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PubMed2006

A new classification of HLA-DRB1 alleles differentiates predisposing and protective alleles for rheumatoid arthritis structural severity.

OBJECTIVE: A new classification of HLA-DRB1 alleles supporting the shared epitope hypothesis of rheumatoid arthritis (RA) susceptibility was recently introduced. We investigated the relevance of this classification in terms of the structural severity of RA. METHODS: The study group comprised 144 patients who were included in a prospective longitudinal cohort of French Caucasoid patients with early RA. Progression of the total radiographic damage score (Sharp/van der Heijde method) was used to quantify the structural severity of RA after 4 years of followup. HLA-DRB1 typing and subtyping were performed by polymerase chain reaction, using a panel of sequence-specific oligonucleotide probes. HLA-DRB1 alleles were classified according to the above-mentioned new system. The association between the HLA-DRB1 allele groups (S1, S2, S3P, S3D, and X) and the structural severity of RA was analyzed with nonparametric statistical tests. RESULTS: The presence of S2 alleles (HLA-DRB1*0401 and HLA-DRB1*1303) was associated with severe forms of RA (P = 0.004); a significant dose effect was observed (P = 0.01). The presence of S3D alleles (HLA-DRB1*11001, HLA-DRB1*1104, HLA-DRB1*12, and HLA-DRB1*16) was associated with benign forms of RA (P < 0.0001), and a significant dose effect was observed (P < 0.01). CONCLUSION: The studied classification of HLA-DRB1 alleles is relevant in terms of RA outcomes. Compared with a previously described classification system, this system differentiates predisposing (S2) and protective (S3D) alleles for RA structural severity, which, respectively, correspond to KRRAA and DRRAA amino acid patterns at position 70-74 of the third hypervariable region of the HLA-DRbeta chain.

Alleles↗
PubMed2002

Evaluation of the Society for Coronary Angiography and Interventions' lesion classification system in 14,133 patients with percutaneous coronary interventions in the current stent era.

We recently showed that the ACC/AHA coronary lesion classification could be simplified with no loss of predictive value (SCAI I = patent/non-C; SCAI II = patent/C; SCAI III = occluded/non-C; SCAI IV = occluded/C). We now test this system in a database reflecting current stent usage. Data from 14,133 patients with single-native-vessel interventions recorded in the Society for Coronary Angiography and Interventions (SCAI) Registry from July 1996 to July 1999 were analyzed. Stents were used in 60.2% of procedures. Logistic models predicting angiographic success suggested a slight, clinically insignificant preference for the SCAI classification (c-statistic = 0.692 vs. 0.670). Models using clinical variables to predict major complications were superior to models using only lesion classification. Lesion characteristics were related to outcomes primarily in elective (not acute myocardial infarction) patients. In the current PCI device era, the simpler SCAI classification using 7 variables predicted interventional success and complications as well as or better than the ACC/AHA system requiring 26.

Aged↗
PubMed1998

Relationship between Joint National Committee-VI classification of hypertension and ambulatory blood pressure in patients with hypertension diagnosed by casual blood pressure.

BACKGROUND: White-coat hypertension has been diagnosed arbitrarily based on different criteria. In 1997, the Joint National Committee-VI (JNC-VI) reported a new classification of hypertension and strongly emphasized the importance of ambulatory blood pressure (ABP) monitoring. The report pronounced normal ABP values for the first time. HYPOTHESIS: The study's aim was to clarify the relationship between casual blood pressure (BP) and ABP of patients with essential hypertension in each stage of JNC-VI classification, and the prevalence of white-coat hypertension diagnosed by using JNC-VI normal ABP criteria. METHODS: Ambulatory blood pressure was monitored non-invasively in 232 patients with essential hypertension whose casual BP was > or = 140/90 mmHg. The patients were classified according to JNC-VI classification, and their casual BP was compared with ABP. The criterion of white-coat hypertension was defined as casual BP > or = 140/90 mmHg with normal ABP according to JNC-VI criteria (< 135/85 during daytime and < 120/75 during nighttime). RESULTS: Mean ABP increased as the stage advanced, and the differences between casual BP and ABP also increased. There were considerable overlaps in the distribution of ABP among stages. The prevalence of white-coat hypertension was 13% overall: 30% of the patients with isolated systolic hypertension, 19% of those in stage 1, 10% in stage 2, and 4% in stage 3. CONCLUSIONS: Classification of hypertension based on casual BP may not always correspond in severity to that based on ABP. Ambulatory blood pressure monitoring recommended by JNC-VI is very useful for the evaluation of hypertension to differentiate white-coat hypertension from true hypertension.

