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Multiplexing molecular diagnostics and immunoassays using emerging microarray technologies.

Enzyme-linked immunosorbent assays (ELISA) are frequently used for quantitative measurement of the presence of protein, for single-analyte testing, in a sample. The application of ELISA in a microarray format has the potential to simultaneously measure the presence and/or concentrations of numerous proteins, in multiplex testing, all contained in a small drop of test fluid. Microspot microarray technology, in combination with protein biomarkers and nucleic acid diagnostics, appears to be the future high-performance analytical platform of choice. Validation of a large number of disease markers in both molecular and protein diagnostics has paved the way for the emergence of the multiplex assay. Initially, simple low-throughput multiplex assays were tested using the immunoassay format. These were followed by low-level multiplexing and high-throughput array-based immunoassays. More recently, two types of high-level multiplexing and high-throughput diagnostic methods using microspot arrays and bead arrays have been successfully developed to complement single-analyte assays. The value in rapid diagnostic evaluation for high-throughput multiplex, diagnostic test systems based on sound assay design must take into account data screening, normalization and statistical evaluation of possible concentration measurement, data errors and automated operation. Benefits of using multiplex array platforms include improved-quality patient care, as well as cost effectiveness and time saving. These multiplex methods also set the stage for future protein/nucleic acid codetection. Currently, the one analyte at a time test scheme is still dominant; nonetheless, the multiplex microspot microarray tests evaluated in a single multiassay analyzer are expected to become a significant part of clinical diagnostic testing within the next 5-10 years. This review is focused on microspot array and bead array methods for providing high throughput and a high degree of multiplexing in diagnostic testing.

Humans↗

The scientific literature in diagnostic radiology for American readers: a survey and analysis of journals, papers, and authors.

The scientific literature in diagnostic radiology for American readers was surveyed by studying the recent growth of its journals, papers and authors. The number of journals has increased rapidly, following the growth in the production of papers. Of the 36 scientific diagnostic radiology journals available at a university medical center, 18 began publication in 1973 or later. The proliferation of new journals should moderate as the size of the American diagnostic radiology research community stabilizes and the newer journals publish a growing share of the papers. Citation analysis, a method of studying interrelationships between papers and journals, showed that citations from papers published in clinical journals to papers published in diagnostic radiology journals accounted for 6% of total citations made in those clinical journals. This observation indicates that research in diagnostic radiology has considerable relevance to research in clinical medicine. Although the number of papers from American diagnostic radiology researches increased from 468 papers in two journals in 1960 to 2861 papers in 16 journals in 1984, the number of researchers increased more rapidly, resulting in a decline in aggregate productivity. At the same time, the average number of authors per paper increased from 2.15 in 1960 to 4.36 in 1985. The first authorship of a scientific paper appears to be the most suitable quantitative measure of research productivity. Study of a sample of 130 diagnostic radiology researchers showed that, on average, each researcher published 3.8 papers as first author in the 5 years from 1980 to 1984. The most prolific 15% of the authors published 52% of the papers.

Authorship↗

Diagnostic impact of four postprocessing techniques in evaluating contrast-enhanced three-dimensional MR angiography.

OBJECTIVE: The purpose of this study was to determine the added diagnostic value of various three-dimensional (3D) data viewing techniques when analyzing contrast-enhanced 3D MR angiography. MATERIALS AND METHODS: Twenty patients (mean age, 62 years) with symptomatic peripheral vascular disease were assessed with breath-hold, contrast-enhanced 3D MR angiography and catheter angiography, which served as the standard of reference. After an initial interpretation of the 3D MR angiographic data sets based only on standardized maximum intensity projections (MIP), the diagnostic gain of the stepwise addition of interactive multiplanar reformations, shaded-surface displays (SSD), and virtual intraarterial endoscopy (VIE) images was calculated. Time required for each step of postprocessing was measured. RESULTS: Pathologic changes were revealed by catheter angiography in 60 vascular segments (50 severe stenoses, seven aneurysms, and three occlusions). The average postprocessing times were MIP, 8 min (range, 5-12 min); multiplanar reformations, 9 min (range, 3-11 min); SSD, 15 min (range, 8-25 min); and VIE, 40 min (range, 18-63 min). Addition of multiplanar reformations to MIPs resulted in the greatest gain of diagnostic accuracy, from 92% to 96%, and diagnostic confidence. When analysis was based on all four techniques, receiver operating characteristic curve analysis revealed only minimal improvements in diagnostic confidence, whereas diagnostic accuracy remained unchanged at 96%. CONCLUSION: Accurate and time-effective analysis of contrast-enhanced 3D MR angiography should be based on MIP algorithms and multiplanar reformations. Additional evaluation with VIE or SSD techniques is time-consuming and provides little diagnostic gain.

