa 0.54 for Gleason score groups 2-4, 5-6, 7, 8-10. Kappa values for each category were 0.33, 0.56, 0.44 and 0.68, respectively. For the 47 slides read more than once, intra-observer agreement was 77%, kappa 0.66. The study identified problems in core biopsy interpretation of Gleason score at levels 2-4 and 7. Patterns illustrated by Gleason as 2 tended to be categorized as 3 because of the variable acinar size and unassessable lesional margin. In slides with consensus Gleason score 7, 13% of readings were scored 6 and in slides with consensus 6, 18% of readings were scored 7. CONCLUSIONS: Recommendations include the need to increase objectivity of the Gleason criteria but limits of descriptive morphology may have to be accepted.

Biopsy↗

Microarray analysis of gene expression in lupus.

Recent advances in the study of global patterns of gene expression with the use of microarray technology, coupled with data analysis using sophisticated statistical algorithms, have provided new insights into pathogenic mechanisms of disease. Complementary and reproducible data from multiple laboratories have documented the feasibility of analysis of heterogeneous populations of peripheral blood mononuclear cells from patients with rheumatic diseases through use of this powerful technology. Although some patterns of gene expression, including increased expression of immune system cell surface activation molecules, confirm previous data obtained with other techniques, some novel genes that are differentially expressed have been identified. Most interesting is the dominant pattern of interferon-induced gene expression detected among blood mononuclear cells from patients with systemic lupus erythematosus and juvenile dermatomyositis. These data are consistent with longstanding observations indicating increased circulating interferon-alpha in the blood of patients with active lupus, but draw attention to the dominance of the interferon pathway in the hierarchy of gene expression pathways implicated in systemic autoimmunity.

Animals↗

The anxiety thermometer: a validation study.

The aim of our study was to provide validation and reproducible data for the anxiety thermometer. This thermometer is either a continuous or a 10-point Likert-type scale on which subjects are asked to rate their anxiety feelings at a particular moment. It is a quick way to measure state-anxiety. As a validation criterion the State-Trait Anxiety Inventory (STAI) A-State scale was used. To test the reproducibility of the thermometer, a test-retest correlation coefficient was calculated, with a retrospective second thermometer score. The ego-threatening situation used was a written examination. Two experiments were carried out during different examination conditions. The data consistently indicated that the validity and reproducibility of the anxiety thermometer is fair (correlation coefficients between .60 and .78) In the second study, the possible influence of two factors on the retrospective scores were additionally tested.

Adult↗

Effects of the structure of a toxicokinetic model of butadiene inhalation exposure on computed production of carcinogenic intermediates.

A flow-limited physiologically based toxicokinetic model was constructed for uptake, metabolism, and clearance of butadiene (BD) and its principal metabolite 1,2-epoxy-3-butene (EB), using physiological and biochemical parameters from the literature where available. The model includes compartments for blood, liver, lung, fat, GI tract, other rapidly perfused tissues, and slowly perfused tissues. The blood was distributed among compartments for arterial plus venous blood and subcompartments for vascular spaces associated with each of the tissue compartments. The lung contained a subcompartment for the alveolar space. Metabolic activation of BD by cytochrome P450-catalyzed epoxidation was modeled as occurring in liver, lung, and the rapidly perfused tissue compartments. The detoxication of EB catalyzed by epoxide hydrolase and glutathione S-transferase (GST) was modeled as occurring in liver, lung, and the rapidly perfused tissues compartments and by blood GST activity. The model also includes depletion of glutathione (GSH) by GST-catalyzed conjugation of EB and 3-butene-1,2-diol and resynthesis of GSH from cysteine. Values of biochemical parameters that were unavailable in the literature were estimated by iteratively reweighted least squares optimization to reproduce data for uptake of BD and EB by rats and mice in closed chambers. The resulting model also reproduced the depletion of GSH in liver and lung in flow-through systems. It reproduced the concentrations of expired EB produced from BD in closed chambers but overpredicted separately measured blood EB concentrations in flow-through systems, indicating an inconsistency between these two experiments that cannot be resolved by this model or an inadequacy in the model. Equilibration of chamber gases with the alveolar space and alveolar gas with lung capillary blood results in much less dilution of the inhaled gas in the blood compared with the predictions of models in which chamber gas equilibrates directly with the total circulation. The production of EB predicted by the present model was found to be sensitive to a number of physiological and biochemical parameters. A valid and useful toxicokinetic model must have reliable physiological and enzymological data for BD biotransformation before it can be credibly used for human risk assessment.

Administration, Inhalation↗

Pharmacokinetics of different doses of methotrexate at steady state by in situ microdialysis in a rat model.