Adult↗
PubMed2002

The effects of the current World Health Organization/International Society of Urologic Pathologists bladder neoplasm classification system on urine cytology results.

BACKGROUND: Historically, the diagnostic accuracy of urine cytology for the detection of urothelial carcinoma has been low, particularly for low-grade lesions. In 1998, the World Health Organization and International Society of Urologic Pathologists (WHO/ISUP) established a new classification system for urothelial neoplasms. It has been postulated that the accuracy of urine cytology for the detection of low-grade carcinomas should improve, because the current WHO/ISUP system classifies bladder lesions that lack any significant cytologic atypia as papillary urothelial neoplasms of low malignant potential (PUNLMP). Also, the accuracy of urinary cytology for the detection of high-grade lesions is expected to decrease, because the criteria for high-grade lesions is lowered, placing most of the previous WHO Grade 2 tumors into the current high-grade carcinoma category. METHODS: One hundred bladder biopsies that were classified according to the previous WHO classification system were examined by one pathologist and were reclassified according to the new WHO/ISUP scheme. All biopsies had corresponding urine specimens that had been diagnosed previously by a different cytopathologists. The patients' previous WHO and current WHO/ISUP surgical diagnoses were compared with the corresponding urine cytology. In addition, cytospins obtained from 40 patients with a histologic diagnosis of low-grade urothelial carcinoma (n = 20 patients) and high-grade urothelial carcinoma (n = 20 patients) according to the WHO/ISUP classification system were reviewed to identify any outstanding cytologic features. RESULTS: According to the original WHO classification system, there were 26 patients with Grade 1 transitional cell carcinoma (TCC), 61 patients with Grade 2 TCC, and 13 patients with Grade 3 TCC. The corresponding cytology was positive in 11 of 26 Grade 1 tumors, 28 of 61 Grade 2 tumors, and 12 of 13 Grade 3 tumors. After the reclassification, there was 1 papilloma, 12 PUNLMP lesions, 50 low-grade urothelial carcinomas, and 37 high-grade carcinomas. The cytology was positive in 0 of 1 papillomas, 5 of 7 PUNLMP lesions, 18 of 50 low-grade carcinomas, and 28 of 37 high-grade carcinomas. In addition, morphologic uniformity and cytoplasmic homogeneity (50.0% and 45.0%, respectively) were seen more commonly in low-grade bladder tumors. CONCLUSIONS: The diagnostic accuracy of urine cytology for high-grade lesions decreased, as expected; however, cytologic detection of low-grade urothelial carcinomas was remarkably lower than expected. In addition, no outstanding cytologic features could be identified to make a definitive diagnosis.

Aged↗
PubMed1999

The relative role of the Child-Pugh classification and the Mayo natural history model in the assessment of survival in patients with primary sclerosing cholangitis.

The Child-Pugh classification is a simple, convenient prognostic measure in patients with liver cirrhosis. We investigated the relative role of the Child-Pugh classification and the Mayo model in the assessment of survival in patients with primary sclerosing cholangitis (PSC). Of the 173 patients described in the original Mayo PSC natural history model, 147 patients had sufficient information in the medical record to allow computation of the Child-Pugh score. We used our most recent modification of the Mayo model to compute the risk score, based on patient's age, serum levels of bilirubin, albumin, and aspartate aminotransferase and history of variceal bleeding. Using the risk score (R), patients were divided into the low- (R < 0), intermediate- (0 </= R < 2), and high-risk (R >/= 2) groups. Kaplan-Meier estimates and proportional hazards analysis were used to evaluate the two prognostic models. Although there was a statistically significant correlation between the Child-Pugh and Mayo risk scores, two-thirds of the patients had a Child-Pugh score of 5 or 6 and a relatively wide range of risk scores (-1.1-4.3). The probability of survival for 7 years in patients in the low-, intermediate-, and high-risk groups was 92%, 74%, and 40% for Child-Pugh class A (n = 96) and 100%, 62%, and 28% for Child-Pugh class B patients (n = 44), respectively. There were only a small number (n = 7) of Child-Pugh class C patients. In our age-adjusted multivariate analysis, each unit increase in the Mayo risk score was associated with a 2.5-fold increase in the risk of death (95% confidence interval: 1.8-3.4, P <.01), whereas Child-Pugh classification had no significant impact on survival (Child-Pugh B vs. A: risk ratio = 1.1 [95% confidence interval: 0.6-2.0]; Child-Pugh C versus A: risk ratio = 0.6 [95% confidence interval: 0. 2-1.8]). In contrast to the Child-Pugh classification, which was developed for advanced liver cirrhosis, the Mayo model provides valid survival information, particularly in patients early in the course of PSC.