Adult↗

Diagnostic accuracy of CT-guided automated needle biopsy of lung nodules.

OBJECTIVE: The purpose of this study was to determine the factors influencing diagnostic accuracy in CT-guided automated needle biopsies of lung nodules. SUBJECTS AND METHODS: One hundred thirty-eight consecutive CT-guided automated needle biopsy procedures were performed in 123 patients (124 pulmonary nodules). Factors for diagnostic accuracy were evaluated through analysis of the procedures, which were classified into a success group (true-positive and true-negative) and a failure group (false-positive and false-negative). RESULTS: Final diagnoses were 81 malignant lesions (91 biopsies) and 43 benign lesions (47 biopsies). More than two CT-guided biopsies were performed for 13 lesions. Seventy lesions were true-positive, 44 were true-negative, three were false-positive, and 21 were false-negative. The overall diagnostic accuracy was 82.6%. The sensitivity for malignancy and specificity for benign lesions were 76.9% and 93.6%, respectively. Positive and negative predictive values were 95.9% and 67.7%, respectively. Lesion size was a significant factor contributing to diagnostic accuracy (p = 0.014). Mean diameters of lesions (+/-SD) in the success and failure groups were 24.1+/-12.4 mm and 17.6+/-7.8 mm, respectively. For lesions 6-10 mm in diameter, diagnostic accuracy was 66.7%; for lesions 11-20 mm in diameter, 78.9%; for lesions 21-30 mm in diameter, 86.7%; for lesions 31-50 mm in diameter, 93.3%; and for lesions 51-70 mm in diameter, 100%. CONCLUSION: Lesion size was a determining factor in diagnostic accuracy. Diagnostic accuracy decreased in proportion to the decrease in the lesion diameter.

Adult↗

Comparison of needle core biopsy and fine-needle aspiration for diagnostic accuracy in musculoskeletal lesions.

CONTEXT: Needle core biopsy has been reported to be the choice of biopsy for musculoskeletal tumors. Fine-needle aspiration, on the other hand, has been widely accepted for nonmusculoskeletal tumors, but is only used in selected medical centers for musculoskeletal tumors. While fine-needle aspiration appears to have advantages to needle core biopsy in the aspects of simplicity and cost, the diagnostic accuracy should be the most critical parameter in determining the choice of biopsy. However, few studies comparing the diagnostic accuracy of these 2 biopsy methods have been performed. OBJECTIVE: This study was designed to compare the diagnostic accuracy of fine-needle aspiration and needle core biopsy in musculoskeletal tumors. DESIGN: Prospective study was performed in patients aged 10 years or older. Diagnostic accuracy was compared in 50 consecutive concurrent needle core biopsies and fine-needle aspirations of musculoskeletal lesions. RESULTS: For primary musculoskeletal lesions, fine-needle aspiration achieved a diagnostic accuracy rate of 88% for nature of lesion, 64% for specific diagnosis, 78% for histologic grading, and 74% for histologic typing. Needle core biopsy achieved an accuracy rate of 93% for nature of lesions, 83% for specific diagnosis, 83% for histologic grading, and 90% for histologic typing. Both biopsy methods have a higher diagnostic accuracy rate for high-grade tumors than for low-grade or benign lesions in determining the nature, specific diagnosis, and histologic grading. CONCLUSIONS: The needle core biopsy has a higher diagnostic accuracy than fine-needle aspiration in all aspects, including determining the nature of the tumor, establishing the histologic type and grade, and achieving a specific diagnosis.

Adolescent↗

Structural variant discovery and diagnostic impact in rare diseases from short-read and long-read sequencing.

