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PubMed1996

Accuracy of clinical diagnosis of cirrhosis among alcohol-abusing men.

There is a considerable variation among specialists in the use of liver biopsy for the diagnosis of alcoholic cirrhosis, which is often based solely on clinical findings, sometimes supplemented with blood tests. To assess the diagnostic accuracy that may be achieved by this approach, we related items of the history, symptoms and signs, and routine blood tests to the presence/absence of cirrhosis in a unique, previously established, consecutive series of 303 alcohol-abusing men, in whom liver biopsy was performed irrespective of the clinical and biochemical findings. Using logistic regression analyses, we created a clinical, a combined clinical and biochemical, and a pure biochemical diagnostic model. The probability of cirrhosis in patients with the specified characteristics was estimated, the diagnostic accuracy was assessed as functions of diagnostic thresholds for cirrhosis defined by the probability of cirrhosis varying between 0 and 1,and confidence intervals were estimated by bootstrap sampling. The clinical model, including facial teleangiectasia, vascular spiders, white nails, abdominal veins, fatness, and peripheral edema, could be used with high diagnostic accuracy and it was clearly superior to the biochemical model. Adding biochemical findings to the clinical model improved the accuracy of the clinical model only slightly. We conclude that cirrhosis may be diagnosed in alcohol-abusing men with a high accuracy using selected, properly weighted clinical observations only.

Adult↗

PubMed1991

Logistic discriminant analysis improves diagnostic accuracy of exercise testing for coronary artery disease in women.

BACKGROUND: Diagnostic accuracy of the exercise electrocardiogram in women has been shown to be limited for the detection of coronary artery disease. New diagnostic methods based on computer analysis of the exercise electrocardiogram and multivariate analysis have improved the diagnostic value of exercise testing in male subjects. The aim of the present study was to assess whether the diagnostic value of exercise testing can be enhanced in women by using multivariate analysis of exercise data. METHODS AND RESULTS: Between 1978 and 1984, 135 infarct-free women underwent exercise testing and coronary angiography. Significant coronary artery disease was present in 41% of the patients. In this first group, maximal exercise variables were submitted to a stepwise logistic analysis. Work load, heart rate, and ST60X were selected to build a diagnostic model. The model was tested in a second group of 115 catheterized women (significant coronary artery disease in 47%) and of 76 volunteers. We compared the present model with conventional analysis of the exercise electrocardiogram, with ST changes adjusted for heart rate, and with a previously described analysis. In both groups, sensitivity was better with the present model (66% and 70%) than by conventional (68% and 59%) and by the previously described analysis (57% and 44%) without a loss of specificity (85% and 93%). Receiver-operator characteristic curves showed also a better diagnostic accuracy with the present model. CONCLUSIONS: In women, logistic analysis of exercise variables improves the diagnostic value of exercise testing. It yields a significantly better sensitivity without a loss of specificity.

Coronary Disease↗

PubMed1981

Nosology of primary affective disorders and application to clinical research.

The nosology of primary affective disorders is discussed with specific application of a six-stage model for clinical diagnosis utilizing an integrated nosological approach. The six phases of the clinical diagnostic model include: 1) Clinical description with delineation from other syndromes. 2) Physical and neurological factors. 3) Laboratory studies including psychological testing. 4) Family studies (pedigree studies). 5) Longitudinal--natural history studies. 6) Treatment outcome studies. Utilizing this six-stage model, the specific attributes of several major diagnostic systems for the affective disorders are compared and discussed. Specific operational diagnostic criteria described by Feighner et al., the Research Diagnostic Criteria by Spitzer et al., DSM-III, and ICD-9-CM are compared, and the merits of each are discussed. The nosological breakdown of the affective disorders with emphasis on the primary versus secondary axis and the unipolar versus bipolar axis is presented. In view of the ongoing development of more specific biological management of the affective disorders, it is imperative that systematic operational diagnostic criteria be utilized in current research to enhance homogeneity of research populations and to enhance communication between research centers.

