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A comparison of the mutagenicity of mainstream cigarette smoke condensates from a representative sample of the U.S. cigarette market with a Kentucky reference cigarette (K1R4F).

The Salmonella mutagenicity assay has been used to investigate the mutagenicity of cigarette smoke and cigarette smoke condensate. The Kentucky reference (K1R4F) cigarette is designed to be representative of full-flavor, low-tar cigarettes sold in the U.S. and to serve as a reference standard for comparative studies on the chemistry and biological activities of cigarette smoke and condensate. The objective of this study was to determine if the mutagenicity of mainstream smoke condensate from the K1R4F, as measured by the Salmonella mutagenicity assay, is representative of the mutagenic activity of U.S. cigarettes. Mainstream smoke condensates prepared in dimethyl sulfoxide from the K1R4F and 73 brand styles (representing greater than 70% of the total U.S. cigarette market) were assayed using Salmonella typhimurium TA98 and TA100 (+S9) at concentrations of 0, 25, 50, 75, 100, 125 and 250 micrograms/plate. Revertants/mg condensate were determined by calculating the slopes of the dose-response curves using linear and nonlinear regression models. Revertants/cigarette were determined by multiplying the revertants/mg condensate by the mg condensate/cigarette. No significant differences (p > 0.05) were observed between the mean mutagenicity of U.S. market and K1R4F mainstream smoke condensates in terms of revertants/mg condensate or revertants/cigarette. Increased variability in mutagenicity was observed among the U.S. brands versus that of the K1R4F. This is not surprising since variability among the U.S. brands would be expected to have both measurement error and brand style variability while the K1R4F variability contains only the measurement error portion. These results demonstrate that the K1R4F is a representative model for the U.S. cigarette market in comparative Salmonella mutagenicity studies using mainstream smoke condensates.

Mutagenicity Tests↗

Measurement variability in DNA flow cytometry of replicate samples.

A Bladder Cancer Flow Cytometry Network study has been carried out aimed at identification of the sources of inter- and intralaboratory variability. Replicate "cocktail" samples containing a mixture of peripheral blood lymphocytes and an aneuploid cell line and samples of peripheral blood lymphocytes serving as a DNA reference standard were distributed to five network laboratories. The samples were stained for DNA using propidium iodide, with each laboratory using its own staining protocol. Sets of these samples were analyzed by flow cytometry to obtain cellular DNA distributions. DNA index and hyperdiploid fraction were calculated for each histogram using an automated technique. Results were evaluated by analysis of variance to identify sources of variability. Three important sources of variation were found that affect flow cytometry in general and- the transportability of flow cytometry results to routine clinical use in particular. The significant variation among laboratories that is constant across time most probably represents stable differences in instrumentation, instrument set-up, and laboratory techniques. This variation can be compensated for, if it is known and stable, to develop transportable classification criteria. The second type of variation, termed the interaction component, represents differences among laboratories that are not constant across time. Sources of this variation include inconsistency in sample preparation, staining, and analysis. The elimination of this type of variation is required for meaningful comparison of data within and among laboratories and the creation of interlaboratory data-bases. The third type of variation represents pure measurement variability and affects the sensitivity of the technique.

Cell Line↗

Response of humans to gamma-irradiated reference Escherichia coli endotoxin.

This study assesses the effect of gamma-irradiation of endotoxin given intravenously to healthy human volunteers. The national reference standard endotoxin derived from E. coli was placed in aqueous medium in sterile-sealed ampoules and divided into four groups. One group received endotoxin with no radiation while the other three received endotoxin with gamma-irradiation at doses of 0.18, 0.36, or 1.08 Mrad. These doses of radiation cause characteristic alterations to the endotoxin molecule, primarily to the O-polysaccharide moiety. Each of the four different preparations of endotoxin was given intravenously to four volunteers at a concentration of 4 ng/kg. The responses for clinical symptoms, cortisol, and growth hormone were significantly and progressively reduced by increasing the irradiation to the endotoxin. Most strikingly, no clinical symptoms were noted with the endotoxin exposed to the highest dose of radiation (1.08 Mrad). Fever, vital signs, white blood cell count, and differential exhibited no statistically significant differences among the groups, but the kinetics of change were altered by increasing doses of gamma-irradiation. Irradiated endotoxin was significantly more effective in decreasing the platelet count than untreated endotoxin. The fever index correlated significantly with maximum temperature, change in temperature, white blood cell count index, mature neutrophil count index, and the cortisol index. Thus, there is dissociation of biological activities for endotoxin in humans due to molecular changes primarily in the O-polysaccharide moiety from exposure to gamma-irradiation.