Rare diseases collectively affect 1 in 10 individuals, yet current genetic testing fails to identify a causal variant for most cases. At present, cytogenetic methods and/or sequencing approaches such as exome (ES) or short-read genome sequencing (srGS) represent the state-of-the-art for comprehensive clinical discovery of sequence and structural variants (SVs), including copy number variants, balanced SVs, complex SVs, and tandem repeats (TRs). Recently, long-read genome sequencing (lrGS), coupled with multiomics data, has presented great promise to resolve variation in genomic regions recalcitrant to characterization by srGS such as highly repetitive simple repeat sequences and segmental duplications. However, there are few guidelines to enable clinical interpretation of genetic variation in these highly repetitive genomic regions, and the enthusiasm of the field in adopting lrGS has made it difficult to assess the true added diagnostic yield of this technology due to widely variable and inconsistently applied analytic pipelines and variable degrees of pre-screening by ES or srGS. Here, we investigated the contribution of SVs to rare diseases using srGS as a front-line strategy when paired with highly sensitive SV discovery and evaluate the added diagnostic yield of incorporating lrGS for a subset of cases. Our srGS analysis encompassed 1,462 families (3,450 individuals) recruited through the Broad Institute Center for Mendelian Genetics and the Genomics Research to Elucidate the Genetics of Rare Diseases (GREGoR) programs. Diagnostic SVs were identified in 5.4% of cases (79/1,462), of which 80% were uniquely detectable by srGS compared to standard cytogenetic techniques. For 96 families (including 10 families with a heterozygous variant observed in a known recessive gene of clinical relevance), we performed lrGS with methylation profiling, as well as long-read transcriptomic analyses in a subset of 20 trios. Analyses with lrGS yielded over 25,000 SVs per genome, 63% of which were not captured by srGS, along with an additional ~200 rare SNV/indels per genome not previously captured and 12 differentially methylated regions per genome. Among these, we identified only one diagnostic variant not interpreted by srGS, an apparently mosaic de novo SNV in CASK that was absent in the srGS callset due to allelic imbalance. No new diagnoses were supported by long-read transcriptomics or episignatures. In this well characterized rare disease cohort, the added diagnostic yield was thus 1.04% (1/96 families). Following a systematic literature review of prior lrGS studies, we find that most reported diagnoses were detectable by srGS and that our added diagnostic yield is consistent with those prior studies. These studies emphasize the significant impact of comprehensive SV discovery in rare disease cases and further demonstrate the power for increased discovery of novel genomic variation and episignatures from lrGS. Nonetheless, they also serve to temper expectations of dramatic diagnostic advances in rare disease patients until there is more extensive annotation of the functional and clinical impact of all coding and noncoding variation uniquely accessible to lrGS with extensive reference databases spanning highly repetitive genomic sequencing that could be enabled by this transformative technology.

Journal Article↗

A computer-assisted medical diagnostic consultation service. Implementation and prospective evaluation of a prototype.

STUDY OBJECTIVE: To evaluate the accuracy of a computer-aided consultation service using academic general internists and the Quick Medical Reference (QMR) diagnostic program: and to study the impact of the consultation on the diagnostic behavior of physicians caring for patients. DESIGN: Prospective study of the diagnostic accuracy of computer-aided consultation in 31 cases, as well as a prospective study of ward team diagnoses and opinions before and after consultation. SETTING: General medicine wards of two tertiary care centers. PARTICIPANTS: Thirty-one patients identified as posing a diagnostic challenge and meeting eligibility criteria, as well as the housestaff caring for these patients. MEASUREMENTS AND MAIN RESULTS: After 6 months follow-up, diagnoses were established in 20 of 31 cases. The diagnostic sensitivity of the computer-assisted diagnoses, 85% (95% CI, 56% to 97%), was similar to that of the consult service physicians, 80% (95% CI, 55% to 94%), but better than that of the ward teams, 60% (95% CI, 33% to 81%; P = 0.03 using the binomial test). The consultation influenced the postconsultation differential diagnoses of the ward teams in 26 of the 31 cases (95% CI, 92% to 95%). House officers rated the consultation service as being educationally helpful in 25 of the 31 cases (95% CI, 62% to 94%). CONCLUSIONS: Computer-aided diagnostic consultation, when provided by physicians familiar with the limitations of the system and capable of overriding inappropriate suggestions, was both accurate and educationally helpful in most cases. The system provided reasonable diagnostic suggestions not previously considered by the ward teams and these suggestions were valued sufficiently to cause alteration of the original differential diagnoses.