Adult↗
PubMed2002

Molecular classification of borderline ovarian tumors using hierarchical cluster analysis of protein expression profiles.

Ovarian tumors range from benign to aggressive malignant tumors, including an intermediate class referred to as borderline carcinoma. The prognosis of the disease is strongly dependent on tumor classification, where patients with borderline tumors have much better prognosis than patients with carcinomas. We here describe the use of hierarchical clustering analysis of quantitative protein expression data for classification of this type of tumor. An accurate classification was not achieved using an unselected set of 1,584 protein spots for clustering analysis. Different approaches were used to select spots that were differentially expressed between tumors of different malignant potential and to use these sets of spots for classification. When sets of proteins were selected that differentiated benign and malignant tumors, borderline tumors clustered in the benign group. This is consistent with the biologic properties of these tumors. Our results indicate that hierarchical clustering analysis is a useful approach for analysis of protein profiles and show that this approach can be used for differential diagnosis of ovarian carcinomas and borderline tumors.

Adult↗
PubMed2006

Circulating MMP2 and MMP9 in breast cancer -- potential role in classification of patients into low risk, high risk, benign disease and breast cancer categories.

Matrix metalloproteinase (MMP) 2 and 9 are involved in cancer invasion and metastasis, and increased levels occur in serum and plasma of breast cancer (BC) patients. It is, however, unclear whether changes in serum levels can be exploited for early detection or classification of patients into different risk/disease categories. In our study, we measured concentration and activity of MMP2/9 in sera of 345 donors classified as low risk (Gail score <1.7), high risk (HR) (Gail score > or =1.7), benign disease or BC. Kruskal-Wallis and Mann-Whitney nonparametric tests showed that total-MMP2 concentration is higher in HR compared to control (p = 0.012), benign (p = 0.001) and cancer (p = 0.007). Active MMP2 (aMMP2) concentration is higher in control than benign and cancer (p < 0.001, respectively). Total and aMMP9 concentrations are higher in cancer than benign (p < 0.001, p = 0.002, respectively). Total-MMP2 and total-MMP9 activities are lower in control than benign (p < 0.001, p = 0.002, respectively) and cancer (p < 0.001, respectively). Total-MMP2 and MMP9 activities are also higher in cancer than benign (p = 0.004, p < 0.001) and HR (p = 0.008, p = 0.007, respectively). These results were not affected by age or inclusion/exclusion of donors with noninvasive cancer or atypical hyperplasia. Linear discriminant analysis revealed that HR donors are characterized by lower total-MMP2 and higher aMMP2. Overall group classification accuracy was 64.5%. Independent validation based on the leave-one-out cross validation approach gave an overall classification of 63%. Our study provides evidence supporting the potential role of serum MMP2/9 as biomarkers for breast disease classification.

Adult↗
PubMed1980

Difficulties encountered in the application of Clark classification and the Breslow thickness measurement in cutaneous malignant melanoma.