Adult↗

B-type natriuretic peptide and clinical judgment in emergency diagnosis of heart failure: analysis from Breathing Not Properly (BNP) Multinational Study.

BACKGROUND: We sought to determine the degree to which B-type natriuretic peptide (BNP) adds to clinical judgment in the diagnosis of congestive heart failure (CHF). METHODS AND RESULTS: The Breathing Not Properly Multinational Study was a prospective diagnostic test evaluation study conducted in 7 centers. Of 1586 participants who presented with acute dyspnea, 1538 (97%) had clinical certainty of CHF determined by the attending physician in the emergency department. Participants underwent routine care and had BNP measured in a blinded fashion. The reference standard for CHF was adjudicated by 2 independent cardiologists, also blinded to BNP results. The final diagnosis was CHF in 722 (47%) participants. At an 80% cutoff level of certainty of CHF, clinical judgment had a sensitivity of 49% and specificity of 96%. At 100 pg/mL, BNP had a sensitivity of 90% and specificity of 73%. In determining the correct diagnosis (CHF versus no CHF), adding BNP to clinical judgment would have enhanced diagnostic accuracy from 74% to 81%. In those participants with an intermediate (21% to 79%) probability of CHF, BNP at a cutoff of 100 pg/mL correctly classified 74% of the cases. The areas under the receiver operating characteristic curve were 0.86 (95% CI 0.84 to 0.88), 0.90 (95% CI 0.88 to 0.91), and 0.93 (95% CI 0.92 to 0.94) for clinical judgment, for BNP at a cutoff of 100 pg/mL, and for the 2 in combination, respectively (P<0.0001 for all pairwise comparisons). CONCLUSIONS: The evaluation of acute dyspnea would be improved with the addition of BNP testing to clinical judgment in the emergency department.

Adolescent↗

The role of F-18 FDG positron emission tomography in preoperative assessment of the liver in patients being considered for curative resection of hepatic metastases from colorectal cancer.

PURPOSE: The authors' goal was to determine the sensitivity and specificity of F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) for identifying patients with hepatic metastases from colorectal cancer and the accuracy of PET for determining the number and distribution of lesions within the liver. Intraoperative sonography and surgical inspection and palpation were used as the reference standard. METHODS: Twenty-three patients being evaluated for surgical resection of hepatic metastases from colorectal carcinoma underwent FDG PET before operation. Findings of the PET studies were reviewed in a blinded, retrospective manner, with the results compared with the findings of intraoperative sonography and surgical exploration. Lesions of all sizes were considered in the analysis. RESULTS: The FDG-PET results were positive in 21 of the 22 patients ultimately found to have metastatic disease to the liver, and they were negative in the single patient without metastases. Therefore, for identification of patients with hepatic metastatic disease, PET has a sensitivity of 95% and a specificity of 100%. In all, 48 metastatic lesions were identified in these patients, of which 38 (79%) were identified on PET images. The probability of lesion detection by PET was directly correlated with lesion size (P < 0.01). The assessment of lobar disease distribution in the liver was discordant between PET and surgery in 3 of 23 (13%) patients. CONCLUSIONS: In patients being evaluated for potential curative resection of hepatic metastases from colorectal cancer, FDG PET is accurate for the identification of the presence or absence of metastatic disease to the liver. However, detection of individual lesions depends on their size, and determination of lesion number and distribution within the liver is more accurately accomplished with intraoperative sonography.

Adult↗

Identification of core aldehydes among in vitro peroxidation products of cholesteryl esters.

