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Diagnostic Setting (diagnostic + setting)

Distribution by Scientific Domains

Medical Sciences	50%
Life Sciences	50%

Selected Abstracts

Immunohistochemical staining for calretinin is useful in the diagnosis of ovarian sex cord,stromal tumours

HISTOPATHOLOGY, Issue 5 2001
W G McCluggage
Immunohistochemical staining for calretinin is useful in the diagnosis of ovarian sex cord,stromal tumours Aims:,Ovarian sex cord,stromal tumours are a heterogeneous group of neoplasms which may be confused morphologically with a wide variety of tumours. Calretinin positivity has previously been demonstrated in a small number of ovarian sex cord,stromal tumours. The aim of this study was to investigate calretinin staining in a series of these tumours and their histological mimics in order to determine the value of calretinin staining in a diagnostic setting. Methods and results:,Seventy-two neoplasms, including 37 ovarian sex cord,stromal tumours and 35 miscellaneous neoplasms which may enter into the differential diagnosis, were stained with a commercially available polyclonal antibody against calretinin. All sex cord,stromal tumours exhibited positivity except for a single fibrothecoma. In this group of tumours staining was generally diffuse and strong. Small numbers of the miscellaneous group of neoplasms exhibited positivity but this tended to be focal and weak, although this was not always the case. There was consistent strong positive staining of granulosa cells in follicular cysts and corpora lutea. There was also positive staining of luteinized stromal cells in two cases of ovarian stromal hyperplasia and hyperthecosis. Conclusions:,Calretinin is a sensitive immunohistochemical marker of ovarian sex cord,stromal tumours and may be useful in a diagnostic setting. However, the value is somewhat limited since occasional neoplasms which enter into the morphological differential diagnosis may be positive. Be that as it may, calretinin positivity may be of value in the diagnosis of an ovarian sex cord,stromal tumour and its differentiation from other neoplasms. In this regard, calretinin should always be used as part of a larger panel. [source]

Mean age-of-onset of familial alzheimer disease caused by presenilin mutations correlates with both increased A,42 and decreased A,40,,§

HUMAN MUTATION, Issue 7 2006
Samir Kumar-Singh
Abstract The varied ways in which mutations in presenilins (PSEN1 and PSEN2) affect amyloid b precursor protein (APP) processing in causing early-onset familial Alzheimer disease (FAD) are complex and not yet properly understood. Nonetheless, one useful diagnostic marker is an increased ratio of Ab42 to Ab40 (Ab42/Ab40) in patients' brain and biological fluids as well as in transgenic mice and cells. We studied Ab and APP processing for a set of nine clinical PSEN mutations on a novel and highly reproducible enzyme-linked immunosorbent assay (ELISA)-based in vitro method and also sought correlation with brain Ab analyzed by image densitometry and mass spectrometry. All mutations significantly increased Ab42/Ab40 in vitro by significantly decreasing Ab40 with accumulation of APP C-terminal fragments, a sign of decreased PSEN activity. A significant increase in absolute levels of Ab42 was observed for only half of the mutations tested. We also showed that age-of-onset of PSEN1-linked FAD correlated inversely with Ab42/Ab40 (r=,0.89; P=0.001) and absolute levels of Ab42 (r=,0.83; P=0.006), but directly with Ab40 levels (r=0.69; P=0.035). These changes also partly correlated with brain Ab42 and Ab40 levels. Together, our data suggested that Ab40 might be protective by perhaps sequestering the more toxic Ab42 and facilitating its clearance. Also, the in vitro method we describe here is a valid tool for assaying the pathogenic potential of clinical PSEN mutations in a molecular diagnostic setting. Hum Mutat 27(7), 686,695, 2006. Published 2006 Wiley-Liss, Inc. [source]

Chromosomal anomalies on 6p25 in iris hypoplasia and Axenfeld-Rieger syndrome patients defined on a purpose-built genomic microarray,

HUMAN MUTATION, Issue 1 2004
Rosemary Ekong
Abstract In many inherited diseases, the same phenotype can be produced both by single-base changes and by large deletions, or in some cases by duplications. Routine high-throughput sequencing can now detect small mutations relatively easily in a diagnostic setting, but deletions and duplications in the 50,500-kb region remain a more difficult problem. We have explored the application of array-CGH to the detection of such changes on a set of 20 samples consisting of patients with eye diseases associated with changes on chromosome 6p25 together with unaffected individuals, as well as two samples from tuberous sclerosis 2 (TSC2)-affected patients. We developed a microarray consisting of degenerate oligonucleotide primer (DOP)-PCR products from 260 human genomic clones, including BACs, PACs, and cosmids. In a masked study, chromosome changes in patients with iris hypoplasia (duplication) and Axenfeld-Rieger syndrome (deletion) were unequivocally distinguished from controls. Of the 20 6p25 samples analyzed, 19 were analyzed correctly (10 duplication cases, two deletions, and seven normals), while one individual failed to give a result because of poor hybridization. The extent of the duplication or deletion estimated was similar to that obtained by independent and much more time-consuming FISH experiments. On the other hand, deletions in the two TSC2 -affected samples, previously mapped by DNA molecular combing, were not detected on the array, possibly due to the repeat content of that region. Excluding the 16p13 cosmids, consistent results were obtained from all other cosmid clones; the potential for producing affordable disease-specific diagnostic microarray as an adjunct to diagnosis is discussed. Hum Mutat 24:76,85, 2004. © 2004 Wiley-Liss, Inc. [source]