The purpose of this study was to analyse the reproducibility of Clark's classification and Breslow's measure of tumor thickness to determine if there is general agreement among pathologists regarding these parameters and whether these pathologists reach consistent conclusions concerning each slide. Three successive workshops including a panel of pathologists were held at Amsterdam, in May 1977; at Villejuif in June 1977, followed by circulation of slides and at Villejuif again, in June 1978, followed by slide projection. This was necessary because of the great divergencies of opinion noted at the first meeting at Amsterdam. These sessions gave a better understanding of the divergencies and finally indicated that general agreement could only be reached by slide presentation followed by discussion. Regarding histogenesis, agreement between pathologists was improved after discussion from 6/11 cases to 11/13 cases. Regarding the level, no initial agreement was reached (Amsterdam). At the second meeting an agreement was obtained in 4/13 cases and finally in 11/13 cases (Villejuif). Clark's classification is more difficult to use than Breslow's because it depends on a discontinuous variable, the choice of the infiltration level. Breslow's classification, on the other hand, is based on a continuous variable. Because of frequent discrepancies, the classification of patients into various therapeutic groups according to Clark's level and Breslow's thickness necessitates that all cases including in therapeutic trials be reviewed by a panel of pathologists.

Histological Techniques↗
PubMed1995

Incidence of cancer among New South Wales adolescents: which classification scheme describes adolescent cancers better?

This report has the dual purpose of describing patterns of cancer incidence among adolescents in New South Wales (NSW), Australia, and comparing adult and childhood cancer classification schemes. All cases of cancer incident between 1972 and 1991 in NSW residents aged 10-19 years were obtained from the population-based NSW Central Cancer Registry and coded according to Birch and Marsden (1987) in addition to routine coding by the Ninth Revision of the International Classification of Diseases. The average incidence rate for all cancers combined was 158 and 140 per million in males and females respectively. The Birch and Marsden category of "carcinomas and other epithelial neoplasms" comprised 22% of all cancers in male adolescents and 37% in females. Melanoma alone accounted for 16% of all cancers in males and 26% in females. Rates of leukaemias and central nervous system tumours were similar in the age groups 10-14 years and 15-19 years. By contrast, lymphomas, bone tumours (males only), soft tissue (males only), "germ-cell, trophoblastic and other gonadal tumours" and "carcinomas and other epithelial neoplasms" were more common in the older age group. The Birch and Marsden classification with its emphasis on morphology provided a clearer picture of some types of cancer which occurred frequently among teenagers. Cancers common in adults did occur in older adolescents but were less well described by the childhood scheme. Cancers of colon and lung were often of unusual histological type compared to adult tumours. It would appear appropriate to use the childhood classification scheme to describe cancer incidence in adolescent age groups, perhaps with minor modification.

Adolescent↗
PubMed2002

Histologic classification of ductal carcinoma in situ.

Prior to the current mammographic era, ductal carcinoma in situ (DCIS) usually presented as a large mass, was classified morphologically by architecture, and treated by mastectomy. The introduction of screening mammography led to an increase in the incidence of DCIS, a decrease in the average size of DCIS, and an increased emphasis on its heterogeneous nature. Thus, a reproducible and prognostically relevant classification system for DCIS is necessary. The ultimate goal of this classification is proper selection of patients for whom lumpectomy would suffice rather than mastectomy. Features to evaluate include: extent and size of disease, adequacy of resection margins, and histology. While none of the proposed histological classification systems were endorsed at the recent Consensus Conference on the Classification of DCIS, nuclear grade was the most important feature common to most of them. Architecture was given secondary importance. By definition, DCIS is a non-invasive clonal proliferation of epithelial cells originating in the terminal duct lobular unit, which would be expected to be monomorphic; however, it is the degree of nuclear pleomorphism that is primarily used to separate DCIS into low, intermediate, and high grades. Architecturally, DCIS has been divided into the following types: comedo, solid, cribriform, micropapillary, and papillary. Different architectural patterns and grades may be present in a given particular case; however, some combinations of patterns occur more frequently than others. Interobserver studies have shown nuclear grading to be interpreted with greater consistency than architecture, and nuclear grading methods have correlated with biological and molecular marker studies.

Carcinoma, Intraductal, Noninfiltrating↗
PubMed2005

Mixture model approach to tumor classification based on pharmacokinetic measures of tumor permeability.

