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Computer-aided diagnosis of dysplasia in Barrett's esophagus using endoscopic optical coherence tomography.

Barrett's esophagus (BE) and associated adenocarcinoma have emerged as a major health care problem over the last two decades. Because of the widespread use of endoscopy, BE is being recognized increasingly in all Western countries. In clinical trials of endoscopic optical coherence tomography (EOCT), we defined certain image features that appear to be characteristic of precancerous (dysplastic) mucosa: decreased scattering and disorganization in the microscopic morphology. The objective of the present work is to develop computer-aided diagnosis (CAD) algorithms that aid the detection of dysplasia in BE. The image dataset used in the present study was derived from a total of 405 EOCT images (13 patients) that were paired with highly correlated histologic sections of corresponding biopsies. Of these, 106 images were included in the study. The CAD algorithm used was based on a standard texture analysis method (center-symmetric auto-correlation). Using histology as the reference standard, this CAD algorithm had a sensitivity of 82%, specificity of 74%, and accuracy of 83%. CAD has the potential to quantify and standardize the diagnosis of dysplasia and allows high throughput image evaluation for EOCT screening applications. With further refinements, CAD could also improve the accuracy of EOCT identification of dysplasia in BE.

Adenocarcinoma↗

Computerized analysis of restriction fragment length polymorphism patterns: comparative evaluation of two commercial software packages.

Two computerized restriction fragment length polymorphism pattern analysis systems, the BioImage system and the GelCompar system (Molecular Analyst Fingerprinting Plus in the United States), were compared. The two systems use different approaches to compare patterns from different gels. In GelCompar, a standard reference pattern in one gel is used to normalize subsequent gels containing lanes with the same reference pattern. In BioImage, the molecular sizes of the fragments are calculated from size standards present in each gel. The molecular size estimates obtained with the two systems for 12 restriction fragments of phage lambda were between 97 and 101% of their actual sizes, with a standard deviation of less than 1% of the average estimated size for most fragments. At the window sizes used for analysis, the GelCompar system performed somewhat better than BioImage in identifying visually identical patterns generated by electrophoretic separation of HhaI-restricted DNA of Listeria monocytogenes. Both systems require the user to make critical decisions in the analysis. It is very important to visually verify that the systems are finding all bands in each lane and that no artifacts are being detected; both systems allow manual editing. It is also important to verify results obtained in the pattern matching or clustering portions of the analysis.

Bacteriophage lambda↗

Comparison of the Vitek gram-positive susceptibility 106 card, the MRSA-Screen latex agglutination test, and mecA analysis for detecting oxacillin resistance in a geographically diverse collection of clinical isolates of coagulase-negative staphylococci.

The Vitek automated susceptibility testing system with a modified gram-positive susceptibility (GPS) 106 card (bioMerieux Vitek, Inc., Hazelwood. Mo.) and a rapid slide latex agglutination test (MRSA-Screen test; Denka Seiken Co., Ltd., Tokyo, Japan) were evaluated for their abilities to detect oxacillin resistance in coagulase-negative staphylococci (CoNS). The reference broth microdilution method and the detection of the mecA gene by PCR ("gold standard" reference result) were used to compare the results obtained with the commercial products. A total of 123 clinical isolates consisting of eight species were selected from U.S. surveillance collections. Among the mecA-positive isolates (95 strains), 30 isolates were initially negative on the MRSA-Screen test read at 3 min. When the agglutination reaction was extended for 10 min, 26 of the 30 isolates became positive. For a different four isolates, the oxacillin MIC was < or =0.25 microg/ml on the Vitek GPS 106 card. Among the mecA-negative isolates (28 strains), for two Staphylococcus warneri, two S. lugdunensis, and two S. saprophyticus strains MICs were > or =0.5 microg/ml by the reference broth microdilution method. Four of these isolates were also categorized as resistant with the Vitek GPS 106 card and two isolates were positive by the MRSA-Screen test. Overall, the MRSA-Screen test, GPS 106 card, and reference broth microdilution method had sensitivities of 95.7 (result at 10 min), 95.7, and 100%, respectively, and specificities of 92.8, 85.7, and 78.5%, respectively. Although the MRSA-Screen test required a slight procedural modification, both commercial methods achieved a sensitivity and specificity at detecting oxacillin resistance in CoNS at a level that was acceptable for clinical laboratory use.