We used a microdialysis technique to monitor extracellular methotrexate (MTX) levels during the steady state in a rodent model. Microdialysis probes were implanted in the muscle, liver, and kidney of anesthetized male Wistar rats. MTX (18.75-500 mg/kg) was given as a continuous infusion through a venous catheter, and blood samples were obtained through a second venous catheter. Heparinized plasma, ultrafiltered plasma, microdialysis effluent from tissues, and tissue samples (obtained at the end of experiments) were analyzed for MTX content by high-performance liquid chromatography (HPLC). Steady state was demonstrated in the blood and tissues from 2 h until the end of the experiments (6 h). Extracellular drug levels in muscle and liver displayed a linear correlation with doses, whereas kidney levels reached a plateau at an MTX dose of 150 mg/kg per 6 h. Microdialysis-fluid endpoint levels for muscle, liver, and kidney were positively correlated to the endpoint total tissue levels (r2 = 0.80, 0.85, and 0.68, respectively). In the kidneys, the maximal relative tissue MTX accumulation was measured at a total dose of 75 mg/kg per 6 h. At higher doses, the relative drug sequestration declined to less than half of the values observed at this dose. This study demonstrates that the microdialysis technique can provide reproducible data on MTX tissue exposure in an animal model and that it offers a means of serial and reproducible monitoring of extracellular-tissue MTX levels at steady state and over a wide dose range. Pending additional studies, microdialysis may be a helpful technique for elucidating the kinetics of drug delivery to both targeted and toxicity-prone tissues during chemotherapy.

Animals↗

Understanding normal and impaired word reading: computational principles in quasi-regular domains.

A connectionist approach to processing in quasi-regular domains, as exemplified by English word reading, is developed. Networks using appropriately structured orthographic and phonological representations were trained to read both regular and exception words, and yet were also able to read pronounceable nonwords as well as skilled readers. A mathematical analysis of a simplified system clarifies the close relationship of word frequency and spelling-sound consistency in influencing naming latencies. These insights were verified in subsequent simulations, including an attractor network that accounted for latency data directly in its time to settle on a response. Further analyses of the ability of networks to reproduce data on acquired surface dyslexia support a view of the reading system that incorporates a graded division of labor between semantic and phonological processes, and contrasts in important ways with the standard dual-route account.

Dyslexia↗

Cervical motion in patients with chronic disorders of the cervical spine: a reproducibility study.

STUDY DESIGN: Test-retest of cervical motion in patients with chronic disorders of the cervical spine. OBJECTIVES: To determine the reproducibility of cervical motion and examine the feasibility of its representation by a single parameter. SUMMARY OF BACKGROUND DATA: Reproducibility of cervical motion findings has been largely limited to normal subjects, leaving a conspicuous void regarding the measurement error in clinical groups. METHODS: There were 2 groups of 25 chronic patients with whiplash and degenerative changes of the cervical spine tested twice (4-7 days). Head movement was measured along the 6 directions, as well as during rotation out of flexion and extension (cervical degenerative changes only). RESULTS: Compared to normal subjects, both groups had a 25% to 35% reduction in cervical motion. High intraclass correlation coefficients (ICCs) (range 0.8-0.92) were derived for all directions. The ICCs for rotation out of flexion and extension were low. The relative standard error of measurement ranged from 15% to 28% for all directions, whereas the corresponding scores of the total cervical motion excursion were 10.6 (cervical degenerative changes) and 13.6% (whiplash). CONCLUSIONS: Judged by the ICCs cervical motion, findings were reproducible. However, in view of the measurement error as well as the homogenous reductions, total cervical range of motion should be considered a suitable parameter for interpretation of cervical motion limitations in these patients.

Adult↗

Syringing as a method of cell dispersal. I. Effect on intermediate and superficial squamous cells.

Mechanical shear in the form of syringing was applied to human gynecologic cytology specimens in an effort to disperse cell clumps. The percentage of single squamous cells achieved with the optimum conditions is generally 70 to 100 per cent. Syringing with a constant pressure device produces a high yield of single squamous cells without the concurrent high cell loss as often observed using enzymatic or chemical procedures. Data presented demonstrate that the slide preparation and clump evaluation procedures used for this study yield reliable and reproducible data. Studies varying stroke number and plunger pressure were completed and conditions for maximum dispersal were established.

Cell Separation↗

Determining a detectable threshold of signal intensity in cDNA microarray based on accumulated distribution.

In microarray data mining, one of the key problems is how to handle weak signals. Based on a bent piecewise linear accumulated distribution generally found in the microarray data, a new detectable threshold finding method is proposed to filter genes with unreliable information in this paper. More reliable and reproducible data is produced for the subsequent data mining.

DNA, Complementary↗

Campylobacter and fluoroquinolones: a bias data set?