Diagnosis, Computer-Assisted↗

Diagnostic utility of ultrasonography of leg veins in patients suspected of having pulmonary embolism.

BACKGROUND: The standard diagnostic approach in patients suspected of having pulmonary embolism starts with perfusion-ventilation lung scanning. If the resulting scan is not diagnostic, pulmonary angiography should be done. The use of tests for deep venous thrombosis has been advocated as an adjunct to establishing the diagnosis of pulmonary embolism, but no prospective studies have provided adequate information about the value of these tests. OBJECTIVE: To determine the accuracy and potential clinical utility of compression ultrasonography in the diagnosis of pulmonary embolism. DESIGN: Prospective cohort study with blinded assessment of ultrasonographic results. SETTING: Teaching hospital. PATIENTS: 397 consecutive inpatients and outpatients in whom pulmonary embolism was clinically suspected. MEASUREMENTS: Sensitivity and specificity of compression ultrasonography. Perfusion-ventilation scanning and angiography were the conjoint gold standard for determining the presence or absence of pulmonary embolism. Also calculated were the number of angiograms and lung scans avoided and the number of patients unnecessarily treated when compression ultrasonography was included in the diagnostic strategy. RESULTS: The overall sensitivity of compression ultrasonography for deep venous thrombosis in patients with pulmonary embolism was 29% (95% CI 22% to 37%); the specificity was 97% (CI, 94% to 99%). Adding ultrasonography to the diagnostic approach before lung scanning would avoid approximately 14% of lung scans and 9% of angiograms but would lead to unnecessary treatment of 13% of patients who have an abnormal ultrasonographic result (2% to 4% of all those receiving anticoagulation). When compression ultrasonography is done only in patients with a nondiagnostic lung scan, 9% of angiographies are prevented at the cost of unnecessarily treating 26% of patients who have an abnormal ultrasonographic result (2% of all patients receiving anticoagulation). CONCLUSION: The diagnostic value of compression ultrasonography for the detection of deep venous thrombosis in patients suspected of having pulmonary embolism is limited; the gain in diagnostic efficiency obtained through the use of ultrasonography may be offset by a loss in diagnostic accuracy.

Adolescent↗

Aptamers: an emerging class of molecules that rival antibodies in diagnostics.

Antibodies, the most popular class of molecules providing molecular recognition needs for a wide range of applications, have been around for more than three decades. As a result, antibodies have made substantial contributions toward the advancement of diagnostic assays and have become indispensable in most diagnostic tests that are used routinely in clinics today. The development of the systematic evolution of ligands by exponential enrichment (SELEX) process, however, made possible the isolation of oligonucleotide sequences with the capacity to recognize virtually any class of target molecules with high affinity and specificity. These oligonucleotide sequences, referred to as "aptamers", are beginning to emerge as a class of molecules that rival antibodies in both therapeutic and diagnostic applications. Aptamers are different from antibodies, yet they mimic properties of antibodies in a variety of diagnostic formats. The demand for diagnostic assays to assist in the management of existing and emerging diseases is increasing, and aptamers could potentially fulfill molecular recognition needs in those assays. Compared with the bellwether antibody technology, aptamer research is still in its infancy, but it is progressing at a fast pace. The potential of aptamers may be realized in the near future in the form of aptamer-based diagnostic products in the market. In such products, aptamers may play a key role either in conjunction with, or in place of, antibodies. It is also likely that existing diagnostic formats may change according to the need to better harness the unique properties of aptamers.

Antibodies↗

Requirements for appropriate evaluation of diagnostic tests in suspected pulmonary embolism.

In contrast to the development of new drugs, strict guidelines for the development of new diagnostic methods do not exist. A diagnostic test can be made available without proper evaluation of its clinical utility, which can lead to its premature introduction and inappropriate use. In this review suggestions are made regarding the criteria that should be met during the various phases of development of new diagnostic techniques. It is suggested that a new diagnostic test should only be implemented in routine clinical use after all phases of development have been properly performed with good results. Several diagnostic tests for pulmonary embolism (pulmonary angiography, ventilation-perfusion scintigraphy, D-dimer assays, and spiral computed tomography), and the studies evaluating them, are thereafter reviewed. It is concluded that present pulmonary angiography and ventilation-perfusion scintigraphy are the only properly evaluated diagnostic tests for pulmonary embolism. Although new developments, such as D-dimer assays and the spiral computed tomographic scan are certainly promising, further studies are needed to determine their real value and safety in the diagnostic work-up of patients suspected of pulmonary embolism.