Synthetic cholesteryl 5-oxovalerate and 9-oxononanoate were used as reference standards for the isolation and identification of cholesteryl ester core aldehydes from tert-butyl hydroperoxide/Fe++ oxidation of synthetic and natural cholesteryl esters. The core aldehydes were recovered from the peroxidation products by thin-layer chromatography as the free aldehydes or the 2,4-dinitrophenylhydrazones and were identified, respectively, by gas-liquid chromatography (GLC) and by GLC combined with mass spectrometry (GC/MS) or by reverse-phase high-performance liquid chromatography (HPLC) and by HPLC with MS (LC/MS). The core aldehydes produced by peroxidation of cholesteryl linoleate were identified as mainly 9-oxononanoates of cholesterol and oxycholesterols, with smaller amounts of the 8-oxooctenoates, 10-oxodecenoates, 11-oxoundecenoates and 12-oxododecenoates. Peroxidation of cholesteryl arachidonate yielded 5-oxovalerates of cholesterol and the oxycholesterols as the main products with smaller amounts of the 4-oxobutyrates, 6-oxohexenoates, 7-oxoheptenoates, 8-oxooctenoates, 9-oxononenoates, 9-oxononadienoates and 10-oxodecadienotes. The oxycholesterols resulting from the peroxidation of the steroid ring were identified as mainly 7-keto-, 7 alpha-hydroxy- and 7 beta-hydroxy-cholesterols and 5 alpha,6 alpha- and 5 beta,6 beta-epoxy-cholestanols. Cholesteryl palmitate and oleate did not yield core aldehydes in the present peroxidation system. In these esters, the sterol and linoleic acid moieties appeared to be oxygenated at about the same rate, while the arachidonic acid moiety reacted more rapidly than did the sterol moiety.

Aldehydes↗

Accuracy of death certificates for coding coronary heart disease as the cause of death.

BACKGROUND: Death certificates are widely used in epidemiologic and clinical investigations and for national statistics. OBJECTIVE: To examine the accuracy of death certificates for coding coronary heart disease as the underlying cause of death. DESIGN: Community-based inception cohort followed since 1948. SETTING: Framingham, Massachusetts. PATIENTS: 2683 deceased Framingham Heart Study participants. MEASUREMENTS: Sensitivity, specificity, and predictive values of the death certificate. The reference standard was cause of death adjudicated by a panel of three physicians. RESULTS: Among 2683 decedents, the death certificate coded coronary heart disease as the underlying cause of death for 942; the physician panel assigned coronary heart disease for 758. The death certificate had a sensitivity of 83.8% (95% CI, 81.1 % to 86.4%), positive predictive value of 67.4% (CI, 64.4% to 70.4%), specificity of 84.1% (CI, 82.4% to 85.7%), and negative predictive value of 92.9% (CI, 91.7% to 94.1%) for coronary heart disease. The death certificate assigned coronary heart disease in 51.2% of 242 deaths (9.0% of total deaths) for which the physician panel could not determine a cause. Compared with the physician panel, the death certificate attributed 24.3% more deaths to coronary heart disease overall and more than twice as many deaths to coronary heart disease in decedents who were at least 85 years of age. When deaths that were assigned unknown cause by the physician panel were excluded, the death certificate still assigned more deaths to coronary heart disease (7.9% overall and 43.1% in the oldest age group). CONCLUSIONS: Coronary heart disease may be overrepresented as a cause of death on death certificates. National mortality statistics, which are based on death certificate data, may overestimate the frequency of coronary heart disease by 7.9% to 24.3% overall and by as much as two-fold in older persons.

Adult↗

Meta-analysis: test performance of ultrasonography for giant-cell arteritis.

BACKGROUND: Giant-cell arteritis is a diagnostic challenge. PURPOSE: To determine the diagnostic performance of ultrasonography for giant-cell arteritis. DATA SOURCES: Studies published up to April 2004 in the MEDLINE, EMBASE, and Cochrane databases; reference lists; and direct contact with investigators. STUDY SELECTION: Studies in any language that examined temporal artery ultrasonography for diagnosis of giant-cell arteritis, enrolled at least 5 patients, and used biopsy or the American College of Rheumatology (ACR) criteria as the reference standard. DATA EXTRACTION: Two reviewers independently graded methodologic quality and abstracted data on sensitivity and specificity of ultrasonography for giant-cell arteritis. Diagnostic performance was determined for the halo sign, stenosis, or occlusion and for any of these ultrasonographic abnormalities. DATA SYNTHESIS: Weighted sensitivity and specificity estimates and summary receiver-operating characteristic (ROC) curve analysis were used. Twenty-three studies, involving a total of 2036 patients, met the inclusion criteria. The weighted sensitivity and specificity of the halo sign were 69% (95% CI, 57% to 79%) and 82% (CI, 75% to 87%), respectively, compared with biopsy and 55% (CI, 36% to 73%) and 94% (CI, 82% to 98%), respectively, compared with ACR criteria. Stenosis or occlusion was an almost equally sensitive marker compared with either biopsy (sensitivity, 68% [CI, 49% to 82%]) or ACR criteria (sensitivity, 66% [CI, 32% to 89%]). Consideration of any vessel abnormality nonsignificantly improved diagnostic performance compared with ACR criteria. Between-study heterogeneity was significant, but summary ROC curves were consistent with weighted estimates. When the pretest probability of giant-cell arteritis is 10%, negative results on ultrasonography practically exclude the disease (post-test probability, 2% to 5% for various analyses). LIMITATIONS: The primary studies were small and of modest quality and had considerable heterogeneity. CONCLUSION: Ultrasonography may be helpful in diagnosing giant-cell arteritis, but cautious interpretation of the test results based on clinical presentation and pretest probability of the disease is imperative.