PURPOSE: To categorize the disease severity of mammary tumors in an animal model through the application of a novel tumor permeability mixture model within a hierarchical modeling framework. MATERIALS AND METHODS: Thirty-six rats with mammary tumors of varying grade were imaged via dynamic contrast-enhanced (CE) MRI using albumin-(Gd-DTPA)30. Time-dependent contrast agent concentration curves for blood and tumor tissue were obtained and a mathematical model of microvascular blood-tissue exchange was developed under the hypothesis that endothelial integrity is disrupted in a manner proportional to the degree of malignancy, with benign tumors showing no disruption of the vasculature endothelium. This permeability model was incorporated into a statistical model for the benign and malignant tumor subgroups that enabled automatic subject classification. The structural and statistical models were implemented using the software Nonlinear Mixed Effects Modeling (NONMEM) to statistically separate subjects into the two subgroups. RESULTS: Individual tumor classifications (as benign or malignant) were evaluated against the Scarff-Bloom-Richardson microscopic scoring method as applied to the tumor histology of each subject. The model-based classification resulted in 90.9% sensitivity, 92.9% specificity, and 91.7% accuracy. CONCLUSION: Mixture model analysis provides a robust method for subject classification without user intervention and bias. Although the present results are promising, additional research is needed to further evaluate this technique for diagnostic purposes.

Animals↗
PubMed2002

Classification of proteins based on the properties of the ligand-binding site: the case of adenine-binding proteins.

Comparative analysis of protein binding sites for similar ligands yields information about conserved interactions, relevant for ligand affinity, and variable interactions, which are important for specificity. The pattern of variability can indicate new targets for a pharmacologically validated class of compounds binding to a similar site. A particularly vast group of therapeutically interesting proteins using the same or similar substrates are those that bind adenine-containing ligands. Drug development is focusing on compounds occupying the adenine-binding site and their specificity is an issue of paramount importance. We use a simple scheme to characterize and classify the adenine-binding sites in terms of their intermolecular interactions, and show that this classification does not necessarily correspond to protein classifications based on either sequence or structural similarity. We find that only a limited number of the different hydrogen bond patterns possible for adenine-binding is used, which can be utilized as an effective classification scheme. Closely related protein families usually share similar hydrogen patterns, whereas non-polar interactions are less well conserved. Our classification scheme can be used to select groups of proteins with a similar ligand-binding site, thus facilitating the definition of the properties that can be exploited to design specific inhibitors.

Adenine↗
PubMed2004

A simple topological representation of protein structure: implications for new, fast, and robust structural classification.

A topological representation of proteins is developed that makes use of two metrics: the Euclidean metric for identifying natural nearest neighboring residues via the Delaunay tessellation in Cartesian space and the distance between residues in sequence space. Using this representation, we introduce a quantitative and computationally inexpensive method for the comparison of protein structural topology. The method ultimately results in a numerical score quantifying the distance between proteins in a heuristically defined topological space. The properties of this scoring scheme are investigated and correlated with the standard Calpha distance root-mean-square deviation measure of protein similarity calculated by rigid body structural alignment. The topological comparison method is shown to have a characteristic dependence on protein conformational differences and secondary structure. This distinctive behavior is also observed in the comparison of proteins within families of structural relatives. The ability of the comparison method to successfully classify proteins into classes, superfamilies, folds, and families that are consistent with standard classification methods, both automated and human-driven, is demonstrated. Furthermore, it is shown that the scoring method allows for a fine-grained classification on the family, protein, and species level that agrees very well with currently established phylogenetic hierarchies. This fine classification is achieved without requiring visual inspection of proteins, sequence analysis, or the use of structural superimposition methods. Implications of the method for a fast, automated, topological hierarchical classification of proteins are discussed.

Amino Acid Sequence↗
PubMed2007

Improving the quality of patient care using reliability measures: a classification tree approach.

This paper considers the application and interpretation of new reliability measures for a classification tree-based medical risk assessment tool. Following the construction of a classification tree reliability measures may then be used to provide an estimate of the precision of the classification and the probability in each terminal node of the classification tree. Identification of unreliable nodes (those that have low precision) in this application may indicate patient groups requiring closer monitoring or scenarios in which further information about the patient is required, thereby providing medical practitioners with an avenue for more informed decision making.

Biometry↗
PubMedDate not supplied

Cancer staging: future directions for the TNM classification.

The major accomplishment of the 1987 edition of the TNM classification was the unification of criteria for all site classifications, namely, the elimination of all variations that had developed over the years. The main directions that TNM is taking for the future are 1) verification of published classifications, 2) classification of new sites and tumor types, 3) addressing the integration of nonanatomic factors with TNM to achieve prognostic grading, and 4) application of TNM beyond pure clinical-pathological aspects to assess methods of early detection, quality of care, and population trends.