Improved detection of clonality in cutaneous T-cell lymphomas using laser capture microdissection

JOURNAL OF CUTANEOUS PATHOLOGY, Issue 8 2003
Amir S. Yazdi
Background:, The diagnosis of cutaneous T-cell lymphoma is a challenge for both the pathologist and the clinician. This is particularly true for distinguishing early-stage mycosis fungoides from dermatitis. In this clinical setting, the presence of a clonal T-cell population supports lymphoma. Methods:, Usually, routinely processed paraffin-embedded material is available for gene rearrangement analysis, and polymerase chain reaction (PCR)-based methods to assess clonality can be performed. One drawback of this approach is that sensitivity is suboptimal in biopsy specimens in which the lymphocytic infiltrate represents only a small percentage of all cells present. Another drawback is that DNA extraction from routinely processed, paraffin-embedded tissue is a time-consuming and labor-intensive procedure which can take up to 5 days in our laboratory. To bypass these problems, we used laser capture microdissection (LCM) to obtain lymphocytic infiltrates from tissue sections of formalin-fixed, paraffin-embedded skin biopsy specimens. This approach allows for more specific PCR assessment of the lymphocytic infiltrate and for rapid DNA extraction and PCR analysis. Results:, Using the LCM approach, we could demonstrate clonal T-cell receptor , gene rearrangements in biopsy specimens that did not show clonality using DNA extracted by conventional methods from full tissue sections. In addition, DNA extraction and PCR analysis can be performed in 11 h. Conclusion:, In conclusion, applying LCM to clonality analysis of cutaneous lymphocytic infiltrates is rapid and more sensitive than conventional methods, and we recommend introducing this approach into the routine diagnostic setting. [source]

Protein profiling in pathology: Analysis and evaluation of 239 frozen tissue biopsies for diagnosis of B-cell lymphomas

PROTEOMICS - CLINICAL APPLICATIONS, Issue 5 2010
Corine Jansen
Abstract Purpose: We determined the potential value of protein profiling of tissue samples by assessing how precise this approach enables discrimination of B-cell lymphoma from reactive lymph nodes, and how well the profiles can be used for lymphoma classification. Experimental design: Protein lysates from lymph nodes (n=239) from patients with the diagnosis of reactive hyperplasia (n=44), follicular lymphoma (n=63), diffuse large B-cell lymphoma (n=43), mantle cell lymphoma (n=47), and chronic lymphocytic leukemia/small lymphocytic B-cell lymphoma (n=42) were analysed by SELDI-TOF MS. Data analysis was performed by (i) classification and regression tree-based analysis and (ii) binary and polytomous logistic regression analysis. Results: After internal validation by the leave-one-out principle, both the classification and regression tree and logistic regression classification correctly identified the majority of the malignant (87 and 96%, respectively) and benign cases (73 and 75%, respectively). Classification was less successful since approximately one-third of the cases of each group were misclassified according to the histological classification. However, an additional mantle cell lymphoma case that was misclassified as chronic lymphocytic leukemia/small lymphocytic B-cell lymphoma initially was identified based on the protein profile. Conclusions and clinical relevance: SELDI-TOF MS protein profiling allows for reliable identification of the majority of malignant lymphoma cases; however, further validation and testing robustness in a diagnostic setting is needed. [source]

Cost and cost-effectiveness of digital mammography compared with film-screen mammography in Australia

AUSTRALIAN AND NEW ZEALAND JOURNAL OF PUBLIC HEALTH, Issue 5 2009
Shuhong Wang
Abstract Objective: A systematic review assessed the relative safety and effectiveness of digital mammography compared with film-screen mammography. This study utilised the evidence from the review to examine the economic value of digital compared with film-screen mammography in Australia. Methods: A cost-comparison analysis between the two technologies was conducted for the overall population for the purposes of breast cancer screening and diagnosis. In addition, a cost-effectiveness analysis was conducted for the screening subgroups where digital mammography was considered to be more accurate than film-screen mammography. Results: Digital mammography in a screening setting is $11 more per examination than film-screen mammography, and $36 or $33 more per examination in a diagnostic setting when either digital radiography or computed radiography is used. In both the screening and diagnostic settings, the throughput of the mammography system had the most significant impact on decreasing the incremental cost/examination/year of digital mammography. Conclusion: Digital mammography is more expensive than film-screen mammography. Whether digital mammography represents good value for money depends on the eventual life-years and quality-adjusted life-years gained from the early cancer diagnosis. Implications: The evidence generated from this study has informed the allocation of public resources for the screening and diagnosis of breast cancer in Australia. [source]

The impact of cytomorphology, cytogenetics, molecular genetics, and immunophenotyping in a comprehensive diagnostic workup of myelodysplastic syndromes