Adult↗

Rapid identification of serotypes of Mycobacterium avium-M. intracellulare complex by using infected swine sera and reference antigenic glycolipids.

The species of 136 strains of acid-fast bacteria isolated from swine with mycobacteriosis were identified by numerical taxonomy and chemotaxonomy on the basis of mycolic acid subclass composition as members of the Mycobacterium avium-M. intracellulare (MAI) complex. The isolates were further classified by using both thin-layer chromatography of the antigenic glycopeptidolipids (GPL) obtained from the bacteria by the method of Tsang et al. (A. Y. Tsang, I. Drupa, M. Goldberg, J. K. McClatchy, and P. J. Brennan, Int. J. Syst. Bacteriol. 33:285-292, 1983) and the seroagglutination test devised by W. B. Schaefer (Am. Rev. Respir. Dis. 92[Suppl.]:85-93, 1965). For the reference standard, purified antigenic GPL of serotypes 4, 8, and 9 were isolated and their structures were analyzed by negative fast-atom bombardment-mass spectrometry. The fast-atom bombardment-mass spectrometric spectra of the intact GPL antigens of serotypes 4, 8, and 9 agreed with the structures reported earlier by Brennan et al. (P. J. Brennan and M. B. Goren, J. Biol. Chem. 254:4205-4211, 1979; P. J. Brennan, G. O. Aspinall, and J. E. Nam Shin, J. Biol. Chem. 256:6817-6822, 1981). With these antigenic GPL, the thin-layer chromatographic behaviors of the alkali-stable lipids of the above-described isolates were examined. These MAI complex isolates fell into the serotype 8 (85 strains), 4 (33 strains), and 9 (7 strains) and untypeable (11 strains) categories. Furthermore, an enzyme-linked immunosorbent assay (ELISA) based on type-specific glycolipid antigens and infected swine sera was used to diagnose the serological types of the MAI complex isolates. Of 14 cases typed by both the seroagglutination reaction and thin-layer chromatography, 13 showed clear agreement with the ELISA results. The results demonstrated that ELISA using infected sera was especially useful, and it can be recommended on the basis of simplicity, sensitivity, and specificity as an adjunct to the seroaggulutination test and thin-layer chromatography for identification of mycobacteria belonging to the MAI complex.

Agglutination Tests↗

Color Doppler regurgitant jet area for evaluating eccentric mitral regurgitation: an animal study with quantified mitral regurgitation.