Bacterial Proteins↗

Evaluation of 12 commercial tests and the complement fixation test for Mycoplasma pneumoniae-specific immunoglobulin G (IgG) and IgM antibodies, with PCR used as the "gold standard".

Serology and nucleic acid amplification are the main diagnostic tools for the diagnosis of Mycoplasma pneumoniae infection. Since no reference standard is generally accepted, serologic assays for M. pneumoniae have not been evaluated on a broad scale. In this study, 12 commercially available serologic assays (for immunoglobulin G [IgG] and IgM) and the complement fixation test (CFT) were evaluated by using M. pneumoniae DNA detection by real-time PCR as the "gold standard." The assays tested were Platelia EIA (Bio-Rad), SeroMP EIA (Savyon), Serion classic EIA (Virion/Serion), Biotest EIA (Biotest), Ridascreen EIA (r-Biopharm), AniLabsystems EIA (Labsystems), Novum EIA (Novum Diagnostica), Diagnosys EIA (MP products), Genzyme/Virotech EIA, ImmunoWell EIA (Genbio), ImmunoCard EIA (Meridian), and SerodiaMycoII microparticle agglutination (Fujirebio). Serum samples (n = 46) from 27 PCR-positive patients with a known first day of disease and sera (n = 33) from PCR-negative controls were obtained from prospective studies of acute lower respiratory tract infections. Additionally, control sera (n = 63) from patients with acute viral or bacterial respiratory infections other than those caused by M. pneumoniae were tested. The results showed low specificities for both the Novum and the ImmunoCard IgM assays. The IgM assays with the best performances in terms of sensitivity and specificity were AniLabsystems (77% and 92%, respectively), SeroMP (71% and 88%, respectively), and CFT (65% and 97%, respectively). Good receiver operating characteristic areas under the curve were found for CFT (0.94), the Platelia assay (0.87), and the AniLabsystems assay (0.85). We conclude that there are few commercial serologic assays for the detection of M. pneumoniae infections with appropriate performances in terms of sensitivity and specificity and that PCR has become increasingly important for the diagnosis of M. pneumoniae infections in defined groups of patients.

Antibodies, Bacterial↗

Quality assurance system using ISO 9000 series standards to improve the effectiveness and efficacy of the Headache Centre.

The ISO 9000 series has been adopted as a reference standard and operating system for a Quality Assurance project involving all the units of the Polyclinic of Modena, within which the Headache Centre operates, to guarantee a clearly-defined standard of service to the client and the promotion of continuous quality improvement. The implementation of the quality system, which necessitated analysis and description of the process of headache diagnosis and treatment currently being applied, highlighted those aspects that did not conform with the quality objective, primarily, the long waiting list for admission. Since ready accessibility is a basic requisite for the quality of health care services, a new organisational set-up was introduced, and is still in place, with the aim of enabling patients who are really in need to be admitted to the Headache Centre without undue delay.

Headache↗

Double-antibody radioimmunoassay of serum insulin: effect of use of hormone-depleted human serum.

Human serum can be depleted of insulin and growth hormone by treatment with dextran-coated charcoal or by dialysis, or both. Inclusion of such hormone-depleted serum in the standard curve of a double-antibody radioimmunoassay for immunoreactive insulin more nearly mimics the conditions under which an unknown human serum sample is assayed. Compared to the usual standard curve in which serum albumin is the only protein, the addition of hormone-depleted serum can cause an increase (by an average 64% under the conditions we used) in the absolute value for apparent insulin in serum. The effect of hormone-depleted serum should be tested in the standard curves of double-antibody radioimmunoassays and included routinely in these standard curves if it changes the results. When used in conjunction with an eventual reference standard for human insulin, this modification of the insulin assay may make the measured values of human serum insulin from different laboratories more comparable.