Angiography↗

The diagnostic headache diary--a headache expert system.

The purpose with the headache expert system was to develop a diagnostic and educational tool for the general practitioners (GP), in order to improve their management of headache disorders. This chapter describes the diagnostic headache diary, an expert system intended for education and diagnosing headache disorders. The diagnostic headache diary can be printed and used by headache patients at home to record their headache attacks and medicine consumption by a day to day basis. It can also be used by the GP at the clinic in order to provide the headache diagnoses. The diagnostic headache diary was written in the programming language Delphi and implemented as a stand-alone Windows 95 program. It was integrated as one of five modules in the headache tutorial described in another chapter of this book. The diagnostic headache diary consists of four modules: Patient data, diary, medication and diagnosis. Configured around a database, the diagnostic headache diary allows entries of several patients and search facilities. The diagnostic headache diary was tested and validated by entering expert-diagnosed data from different headache disorders which where compared to the computer generated diagnoses.

Diagnosis, Computer-Assisted↗

Otitis media in children: use of diagnostic tools by family practice residents.

BACKGROUND AND OBJECTIVES: Although otitis media is a common problem in primary care, little is known about the use of diagnostic tools such as pneumatic otoscopy, tympanometry, acoustic reflectometry, or tympanocentesis by family physicians in training. METHODS: This was a self-reported observational study of family practice residents' use of otitis media diagnostic tools. Twenty-three family practice programs in Texas and Oklahoma were surveyed during November and December 2000. Residents were asked about their use of diagnostic tools, and, if tools were not used, they were asked the reason for not using them. Residents were also asked about the criteria they used to diagnose otitis media, and their responses were compared to criteria recommended by national guideline panels. RESULTS: The response rate was 61% (n = 316). The percentage of residents using pneumatic otoscopy was 66%, tympanometry 29%, acoustic reflectometry 2%, and tympanocentesis 0%. The most common reasons cited for not using tools were lack of training or unavailability of equipment. Fifty-five percent of family practice residents do not report pneumatic otoscopy for diagnosing otitis media and thus did not use recommended criteria. Faculty training of residents in the use of diagnostic tools was associated with a higher rate of using these tools. DISCUSSION: Few residents believed that diagnostic tools had no value in the diagnosis of otitis media, but lack of training or equipment problems were reported as contributing to their not using these tools. Half of family practice residents may be inadequately diagnosing middle ear problems since they did not report that pneumatic otoscopy was necessary for diagnosing otitis media. Because training was associated with higher rates of using appropriate diagnostic tools, family medicine faculty can play a significant role in improving the residents' diagnostic skills.

Acoustic Impedance Tests↗

Diagnostic accuracy and perforation rate in appendicitis: association with age and sex of the patient and with appendicectomy rate.

OBJECTIVE: To see if diagnostic accuracy and perforation rate in acute appendicitis is associated with age and sex of the patients and with the appendicectomy rate. DESIGN: Retrospective study of consecutive patients from a defined population. Study of associations between diagnostic accuracy and perforation rate and appendicectomy rate in published reports. SETTING: Jönköping county, Sweden. SUBJECTS: 3,029 patients operated on for suspected acute appendicitis from 1984-1989. MAIN OUTCOME MEASURES: Findings at laparotomy for acute appendicitis, confirmed with histological examination in 83% of the cases. RESULTS: Diagnostic accuracy was low at the extremes of age and in women (60% compared with 79% in men, p less than 0.001). When all intra-abdominal conditions were considered the percentage of negative laparotomies among women (24%) was twice that among men (12%, p less than 0.001). This difference between the sexes was also seen in nonfertile ages. Perforation rate was higher among men (18% compared with 13%, p less than 0.01) and at extremes of age. According to correlation analysis of published reports the perforation rate is unrelated to either diagnostic accuracy or appendicectomy rate while diagnostic accuracy is inversely associated with the appendicectomy rate. CONCLUSION: A low diagnostic accuracy is a problem mainly at extremes of age and in females. A low appendicectomy rate is associated with a high diagnostic accuracy, while the perforation rate is unaffected. A conservative attitude to exploration therefore seems justified.