OBJECTIVES: The purpose of the present study was to rigorously evaluate the accuracy of the color Doppler jet area planimetry method for quantifying chronic mitral regurgitation. BACKGROUND: Although the color Doppler jet area has been widely used clinically for evaluating the severity of mitral regurgitation, there have been no studies comparing the color jet area with a strictly quantifiable reference standard for determining regurgitant volume. METHODS: In six sheep with surgically produced chronic mitral regurgitation, 24 hemodynamically different states were obtained. Maximal color Doppler jet area for each state was obtained with a Vingmed 750. Image data were directly transferred in digital format to a microcomputer. Mitral regurgitation was quantified by the peak and mean regurgitant flow rates, regurgitant stroke volumes and regurgitant fractions determined using mitral and aortic electromagnetic flow probes. RESULTS: Mean regurgitant volumes varied from 0.19 to 2.4 liters/min (mean [+/- SD] 1.2 +/- 0.59), regurgitant stroke volumes from 1.8 to 29 ml/beat (mean 11 +/- 6.2), peak regurgitant volumes from 1.0 to 8.1 liters/min (mean 3.5 +/- 2.1) and regurgitant fractions from 8.0% to 54% (mean 29 +/- 12%). Twenty-two of 24 jets were eccentric. Simple linear regression analysis between maximal color jet areas and peak and mean regurgitant flow rates, regurgitant stroke volumes and regurgitant fractions showed correlation, with r = 0.68 (SEE 0.64 cm2), r = 0.63 (SEE 0.67 cm2), r = 0.63 (SEE 0.67 cm2) and r = 0.58 (SEE 0.71 cm2), respectively. Univariate regression comparing regurgitant jet area with cardiac output, stroke volume, systolic left ventricular pressure, pressure gradient, left ventricular/left atrial pressure gradient, left atrial mean pressure, left atrial v wave pressure, systemic vascular resistance and maximal jet velocity showed poor correlation (0.08 < r < 0.53, SEE > 0.76 cm2). CONCLUSIONS: This study demonstrates that color Doppler jet area has limited use for evaluating the severity of mitral regurgitation with eccentric jets.

Animals↗

CT colonography: influence of 3D viewing and polyp candidate features on interpretation with computer-aided detection.

PURPOSE: To retrospectively determine if three-dimensional (3D) viewing improves radiologists' accuracy in classifying true-positive (TP) and false-positive (FP) polyp candidates identified with computer-aided detection (CAD) and to determine candidate polyp features that are associated with classification accuracy, with known polyps serving as the reference standard. MATERIALS AND METHODS: Institutional review board approval and informed consent were obtained; this study was HIPAA compliant. Forty-seven computed tomographic (CT) colonography data sets were obtained in 26 men and 10 women (age range, 42-76 years). Four radiologists classified 705 polyp candidates (53 TP candidates, 652 FP candidates) identified with CAD; initially, only two-dimensional images were used, but these were later supplemented with 3D rendering. Another radiologist unblinded to colonoscopy findings characterized the features of each candidate, assessed colon distention and preparation, and defined the true nature of FP candidates. Receiver operating characteristic curves were used to compare readers' performance, and repeated-measures analysis of variance was used to test features that affect interpretation. RESULTS: Use of 3D viewing improved classification accuracy for three readers and increased the area under the receiver operating characteristic curve to 0.96-0.97 (P<.001). For TP candidates, maximum polyp width (P=.038), polyp height (P=.019), and preparation (P=.004) significantly affected accuracy. For FP candidates, colonic segment (P=.007), attenuation (P<.001), surface smoothness (P<.001), distention (P=.034), preparation (P<.001), and true nature of candidate lesions (P<.001) significantly affected accuracy. CONCLUSION: Use of 3D viewing increases reader accuracy in the classification of polyp candidates identified with CAD. Polyp size and examination quality are significantly associated with accuracy.

Adult↗

Comparison of fingerstick hemoglobin A1c levels assayed by DCA 2000 with the DCCT/EDIC central laboratory assay: results of a Diabetes Research in Children Network (DirecNet) Study.

BACKGROUND: The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) high-performance liquid chromatography (HPLC) method for measuring hemoglobin A1c (HbA1c) serves as a reference standard against which other assays are compared. The DCA 2000 + Analyzer (Bayer Inc., Tarrytown, NY, USA), which uses an immunoassay, is a very popular device for measuring HbA1c levels in pediatric diabetes practices. OBJECTIVE: To determine how HbA1c values measured with the DCA 2000 in a multisite, pediatric diabetes clinic setting compare with corresponding HbA1c values measured in the DCCT/EDIC laboratory. DESIGN/METHODS: To examine this question, the Diabetes Research in Children Network (DirecNet) used the DCA 2000 in five clinical centers to measure baseline HbA1c levels in 200 youth with type 1 diabetes mellitus (T1DM) (aged 12.5 +/- 2.8 yr) who were participating in an outpatient clinical trial. At the same visit, an additional blood sample was obtained, refrigerated, and shipped to the DCCT/EDIC central laboratory for determination of HbA1c values. RESULTS: The central laboratory HbA1c value averaged 8.0 +/- 0.9% (mean +/- SD), with a median (25th and 75th quartiles) of 7.8% (7.3 and 8.5%, respectively). The DCA 2000 HbA1c values were strongly correlated (r = 0.94, p < 0.001), but significantly higher than DCCT/EDIC central laboratory values with a mean difference of +0.2% (95% confidence interval +0.14 to 0.23%, p < 0.001). There was some variation in the differences between DCA 2000 and central laboratory values at the five clinical centers (p < 0.001) with mean differences ranging between 0.0 and 0.3%, but differences between the two methods did not vary significantly by age or gender. CONCLUSION: Measurements of HbA1c by the DCA 2000 compare favorably with the DCCT/EDIC central laboratory method, albeit with slightly higher values.