Blood↗

Improvements in cancer staging with PET/CT: literature-based evidence as of September 2006.

PET/CT with 18F-FDG is increasingly being used for staging, restaging, and treatment monitoring for cancer patients. CT is still frequently used only for attenuation correction and lesion localization. However, increasing sales of high-end scanners that combine PET with 64-detector CT strongly suggest that the field is moving toward a comprehensive concept, whereby diagnostic CT studies during intravenous contrast material application are combined with the highest-quality PET studies. At many institutions, in-line PET/CT has replaced separately acquired PET and CT examinations for many oncologic indications. This replacement has occurred despite the fact that only a relatively small number of well-designed prospective studies have verified imaging findings against the gold standard of histopathologic tissue evaluation. However, a large number of studies have used acceptable reference standards, such as pathology, imaging, and other clinical follow-up findings, for validating PET/CT findings. From these data, we believe, has emerged reliable evidence in support of the notion that PET/CT offers diagnostic advantages over its individual components for the major cancers.

Clinical Trials as Topic↗

A comparison of Australian and Canadian calibration coefficients for air kerma and absorbed dose to water for 60Co gamma radiation.

Australian and Canadian calibration coefficients for air kerma and absorbed dose to water for 60Co gamma radiation have been compared using transfer standard ionization chambers of types NE 2561 and NE 2611A. Whilst the primary standards of air kerma are similar, both being thick-walled graphite cavity chambers but employing different methods to evaluate the Awall correction, the primary standards of absorbed dose to water are quite different. The Australian standard is based on measurements made with a graphite calorimeter, whereas the Canadian standard uses a sealed water calorimeter. The comparison result, expressed as a ratio of calibration coefficients R=N(ARPANSA)/N(NRC), is 1.0006 with a combined standard uncertainty of 0.35% for the air kerma standards and 1.0052 with a combined standard uncertainty of 0.47% for the absorbed dose to water standards. This demonstrates the agreement of the Australian and Canadian radiation dosimetry standards. The results are also consistent with independent comparisons of each laboratory with the BIPM reference standards. A 'trilateral' analysis confirms the present determination of the relationship between the standards, within the 0.09% random component of the combined standard uncertainty for the three comparisons.

Absorption↗

Certification of the methylmercury content in SRM 2977 mussel tissue (organic contaminants and trace elements) and SRM 1566b oyster tissue.

The methylmercury content in two new marine bivalve mollusk tissue Standard Reference Materials (SRMs) has been certified using results of analyses from the National Institute of Standards and Technology (NIST) and two other laboratories. The certified concentrations of methylmercury were established based on the results from four and six different (independent) analytical methods, respectively, for SRM 1566b Oyster Tissue (13.2 +/- 0.7 microg/kg) and SRM 2977 Mussel Tissue (organic contaminants and trace elements) (36.2 +/- 1.7 microg/kg). The certified concentration of methylmercury in SRM 1566b is among the lowest in any certified reference material (CRM).

Animals↗

A coulometric method for determining substances that interfere with the measurement of water in oils and other chemicals by the Karl Fischer method.