Adult↗

Application of a diagnostic algorithm for inherited thrombocytopenias to 46 consecutive patients.

BACKGROUND AND OBJECTIVES: The Italian Gruppo di Studio delle Piastrine recently developed a diagnostic algorithm to assist clinicians in the diagnosis of inherited thrombocytopenias. This algorithm is based on the simplest possible diagnostic investigations and can also be used in centers that are not highly specialized. The aim of the present study was to validate this diagnostic algorithm by applying it to a case series of genetic thrombocytopenias. DESIGN AND METHODS: The diagnostic algorithm was applied retrospectively to 46 consecutive patients observed during the last five years at a single institution. Twenty-eight were affected by defined illnesses or their variants, while 18 had a disorder that did not fit the criteria for any known genetic thrombocytopenia. The study was based on the evaluation of clinical records and laboratory tests. RESULTS: The diagnostic algorithm recognized: 4 homozygous and 4 heterozygous Bernard-Soulier syndromes, 11 MYH9-related diseases, one von WillebrandOs disease type 2B, one gray platelet syndrome and one X-linked thrombocytopenia with thalassemia. Moreover, it identified 4 patients with the clinical and laboratory features of heterozygous Bernard-Soulier syndrome not caused by mutations in the coding region of the GPIbalpha, GPIbbeta, GPIX or GPV genes, and two patients with the clinical phenotype of MYH9-related disease but without MYH9 mutations. Since the diagnostic flow chart did not allow prompt recognition of two subjects with MYH9-related disease, we introduced a small change to the previously proposed flow chart to obviate this defect. INTERPRETATION AND CONCLUSIONS: The diagnostic algorithm correctly diagnosed 26 of 28 patients with known disorders or phenotypic variants of known disorders. By a simple modification of the investigation sequence, its sensitivity reached 100%. The algorithm also identified 18 patients with new, as yet uncharacterized forms of genetic thrombocytopenia.

Algorithms↗

Diagnostic accuracy of atypical p-ANCA in autoimmune hepatitis using ROC- and multivariate regression analysis.

INTRODUCTION: Antineutrophil cytoplasmic antibodies (atypical p-ANCA) are detected at high prevalence in sera from patients with autoimmune hepatitis (AIH), but their diagnostic relevance for AIH has not been systematically evaluated so far. METHODS: Here, we studied sera from 357 patients with autoimmune (autoimmune hepatitis n=175, primary sclerosing cholangitis (PSC) n=35, primary biliary cirrhosis n=45), non-autoimmune chronic liver disease (alcoholic liver cirrhosis n=62; chronic hepatitis C virus infection (HCV) n=21) or healthy controls (n=19) for the presence of various non-organ specific autoantibodies. Atypical p-ANCA, antinuclear antibodies (ANA), antibodies against smooth muscles (SMA), antibodies against liver/kidney microsomes (anti-Lkm1) and antimitochondrial antibodies (AMA) were detected by indirect immunofluorescence microscopy, antibodies against the M2 antigen (anti-M2), antibodies against soluble liver antigen (anti-SLA/LP) and anti-Lkm1 by using enzyme linked immunosorbent assays. To define the diagnostic precision of the autoantibodies, results of autoantibody testing were analyzed by receiver operating characteristics (ROC) and forward conditional logistic regression analysis. RESULTS: Atypical p-ANCA were detected at high prevalence in sera from patients with AIH (81%) and PSC (94%). ROC- and logistic regression analysis revealed atypical p-ANCA and SMA, but not ANA as significant diagnostic seromarkers for AIH (atypical p-ANCA: AUC 0.754+/-0.026, odds ratio [OR] 3.4; SMA: 0.652+/-0.028, OR 4.1). Atypical p-ANCA also emerged as the only diagnostically relevant seromarker for PSC (AUC 0.690+/-0.04, OR 3.4). None of the tested antibodies yielded a significant diagnostic accuracy for patients with alcoholic liver cirrhosis, HCV or healthy controls. CONCLUSIONS: Atypical p-ANCA along with SMA represent a seromarker with high diagnostic accuracy for AIH and should be explicitly considered in a revised version of the diagnostic score for AIH.