CANCER, Issue 19 2009
Ulrike Bacher MD
Abstract BACKGROUND: Because of limited reproducibility of morphologic features, the morphological categorization of initial myelodysplastic syndromes (MDS) cases remains a major task in a diagnostic setting. METHODS: To further evaluate the role of additional diagnostic methods for suspected early MDS, the authors analyzed 1965 cases with unclear cytopenia where at least cytomorphology and immunophenotyping were performed in parallel, combined with cytogenetics and molecular genetics. RESULTS: In 353 patients, both methods diagnosed malignant/nonmalignant disease other than MDS, and 557 patients had MDS-refractory anemia with excess of blasts/chronic myelomonocytic leukemia. The remaining 1055 patients (53.7%), where early MDS/reactive cytopenia had to be assumed, were categorized into 6 groups depending on cytomorphology/immunophenotyping results for or against MDS. In 659 of 1055 cases (62.4%) with suspected initial MDS, cytomorphology and immunophenotyping were concordant in the categorization of MDS/non-MDS. Cytogenetics, available in 951 of 1055 patients, revealed the highest frequency of aberrant karyotypes when both cytomorphology and immunophenotyping proposed MDS (63 of 227; 27.8%). But also in the groups where either cytomorphology or immunophenotyping showed evidence of MDS, aberrant karyotypes were found in 6% to 14% of patients. Even when both morphology and immunophenotyping showed no MDS, 11 of 208 (5.3%) had cytogenetic aberrations. RUNX1/AML1 mutation screening was positive in 15% in the latter group. NRAS, MLL -PTD, NPM1, and JAK2V617F were detected in low frequencies, confirming MDS diagnosis in the respective cases. CONCLUSIONS: This report outlines the power of a combined diagnostic approach for suspected initial cases of MDS including immunophenotyping, cytogenetics, and molecular genetics with selected markers in addition to cytomorphology. Diagnostic algorithms should be developed, and immunophenotyping should be further validated for this specific indication. Cancer 2009. © 2009 American Cancer Society. [source]

UMD-predictor, a new prediction tool for nucleotide substitution pathogenicity,application to four genes: FBN1, FBN2, TGFBR1, and TGFBR2,

HUMAN MUTATION, Issue 6 2009
Mélissa Yana Frédéric
Abstract Approximately half of gene lesions responsible for human inherited diseases are due to an amino acid substitution, showing that this mutational mechanism plays a large role in diseases. Distinguishing neutral sequence variations from those responsible for the phenotype is of major interest in human genetics. Because in vitro validation of mutations is not always possible in diagnostic settings, indirect arguments must be accumulated to define whether a missense variation is causative. To further differentiate neutral variants from pathogenic nucleotide substitutions, we developed a new tool, UMD-Predictor®. This tool provides a combinatorial approach that associates the following data: localization within the protein, conservation, biochemical properties of the mutant and wild-type residues, and the potential impact of the variation on mRNA. To evaluate this new tool, we compared it to the SIFT, PolyPhen, and SNAP software, the BLOSUM62 and Yu's Biochemical Matrices. All tools were evaluated using variations from well-validated datasets extracted from four UMD,LSDB databases (UMD,FBN1, UMD,FBN2, UMD,TGFBR1, and UMD,TGFBR2) that contain all published mutations of the corresponding genes, that is, 1,945 mutations, among which 796 different substitutions corresponding to missense mutations. Our results show that the UMD-Predictor® algorithm is the most efficient tool to predict pathogenic mutations in this context with a positive predictive value of 99.4%, a sensitivity of 95.4%, and a specificity of 92.2%. It can thus enhance the interpretation of variations in these genes, and could easily be applied to any other disease gene through the freely available UMD® generic software (http://www.umd.be). Hum Mutat 30:1,8, 2009. © 2009 Wiley-Liss, Inc. [source]

Novel PlexorÔ SNP genotyping technology: comparisons with TaqMan® and homogenous MassEXTENDÔ MALDI-TOF mass spectrometry,

HUMAN MUTATION, Issue 9 2007
E.A. Tindall
Abstract Analysis of SNPs for association, linkage, haplotype, and pharmacogenetic studies has led to a dramatic increase in the number and evolution of medium- to high-throughput genotyping technologies. This study introduces PlexorÔ as a new method for medium-throughput (single SNP) genotyping. We compare this fluorescent-based chemistry for call rate, accuracy, affordability, throughput, and overall efficiency against two commonly used technologies. These include fluorescent-based TaqMan® allelic discrimination for single SNP analysis (medium-throughput) and the homogenous MassEXTENDÔ (hMEÔ) chemistry using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry for multiple SNP analysis (high-throughput). Analysis of 11 SNPs, including all six possible nucleotide substitutions, showed PlexorÔ to be highly comparable for both call rate (94.7%) and accuracy (99.2%) to the TaqMan® (94.6% and 99.8%, respectively) and hMEÔ (91.9% and 98.1%, respectively) chemistries. We demonstrate that this novel method is an efficient, cost-effective alternative to TaqMan® genotyping commonly used in diagnostic settings. Hum Mutat 28(9), 922,927, 2007. © 2007 Wiley-Liss, Inc. [source]