In order to fulfill a need to measure water in crude oils containing materials that interfere with the measurement of water by the Karl Fischer method, by reacting with iodine or iodide, a coulometric method has been developed and validated using 0.1 mol L(-1) Sodium thiosulfate as a calibrant. These interfering substances were measured in water-mass-equivalents, which were expressed as the mass of water that reacts with an equal mass of iodine in the Karl Fischer method. The SO(2)-free reagent that has been modified reacts quantitatively with sodium thiosulfate, cysteine and ascorbic acid but does not react with vinyl acetate. The level of interfering substances was measured in five transformer oils (including Reference Materials RM 8506 and RM 8507), a high and a low sulfur crude oil (Standard Reference Materials SRM 2721 and SRM 2722 respectively), a white oil, a high-vacuum oil and a high-viscosity base-stock oil. One oil contained less than 10 mg kg(-1) (water-mass-equivalents of interfering substances in oil) and two oils (RM 8507 and Drakeol 35) contained no measurable amount of interfering material (<0.2 mg kg(-1)). SRM 2271, a sour crude oil contained 834 mg kg(-1) (standard deviation (SD)=25 mg kg(-1)) (water-mass-equivalents of interfering substances in oil). Approximately 20% of this material was volatile and an additional 20% appeared to undergo some degradation (possibly oxidation) once the oil was exposed to air. These results indicate that this is a general method for measuring substances in oils that react with iodine and that it is capable of measuring in a variety of oils, using commercial instrumentation, interfering substances that inflate water measurements.

Journal Article↗

[Ca 125 in the diagnosis and follow-up of ovarian neoplasia].

In 31 patients affected by epithelial ovary carcinomas we considered the connection between the levels of Ca 125 and the clinical evolution of disease, and examined the predicted value of Ca 125 for tumoral progression. Ca 125 was calculated at least twice, from one to seven days before the operation and, later on, every two months for an accurate follow-up. The samples of plasma (with EDTA) frozen at -20 degrees C, until the dosage moment, were collected for the analytical determination of Ca 125. The determination was carried out by IRMA technique, at sandwich, using a reference standard with arbitrary units (U/ml). In 23 of the 31 patients the levels of Ca 125 were higher than the reference value. No correlation was evident between positiveness of Ca 125 and histologic standard, whereas antigenic positiveness was higher when the stages were more advanced. With regard to the same stages, the incidence of levels greater than 35 U/ml, in the case Ic (100%), was higher (p less than 0.05), compared to the ones Ia and Ib (14.3%). Sensitivity, specificity, predicted positive value and diagnostic accuracy showed a positive correlation between clinical study and the levels of Ca 125. Only one woman, belonging to a group of relapsed patients revealed the levels of Ca 125 less than 35 U/ml. Considering a minimum increase of 50% in the levels of Ca 125, a significant prognosis in patients before the relapse diagnosis could be made by clinical or paraclinical methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Tumor-Associated, Carbohydrate↗

Development of a provisional reference human cord serum standard for alpha-fetoprotein determination.

A lyophilized human cord serum secondary reference standard (988 vials of 1 mL/vial) has been prepared at the Laboratory Centre for Disease Control (L.C.D.C.) in Ottawa to assist in the standardization of AFP determinations. HBSAG-negative lots of cord serum were used to prepare the standard. The moisture content of the freeze-dried material was less than 0.5 percent. AFP mass calibration standards were prepared by direct weighing in duplicate of highly purified freeze-dried material. Two RIA calibration runs were conducted on the reference cord serum employing the WHO First International Standard for AFP (72/225) and L.C.D.C. mass standards. Parallelism of dose response curves within assays was demonstrated between reference cord serum and mass standards and between the latter and the WHO standard. The mean WHO kIU of AFP per vial of reference serum (+/- coefficient of variation) was 63.0 +/- 6.4 and the mean mass of AFP determined as micrograms per vial was 80.7 +/- 7.9. A small-scale (pilot) interlaboratory calibration of the reference cord serum in mass units resulted in heterogeneous AFP estimates which ranged from 54.4 to 80.7 micrograms/vial. Greater uniformity of the latter results was noted following conversion of the mass estimates to WHO international units conversion factors provided by several laboratories.

Fetal Blood↗

Growth patterns of school-children in Bahrain.