Adolescent↗

[Diagnostic application of serum protein pattern and artificial neural network software in breast cancer].

BACKGROUND & OBJECTIVE: The progress in proteomics provides a novel platform for early diagnosis of cancer, and screening for new tumor biomarkers. This study was designed to develop and evaluate a diagnostic model of breast cancer with surface enhanced laser desorption/ionization-time of flight-mass spectrometry (SELDI-TOF-MS) ProteinChip array technology and artificial neural network software. METHODS: SELDI-TOF-MS ProteinChip was used to detect serum protein patterns of 49 patients with breast cancer, and 33 healthy women. Diagnostic model was developed, and validated using artificial neural network software. RESULTS: An intact diagnostic model from all 253 discrepant protein peaks, and a terse model from the top-scored 4 peaks were built. The diagnostic sensitivity, and specificity of the intact model were 83.33% (15/18), and 88.89% (8/9)u the detection rates of breast cancer of stage I, and stage II-IV using the intact model were 90.00% (9/10), and 75.00% (6/8). The diagnostic sensitivity, and specificity of the terse model were 76.47% (13/17), and 90.00% (9/10)u the detection rates of breast cancer of stage I, and stage II-IV using the terse model were 100.00% (3/3), and 71.43% (10/14). The diagnostic values of these 2 models were similar (P>0.05). Their diagnostic abilities to breast cancer of stage I were not worse than those to breast cancer of stage II-IV (P>0.05). CONCLUSION: High sensitivity and specificity achieved by this method show great potential for early diagnosis of breast cancer, and screening for new tumor biomarkers.

Adult↗

Comparison of the diagnostic value of local Widal slide test with imported Widal slide test.

A laboratory study comparing the Widal slide agglutination test using local antigens produced by Mekar Jaya Diagnostica (SAT-MJD) with imported antigens (Murex, Abbott) was carried out on 55 sera of typhoid fever patients with positive blood culture and 56 sera of non-typhoid febrile patients. The SAT-MJD antigens consisted of a mixture of 5 different phage-types of S. typhi dominantly found in Indonesia. This study revealed the following results: the diagnostic sensitivity of local and imported antigens was 83.93%, the diagnostic specificity of local antigens was higher than the imported antigens ie 82.14% compared with 64.28%, the diagnostic efficiency of local antigens was 82.88% compared with 73.87% of the imported antigens. The diagnostic positive and negative predictive values of the local antigens were 80.70% and 83.63%, respectively. The imported antigen revealed diagnostic positive and negative predictive values of 69.69% and 80%, respectively. The diagnostic specificity and efficiency of local antigens were significantly different (p < 0.02 and p < 0.05) from the imported antigens. The local antigens have some advantages. There was no variation in within-run and between-day test, compared with a 6.6% variation shown by the imported antigen. The test results obtained 5 minutes after mixing the serum with antigens reduced the possibility of false-positive and false-negative results. The cost of local antigens is lower than the imported antigens. Based on these data, the Widal SAT-MJD has a reliable diagnostic value and can be used in small laboratories, such as primary health centers (Puskesmas).

Adult↗

[Evaluation of diagnostic criteria of syphilitic infection by means of gas chromatography and mass-spectrometry].

In order to estimate possibility of chromatographic criteria application in diagnostics of syphilitic infection, the authors researched in three directions: evaluation of dysmetabolism of carbohydrate, lipid and amino acid components in patients' serum; search of signal compounds that serve as microbe "cooperative sensitivity" activators (lactones, quinolones, furan boron ethers) with evaluation of the risk of luetic infection generalization; indication of organ lesion markers (the brain, liver, bone structures). The factor analysis performed by the researchers allowed to determine priorities of clinical, laboratory and chromatographic data according to their value. The diagnostic value of various diagnostic chromatographic criteria was estimated as follows: the diagnostic sensitivity was 79.6% to 97.2%, the diagnostic specificity was 50.0% to 92.7%, the positive diagnostic predictability was 61.8% to 94.7% and the negative diagnostic predictability was 60.9% to 95.1%.

Amino Acids↗