There is no universally accepted standard method for the isolation of Campylobacter spp. and it is considered that currently available isolation media are not yet optimal for the recovery of Campylobacter spp. from a range of sample types. Almost all methods incorporate antibiotics into the isolation media to inhibit growth of other bacteria within the sample. It is established that the incorporation of such antibiotics into isolation media will inhibit the growth of some Campylobacter spp. as well as other bacteria. The results of the use of such suboptimal isolation methods are that the isolates which 'survive' the isolation procedure will be those which: (i) are able to 'out compete' the rest of the bacteria in the sample, i.e. they are able to grow faster; (ii) are resistant to the antibiotics used in the isolation media; and (iii) are randomly selected by the laboratory technician as being a 'typical'Campylobacter spp. It is clear that such a procedure is intrinsically biased and will mean that species resistant to the antibiotics used in the media will be isolated. This introduces real doubt that the bacteria isolated are truly representative of those initially found on the sample. It is also becoming clear that Campylobacter spp. are rather difficult to isolate as pure cultures and many are in fact mixtures of more than one strain. Again this introduces great uncertainty as to the prevalence and distribution of respective species from the different sample types. This is especially true when considering isolation of Campylobacter spp. causing disease in man as there is no certainty that the selected isolate is that which was responsible for disease. The incorporation of antibiotics into the isolation media not only introduces the issue of species bias but perhaps more importantly exposes the Campylobacter spp. to a cocktail of antibiotics thereby providing the potential for them to 'switch on' antibiotic resistance mechanisms. It might be argued that this has always been the case for isolation of Campylobacter spp., however, we know that the antibiotic cocktails used in media over the last 10 years have changed and indeed there was a time when the filtration protocol which didn't use antibiotics was more widely used. As most reports in the literature do not state what methods were used to isolate Campylobacter spp. it is not possible to quantify any relationship between antibiotics used in the isolation media and susceptibility data. An approved method for Campylobacter susceptibility testing was not available until May 2002, all data generated prior to this date will have been generated using non-standard methods. As tremendous variability in the reproducibility data for Campylobacter spp. was observed during the development of the standard agar dilution susceptibility method, data generated with disk diffusion and broth microdilution methods must be considered with caution. It has been shown that, compared with the conventional agar dilution method, the E-test tends to give rise to lower minimal inhibitory concentrations (MICs) for sensitive strains and higher MICs for resistant strains. There are no recommended antibiotic breakpoint concentrations for Campylobacter spp. A breakpoint is used to separate sensitive from resistant strains of bacteria and is thus crucial to any discussion of antibiotic resistance. This discussion is further complicated by introduction of the terms microbiological and clinical breakpoints. While a microbiological breakpoint can be a useful parameter with regard to identifying resistance factors it cannot on its own be used to predict whether that bacteria will respond to treatment from an appropriate antibiotic. Predicting clinical response is a function of the clinical breakpoint which considers the pharmacokinetic profile of the antimicrobial compound, i.e. the concentration of the antimicrobial compound in the body and the MIC. The National Committee for Clinical Laboratory Standards (NCCLS) uses microbiological, pharmacokinetic and clinical data to establish breakpoints, without c and clinical data to establish breakpoints, without such considerations it is not possible to consider what is truly clinically sensitive and resistant. There are no reported studies that have systematically determined appropriate breakpoints for Campylobacter, there are data however, which relate MICs to clinical outcome. It is without dispute that microbiological resistance in Campylobacter spp. occurs as a result of mutation in the gyrA gene with single point mutations most frequently causing a four- to eightfold shift in the MIC. What is also clear is that if a high enough concentration of antimicrobial relative to MIC of the infecting organism can be achieved not only will the parent organism be killed but also the 'resistant' mutant. Considering the above and the concentrations of ciprofloxacin achieved in the gastro-intestinal tract it is not surprising that clinical cure can be demonstrated for organisms with an MIC of 32 microg ml(-1).

Animals↗

An Attempt to Interpret the Spread of Element Concentration in Antarctic Surface Snow: The Same Element in a Given Test Field, Several Elements in Different Sampling Fields

Sampling surface snow on a large test field always leads to a spread of analyte concentration data which partly follows a Gaussian distribution and partly a rectangular one as can be observed from the analysis of literature data. The spread depends on the nonuniformity of the air-snow interface in the field and on the extent of reproducibility of all the procedures used from sampling to analysis. Consequently a sample relevant to a restricted surface might be poorly representative of the surrounding area. Contamination of the sample during the gathering and storing steps is assumed to be the main source of nonrandom results (outliers). Using various statistical tools we were able to evaluate which part of the spread was due to the snow surface nonuniformity in the case of many samples collected in the same test field. In the case of samples gathered in different geographical areas, the possibility of finding correlations among points is greatly enhanced when three or more analytes are considered for each sample. When the same correlation is found for some analytes and a variable tentatively tested, information can be gained about the source of chemical content of snow samples. The use of UV pretreatment of snow samples has been proven to cut down the interference of organics on the electrochemical process in DPASV, allowing one to obtain accurate and reproducible data.