The aim of this study is to assess physical growth of school children in Bahrain. Cross-sectional data on 1593 children (818 boys and 775 girls), aged 6.5 to 18.5 years were collected in 1986. Anthropometric measures included height, weight, mid-arm circumference, triceps, biceps, subscapular and suprailiac skinfold thickness. At all ages median (P50) heights and weights of Bahraini boys and girls are below the 50th percentiles of the North American reference standard (NCHS). Median heights of both Bahraini sexes falls between the 25th and 5th percentiles of the reference data. As for weight, the median of boys fluctuates between the 25th and 5th percentiles, while that of girls fluctuates between the 50th and 10th percentiles of the standard. When compared to the American standard, median triceps skinfold of Bahraini boys and girls falls between the 50th and 25th percentiles. The median arm circumference of both sexes is close to the 5th percentiles. In general, the skinfold measurements indicate a high subcutaneous fat store, suggesting a lack of muscle development. Health, genetic and other factors associated with growth patterns of Bahraini children are discussed.

Adipose Tissue↗

The sensitivity and specificity of single-field nonmydriatic monochromatic digital fundus photography with remote image interpretation for diabetic retinopathy screening: a comparison with ophthalmoscopy and standardized mydriatic color photography.

PURPOSE: To evaluate single-field digital monochromatic nonmydriatic fundus photography as an adjunct in the screening of diabetic retinopathy. DESIGN: Prospective, comparative, observational case series. METHODS: Patients with type I and type II diabetes mellitus (n = 197) were sequentially evaluated by three different techniques: single-field digital monochromatic nonmydriatic photography; dilated ophthalmoscopy by an ophthalmologist; and seven Early Treatment Diabetic Retinopathy Study (ETDRS) standardized 35-mm color stereoscopic mydriatic images. The seven stereoscopic color photographs served as the reference standard and were compared with either ophthalmoscopy or a single digital photograph transmitted electronically to a reading site. Levels of agreement were determined by kappa analyses. The sensitivity and specificity of the three methods were compared based on a threshold for referral to further ophthalmologic evaluation (ETDRS level > or =35). RESULTS: There was highly significant agreement (kappa = 0.97, P =.0001) between the degree of retinopathy detected by a single nonmydriatic monochromatic digital photograph and that seen in seven standard 35-mm color stereoscopic mydriatic fields. The sensitivity of digital photography compared with color photography was 78%, with a specificity of 86%. Agreement was poor (kappa = 0.40, P =.0001) between mydriatic ophthalmoscopy and the seven-field standard 35-mm color photographs. Sensitivity of ophthalmoscopy compared with color photography was 34%, with a specificity of 100%. CONCLUSION: A single nonmydriatic monochromatic wide-field digital photograph of the disk and macula was more sensitive for diabetic retinopathy screening than mydriatic ophthalmoscopy, the currently accepted screening method. When adjudicated by standard seven-field color photographs, the higher sensitivity of digital photography primarily reflected the reduced sensitivity of ophthalmoscopy in detecting early retinopathy.

Adult↗

Measurement standards for strontium-89 for use in bone palliation.

Strontium-89 standards have been prepared for use in calibrating instruments in the measurement chain from production in reactors to administration in the clinic or radiopharmacy. Alternate reactor production schemes were evaluated to yield high purity 89Sr with minimum 85Sr impurity. Following purification to remove radionuclidic impurities, samples of 89Sr were standardized by high-efficiency liquid-scintillation counting with a relative expanded uncertainty (intended to approximate two standard deviations) of 0.48%. A Standard Reference Material, SRM 4426A, was prepared and distributed to radiopharmaceutical manufacturers and other customers. The standard sources of 89Sr were used in different geometries to calibrate high purity Ge semiconductor detectors, re-entrant ionization chambers and commercial radionuclide calibrators. The latter included Capintec dose calibrators and the Capintec beta C NaI(Tl) scintillation counter.

Bone Diseases↗

Ultrafast MR imaging in pediatric neuroradiology.