Adolescent↗

Soft-tissue lipomas: accuracy of sonography in diagnosis with pathologic correlation.

PURPOSE: To retrospectively determine the accuracy of sonography in helping to distinguish soft-tissue lipomas from other soft-tissue masses by using histologic proof as the reference standard. MATERIALS AND METHODS: Institutional review board approval was obtained, and informed consent was waived. Thirty-nine patients who underwent sonographic evaluation of a soft-tissue mass followed by biopsy or resection were retrospectively evaluated. Two musculoskeletal radiologists (readers 1 and 2) reviewed the sonographic images, characterized the masses, and rated the level of confidence in the diagnosis of lipoma by using a five-point scale. A level of confidence was also rated for the prospective sonographic report, which was reviewed and designated as reader 3. Receiver operating characteristic (ROC) curves, including 95% confidence intervals, were generated, and the area under the ROC curve (A(z)) was calculated for each reader. Sensitivity, specificity, and accuracy for each reader were calculated by using a confidence rating of 4 or 5 as positive for lipoma. Weighted kappa analysis was also performed to assess for interobserver variability. RESULTS: Histologic examination yielded 25 lipomas and 14 nonlipomas. The echogenicity of lipomas ranged from hypoechoic to hyperechoic relative to muscle, although most were isoechoic or hyperechoic. A(z) values were 0.79 for reader 1, 0.56 for reader 2, and 0.77 for reader 3. There was no significant difference between the A(z) for each reader and for chance. Interobserver agreement was fair, with a kappa value of 0.35 among the three readers. Sensitivities were 52%, 40%, and 52%, and accuracies were 64%, 49%, and 64% for readers 1, 2, and 3, respectively. CONCLUSION: Sonography demonstrates low accuracy in the diagnosis of soft-tissue lipomas.

Adipose Tissue↗

Possible small-bowel neoplasms: contrast-enhanced and water-enhanced multidetector CT enteroclysis.

PURPOSE: To prospectively evaluate the sensitivity and specificity of contrast material-enhanced and water-enhanced multidetector computed tomographic (CT) enteroclysis in depicting small-bowel neoplasms in symptomatic patients, with endoscopic, tissue, and follow-up findings as reference standards. MATERIALS AND METHODS: The study protocol was approved by the Human Research Committee of the institution, and all patients gave written informed consent. Two hundred nineteen patients (108 male, 111 female; age range, 17-98 years; mean, 53.1 years) with clinical suspicion of small-bowel neoplasm underwent contrast- and water-enhanced multidetector CT enteroclysis after normal findings of upper and lower gastrointestinal endoscopy. The prospective interpretations of CT enteroclysis results include evaluation of focal bowel wall thickening, small-bowel masses, small-bowel stenosis, mesenteric stranding, enlarged mesenteric lymph nodes, and visceral metastasis. Positive enteroclysis findings were compared with results of pathologic examination after surgical (n = 35) or endoscopic (n = 20) procedures. Negative results were compared with results of surgery (n = 8), enteroscopy (n = 15), capsule endoscopy (n = 14), and clinical follow-up (n = 127). Sensitivity, specificity, accuracy, and positive and negative predictive values were calculated on a per-patient basis with 95% confidence intervals. RESULTS: Findings of CT enteroclysis were positive in 55 cases and negative in 164. The overall sensitivity and specificity in identifying patients with small-bowel lesions were 84.7% and 96.9%, respectively. The negative and positive predictive values were 94.5% and 90.9%, respectively. Findings of pathologic examination confirmed small-bowel tumor in 50 patients with carcinoid tumor (n = 19), adenocarcinoma (n = 7), lymphoma (n = 5), jejunal adenoma (n = 9), stromal tumor (n = 5), ectopic pancreas (n = 2), angiomatous mass (n = 2), or metastasis (n = 1). Five examinations resulted in false-positive findings. CONCLUSION: Contrast- and water-enhanced multidetector CT enteroclysis had an overall accuracy of 84.7% for depiction of small-bowel neoplasms.