Journal Article↗

Inter-examiner reproducibility of probing pocket depths in molar furcation sites.

This investigation was designed to determine the reproducibility of probing pocket depths in maxillary facial and mandibular facial and lingual grade II and III molar furcation sites. 80 untreated molar teeth with 102 furcation invasions due to periodontitis were probed with a pressure-sensitive periodontal probe by 3 examiners. 8 sites per furcation were measured by each examiner at a single examination. The sequence of examiner probing was rotated in order to evaluate the effect of sequential probing. Tracings were made from radiographs of the inter-root separations in order to classify the interradicular space and to determine the effect of root separation on reproducibility. Data was analyzed by regression analysis. Pearson correlations, intraclass correlations, and the Student-Newman-Keuls test. Analysis indicated a high reproducibility of the maxillary facial and mandibular facial and lingual furcation sites in this untreated adult sample. No effect was due to probing sequence. The mid-root prominences, the line angles, and the internal surface sites of the furcation roots were recordable and reproducible, while the horizontal measurements were not consistently recordable. The reproducibility of the facial and lingual furcation sites that were probed decreased with an increase in probing pocket depth and an increased degree of root separation.

Clinical Competence↗

Label-free protein quantification using LC-coupled ion trap or FT mass spectrometry: Reproducibility, linearity, and application with complex proteomes.

A critical step in protein biomarker discovery is the ability to contrast proteomes, a process referred generally as quantitative proteomics. While stable-isotope labeling (e.g., ICAT, 18O- or 15N-labeling, or AQUA) remains the core technology used in mass spectrometry-based proteomic quantification, increasing efforts have been directed to the label-free approach that relies on direct comparison of peptide peak areas between LC-MS runs. This latter approach is attractive to investigators for its simplicity as well as cost effectiveness. In the present study, the reproducibility and linearity of using a label-free approach to highly complex proteomes were evaluated. Various amounts of proteins from different proteomes were subjected to repeated LC-MS analyses using an ion trap or Fourier transform mass spectrometer. Highly reproducible data were obtained between replicated runs, as evidenced by nearly ideal Pearson's correlation coefficients (for ion's peak areas or retention time) and average peak area ratios. In general, more than 50% and nearly 90% of the peptide ion ratios deviated less than 10% and 20%, respectively, from the average in duplicate runs. In addition, the multiplicity ratios of the amounts of proteins used correlated nicely with the observed averaged ratios of peak areas calculated from detected peptides. Furthermore, the removal of abundant proteins from the samples led to an improvement in reproducibility and linearity. A computer program has been written to automate the processing of data sets from experiments with groups of multiple samples for statistical analysis. Algorithms for outlier-resistant mean estimation and for adjusting statistical significance threshold in multiplicity of testing were incorporated to minimize the rate of false positives. The program was applied to quantify changes in proteomes of parental and p53-deficient HCT-116 human cells and found to yield reproducible results. Overall, this study demonstrates an alternative approach that allows global quantification of differentially expressed proteins in complex proteomes. The utility of this method to biomarker discovery is likely to synergize with future improvements in the detecting sensitivity of mass spectrometers.

Amino Acid Sequence↗

A format for integrating the interpretation of exercise ejection fraction and wall motion and its application in identifying equivocal responses.

The conventional interpretation of ejection fraction change with exercise may be limited because it does not consider the rest value, define equivocal responses or integrate wall motion data reproducibly. Thus, a format was developed for combined interpretation of rest and exercise radionuclide ejection fraction and wall motion by reviewing the reported data for the exercise responses of patients without prior myocardial infarction. The ejection fraction data of 202 normal patients and of 259 patients with coronary artery disease were first fitted to beta distributions. The true positive and false positive rates for coronary disease for each combination of rest and exercise ejection fraction were then determined directly from these distributions. A given rest/exercise ejection fraction combination was "normal" if the false positive rate was greater than the true positive rate, or "abnormal" if the true positive rate was greater than the false positive rate, and "equivocal" when the rates were similar (within a 50% confidence interval). This analytic format, which predicted an inverse relation between rest ejection fraction and the change required with exercise, was then validated prospectively in 854 patients without myocardial infarction (557 with and 297 without angiographic coronary artery disease). Using the conventional criterion of an abnormal test result (less than 0.05 absolute rise in ejection fraction with exercise or a wall motion abnormality), sensitivity was 85 +/- 2% and specificity only 42 +/- 3%. The statistical format had a sensitivity of 70 +/- 2% and specificity of 70 +/- 3%, resulting in a twofold increase in information content. This format has at least two advantages over conventional interpretation: 1) it provides an explicit definition of equivocal responses; and 2) it reproducibly integrates discordant ejection fraction and wall motion responses and allows for the combined analysis of other nonscintigraphic observations, such as age and sex.

Adult↗