PURPOSE: To compare the diagnostic information obtained from ultrafast MR imaging with standard MR imaging techniques in pediatric neuroradiology. The goal was to judge whether ultrafast methods can be used to replace standard methods and reduce the need for sedation or general anesthesia as a result of the considerably shorter scan times. MATERIAL AND METHODS: Our prospective study involved 125 patients. Routine clinical imaging was performed along with two ultrafast methods. Single shot fast spin echo (SSFSE) was used to give T2-weighted images and an echo planar imaging (EPI) sequence to provide a T1-weighted images. The ultrafast images were presented to an experienced neuroradiologist who was also given the information present on the initial referral card. These reports based on the ultrafast images were then compared with the formal radiologic report made solely on the basis of the standard imaging. RESULTS: The overall sensitivity and specificity for ultrafast imaging when compared to the reference standard were 78% and 98% with positive and negative predictive values of 98% and 76%. Pathologies characterized by small areas of subtle T2 prolongation were difficult or impossible to see on the ultrafast images but otherwise they provided reliable information. CONCLUSIONS: This paper demonstrates that ultrafast MR imaging can diagnose many pediatric intracranial abnormalities as well as standard methods. Anatomic resolution limits its capacity to define subtle developmental anomalies and contrast resolution limitations of the ultrafast methods reduce the detection of pathology characterized by subtle T2 prolongation.

Brain Diseases↗

Analysis of human serum immunoglobulin G against O-acetyl-positive and O-acetyl-negative serogroup W135 meningococcal capsular polysaccharide.

The capsular polysaccharide of Neisseria meningitidis serogroup W135 is expressed in both O-acetyl-positive (OA+) and O-acetyl-negative (OA-) forms. This study investigates the impact of OA status (OA+ versus OA-) on serological measurements of anti-W135 immunoglobulin G (IgG) antibodies in immunized adults. W135-specific serum antibody assignments were made for 28 postimmunization sera from adults by enzyme-linked immunosorbent assay using the meningococcal standard reference serum CDC1992. The established IgG concentration in micrograms per milliliter ([IgG]microg/ml) for CDC1992 against OA+ antigen (16.2 microg/ml) was used as a reference to assign a concentration of 10.13 microg/ml IgG against OA- antigen by cross-standardization. Overall, the IgG assignments for these sera were higher against OA+ antigen (geometric mean concentration [GMC] = 7.16 microg/ml) than against OA- antigen (GMC = 2.84 microg/ml). However, seven sera showed higher specific [IgG]microg/ml values against the OA+ antigen than against the OA- antigen. These sera were also distinguished by the inability of fluid-phase OA- antigen to compete for antibody binding to OA+ solid-phase antigen. Although there was no overall difference in functional activity measured by complement-mediated serum bactericidal assay (SBA) against OA+ and OA- target bacteria (geometric mean titers of 9,642 and 9,045, respectively), three serum specimens showed a large difference in SBA antibody titers against OA+ versus OA- W135 target bacteria, which may reflect different epitope specificities for these sera. Our data indicate that, for some sera, the agreement in anti-OA+ versus anti-OA- W135 IgG assignments is serum specific and does not reflect the functional (killing) activity in vitro.

Acetylation↗

Comparison of protein values in cerebrospinal fluid by nephelometry and radial immunodiffusion.

Various parameters of three radial immunodiffusion systems, a kinetic nephelometer and two laser nephelometers were compared in a measurement of IgG and albumin in cerebrospinal fluid. Greater precision for IgG and albumin determinations was found with two RID systems. Correlation coefficients between methods ranged from 0.71 to 0.94. The generally poor correlations of methods, combined with the results of accuracy studies employing WHO standard reference dilutions and proportional errors demonstrated by linear regression equations, illustrate graphically the need for standardization in the field of immunochemical determinations. Our preliminary studies of the IgG/Alb ratio in cerebrospinal fluid of multiple sclerosis patients agreed with the work of others. In each case, the ratio was elevated or borderline high.

Albumins↗

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