Adolescent↗

A comparison of gross pathology, histopathology, and mycobacterial culture for the diagnosis of tuberculosis in elk (Cervus elaphus).

Using the isolation of Mycobacterium bovis as the reference standard, this study evaluated the sensitivity, specificity and kappa statistic of gross pathology (abattoir postmortem inspection), histopathology, and parallel or series combinations of the two for the diagnosis of tuberculosis in 430 elk and red deer. Two histopathology interpretations were evaluated: histopathology I, where the presence of lesions compatible with tuberculosis was considered positive, and histopathology II, where lesions compatible with tuberculosis or a select group of additional possible diagnoses were considered positive. In the 73 animals from which M. bovis was isolated, gross lesions of tuberculosis were most often in the lung (48), the retropharyngeal lymph nodes (36), the mesenteric lymph node (35), and the mediastinal lymph nodes (16). Other mycobacterial isolates included: 11 M. paratuberculosis, 11 M. avium, and 28 rapidly growing species or M. terrae complex. The sensitivity estimates of gross pathology and histopathology I were 93% (95% confidence limits [CL] 84.97%) and 88% [CL 77.94%], respectively, and the specificity of both was 89% [CL 85.92%]). The sensitivity and specificity of histopathology II were 89% (CL 79.95%) and 77% (CL 72.81%), respectively. The highest sensitivity estimates (93-95% [CL 84.98%]) were obtained by interpreting gross pathology and histopathology in parallel (where an animal had to be positive on at least one of the two, to be classified as combination positive). The highest specificity estimates (94-95% [CL 91-97%] were generated when the two tests were interpreted in series (an animal had to be positive on both tests to be classified as combination positive). The presence of gross or microscopic lesions showed moderate to good agreement with the isolation of M. bovis (Kappa = 65-69%). The results showed that post-mortem inspection, histopathology and culture do not necessarily recognize the same infected animals and that the spectra of animals identified by the tests overlaps.

Abattoirs↗

Immediate 201Tl reinjection: an alternative approach in myocardial perfusion scintigraphy? A comparison with contrast angiographic findings.

Thallium-201 (201Tl) stress-redistribution/reinjection imaging provides a reliable diagnostic approach in patients evaluated for myocardial ischaemia. Immediate reinjection of 201Tl after completing the stress images followed by imaging 1 h later shortens the investigation time to 2.5 h and may provide a novel approach. In this study, we validated the immediate reinjection approach in the assessment of myocardial perfusion and viability using contrast angiographic findings as the reference standard. We studied 114 patients with documented cardiac catheterization data using quantitative planar 201Tl stress/immediate reinjection imaging. The 201Tl findings were compared with contrast angiographic data, coronary arteriographic findings and electrocardiographic data. Myocardial regions were considered to be viable if they (1) showed normal or hypokinetic wall motion, (2) were supplied by patent coronary arteries or by occluded arteries with adequate collateral circulation, or (3) were not related to electrocardiographic infarct site. Myocardial regions were considered to be non-viable if they (1) showed akinetic or dyskinetic wall motion, (2) were supplied by occluded vessels with inadequate collateral circulation, or (3) were related to electrocardiographic infarct site. Of 280 regions with normal or hypokinetic wall motion, 47 (17%) regions showed persistent 201Tl defects compared with 21 of 26 (81%) regions with akinetic/dyskinetic wall motion (P < 0.0001). Of 318 regions supplied by patent vessels, 65 (20%) regions showed persistent 201Tl defects compared with 14 of 22 (64%) regions subtended by occluded vessels (P < 0.0001). When the 201Tl findings were compared with electrocardiographic infarct site, 37 of 259 (14%) remote regions showed persistent defects compared with 42 of 83 (51%) infarct-related regions (P < 0.0001). We conclude that persistent defects on 201Tl immediate reinjection images are significantly more often associated with severe left ventricular wall motion abnormalities, coronary artery occlusion and infarct-related regions. In particular, agreement between the wall motion approach and scintigraphic findings was excellent, with 21 of 26 akinetic or dyskinetic segments showing persistent defects and 233 of 280 normal or hypokinetic segments measured as viable by the reinjection technique, resulting in a sensitivity of 81%, a specificity of 83% and an overall accuracy of 83%. These findings show the potential of immediate 201Tl reinjection imaging for assessing myocardial perfusion and viability.