Health Planning Guidelines↗
PubMed1993

Trypanosoma cruzi: correlation between karyotype variability and isoenzyme classification.

Forty-three Trypanosoma cruzi isolates from Chile and Colombia and three cloned stocks from Bolivia and Brazil were studied at the karyotype level by hybridization with four different parasite gene probes to chromosomes separated by pulsed-field gel electrophoresis. The results showed that classification of parasite isolates based on isoenzyme analysis at 12 or more genetic loci correlated with the classification obtained by molecular karyotype analysis. However, less correlation was found between molecular karyotypes and the zymodemes Z1, Z2Bra, Z2Bol, and Z3 based on analysis at only two genetic loci. All the four probes used in this study allowed differentiation between different T. cruzi stocks but the SAPA and the antigen 13 probes were most informative. Isolates which were unclassified at the isoenzyme level were also studied and in most cases similar hybridization patterns were observed as obtained with one or more isoenzyme-classified isolates. The results demonstrate the potential of using molecular karyotyping as a tool for classification. A few pulsed-field gel electrophoresis hybridization experiments provide the same information as obtained by isoenzyme analysis using a dozen or more enzymes. The clonal theory of T. cruzi propagation is supported by our results since the strong correlation between isoenzyme classification and molecular karyotype is difficult to explain with a sexual mode of replication. No minichromosomes were detected in any of the T. cruzi samples studied. Neither was any strong correlation found between the clinical manifestations of Chagas' disease and the molecular karyotypes of the T. cruzi isolates.

Animals↗
PubMed2005

Classification of structural images via high-dimensional image warping, robust feature extraction, and SVM.

This paper presents a method for classification of medical images, using machine learning and deformation-based morphometry. A morphological representation of the anatomy of interest is first obtained using high-dimensional template warping, from which regions that display strong correlations between morphological measurements and the classification (clinical) variable are extracted using a watershed segmentation, taking into account the regional smoothness of the correlation map which is estimated by a cross-validation strategy in order to achieve robustness to outliers. A Support Vector Machine-Recursive Feature Elimination (SVM-RFE) technique is then used to rank computed features from the extracted regions, according to their effect on the leave-one-out error bound. Finally, SVM classification is applied using the best set of features, and it is tested using leave-one-out. The results from a group of 61 brain images of female normal controls and schizophrenia patients demonstrate not only high classification accuracy (91.8%) and steep ROC curves, but also exceptional stability with respect to the number of selected features and the SVM kernel size.

Algorithms↗
PubMed1985

Limitations and problems of diabetes classification from an epidemiological point of view.

There are residual ambiguities between the two main current glycaemic definitions of the categories of DM, IGT and normal GT which should be resolved. IGT is clearly a highly heterogeneous category and could with advantage be resolved into its identifiable subsets though adequate data for this is not yet available. The concept of insulin dependency requires clearer definition for operational purposes. Biochemical parameters (e.g. C-peptide responses) may help. Attempts to combine clinical manifestations and pathogenic mechanisms in a single classification (e.g. IDDM/NIDD versus Type I/Type II) should be handled with care. If the term Type I is to be retained, it should be applied to a defined pathogenic process, not to a clinical type of DM. The term Type II is inadequately defined at present. IDDM and NIDDM, clinical descriptive terms, may be provoked by a variety of pathogenic mechanisms (i.e. they are 'heterogeneous'). They could be subclassified by mechanism (when known). More visibility should be given in classification to non-Europid forms of DM (e.g. 'Tropical or 'Nutritional' DM). A staging dimension should be recognised in classifications of DM. Future classifications will benefit from the incorporation of the presence or absence of susceptibility/resistance factors to diabetes itself or to its severe long term sequelae. There remain uncertainties about the definitions and clinical implications of gestational DM (and gestational IGT) not discussed above. It should be accepted that different user groups may need different subclassification of diabetes and glucose intolerance to meet their specific requirements and so long as this is made clear and definitions are adequate this should not be a problem. However, for the present, all groups should accept the proposed glycaemic definitions of DM or IGT for the purposes of comparability.

Adult↗