Adult↗

A study to examine the accuracy of potassium measurements in clinical laboratories across Canada.

OBJECTIVE: To assess the accuracy of potassium measurements in clinical laboratories across Canada. DESIGN AND METHOD: The flame atomic emission spectrophotometry reference method for the determination of potassium was established at the Canadian Reference Laboratory by using National Institute of Science and Technology standard reference materials. The method was subsequently used to assign target values for potassium to Canadian Reference Laboratory's External Quality Assessment human-serum-based testing material. A total of 503 laboratories participated and 9,279 individual External Quality Assessment test results were included in the study. Bias was determined by using difference plots. RESULTS: Clinically significant bias (>1.6%) was observed in 45.9% of the laboratories. Bias ranged from 0.34 mmol/L to -0.54 mmol/L. At low concentrations (<3.5 mmol/L) a positive bias was most frequently observed (14.7% of analytical systems). At high potassium concentrations (>5.1 mmol/L) a negative bias was most frequently observed (31.4% of analytical systems). CONCLUSION: Inaccuracy in potassium results can contribute to test redundancy and mismanagement of patients, while prohibiting the merger of laboratory data from disparate testing sites for the purpose of trending and consolidation within a "universal health record." Inaccurate test results and the lack of standardization among laboratories adversely impact our ability to establish common reference intervals and critical limits. This inability has an adverse effect on medical decisions and patient care.

Bias↗

Meta-analysis: accuracy of quantitative ultrasound for identifying patients with osteoporosis.

BACKGROUND: There is increased interest in quantitative ultrasound for osteoporosis screening because it predicts fracture risk, is portable, and is relatively inexpensive. However, there is no consensus regarding its accuracy for identifying patients with osteoporosis. PURPOSE: To determine the sensitivity and specificity of calcaneal quantitative ultrasound for identifying patients who meet the World Health Organization's diagnostic criteria for osteoporosis. Dual-energy x-ray absorptiometry (DXA) was used as the reference standard. DATA SOURCES: MEDLINE (1966 to October 2005), EMBASE (1993 to May 2004), Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews (1952 to March 2004), and the Science Citation Index (1945 to April 2004). STUDY SELECTION: English-language articles that evaluated the sensitivity and specificity of calcaneal quantitative ultrasound for identifying adults with DXA T-scores of -2.5 or less at the hip or spine. DATA EXTRACTION: Two authors independently reviewed articles and abstracted data. DATA SYNTHESIS: The authors identified 1908 potentially relevant articles, of which 25 met the inclusion criteria, and calculated the sensitivity and specificity of quantitative ultrasound over a range of thresholds. For the quantitative ultrasound index parameter T-score cutoff threshold of -1, sensitivity was 79% (95% CI, 69% to 86%) and specificity was 58% (CI, 44% to 70%) for identifying individuals with DXA T-scores of -2.5 or less at the hip or spine. For a T-score threshold of 0, sensitivity improved to 93% (CI, 87% to 97%) but specificity decreased to 24% (CI, 10% to 47%). At a pretest probability of 22% (for example, a 65-year-old white woman at average risk), the post-test probability of DXA-determined osteoporosis was 34% (CI, 26% to 41%) after a positive result and 10% (CI, 5% to 12%) after a negative result when using a T-score cutoff threshold of -1. Analysis of other quantitative ultrasound parameters (for example, broadband ultrasound attenuation) revealed similar estimates of accuracy. LIMITATIONS: The relatively small number of included studies limited the authors' ability to evaluate the effects of heterogeneous study characteristics on the diagnostic accuracy of quantitative ultrasound. CONCLUSIONS: The currently available literature suggests that results of calcaneal quantitative ultrasound at commonly used cutoff thresholds do not definitively exclude or confirm DXA-determined osteoporosis. Additional research is needed before use of this test can be recommended in evidence-based screening programs for osteoporosis.

Absorptiometry, Photon↗