Humans↗

PubMed2004

Evidence-based medicine, medical decision analysis, and pathology.

Recent advances in molecular pathology and other technologies such as proteomics present pathologists with the challenge of integrating the new information generated with high-throughput methods with current diagnostic models based mostly on histopathology and clinicopathologic correlations. Parallel developments in the field of medical informatics and bioinformatics provide the technical and mathematical methods to approach these problems in a rational manner. However, it remains unclear whether pathologists or other medical specialists will become primarily responsible for the development and maintenance of these multivariate and multidisciplinary diagnostic and prognostic models that are hoped to provide more accurate, individualized patient-based information. Evidence-based medicine (EBM) and medical decision analysis (MDA) are relatively new disciplines that use quantitative methods to assess the value of information, differentiate fact from myth, and integrate so-called best evidence into multivariate models for the assessment of prognosis, response to therapy, selection of laboratory tests, and other complex problems that influence individual patient care. We review from an epistemological viewpoint the current approach to information in pathology and describe some of the concepts developed by the practitioners of EBM and MDA.

Computational Biology↗

PubMed1991

A note on multiple testing procedures in linkage analysis.

Controversy over the impact of multiple testing procedures in linkage analysis is reexamined in this report. Despite some recent claims to the contrary, it is shown that testing multiple markers decreases the posterior false-positive rate among significant tests, rather than increasing it; this is true whether the trait of interest is simply monogenic or complex, or even if the genetic model is misspecified. However, if the true mode of inheritance is complex, or if the genetic model is misspecified, the power to obtain a significant result when linkage is present may be reduced, while the significance level is not, leading to an inflation of the posterior false-positive rate. Furthermore, the posterior false-positive rate increases with decreasing sample size and may be unacceptably high for very small samples. By contrast, testing multiple genetic models, by varying either mode-of-inheritance parameters or diagnostic categories, does lead to an inflation of the posterior false-positive rate. A conservative correction for this case is to subtract log10t from the obtained maximum lod score, where t different genetic and/or diagnostic models have been tested.

Genetic Linkage↗

PubMed2026

Screening of molecular biomarkers ASPN and LBH and construction of a prediction nomogram for the progression of esophagogastric junction adenocarcinoma.

BACKGROUND: Esophagogastric junction adenocarcinoma (EGJA) is an aggressive malignancy of the digestive system with poor prognosis. Early diagnosis and accurate prediction of tumor progression remain major clinical challenges. This study aimed to identify and validate molecular biomarkers and construct a precise diagnostic model, providing a scientific basis for individualized treatment. METHODS: Differentially expressed genes (DEGs) associated with EGJA were identified using The Cancer Genome Atlas (TCGA) database. Quantitative real-time polymerase chain reaction (qRT-PCR) was then performed for further screening. The protein expression levels of ASPN and LBH were validated by immunohistochemistry in both tumor and adjacent non-tumor tissues. A nomogram was constructed by integrating clinical and pathological features, and its performance and clinical utility were assessed using receiver operating characteristic (ROC) curves and decision curve analysis (DCA). RESULTS: Immunohistochemistry demonstrated that the protein expression of ASPN was significantly upregulated in tumor tissues, with expression levels increasing with tumor stage. Conversely, LBH was downregulated in tumor tissues and decreased with advancing stages. The predictive model achieved an area under the curve (AUC) value of 0.977, indicating excellent diagnostic and prognostic performance. DCA confirmed the clinical net benefit of the model. CONCLUSIONS: ASPN and LBH are critical molecular biomarkers for EGJA. The nomogram combining these two markers enables accurate distinction between early and advanced-stage tumors, offering significant support for early diagnosis of EGJA.

ASPN↗

PubMed1977

[Central accounting as a model of laboratory diagnosis].

From the experiences in the field of scientific organisation of the last years results a laboratory-diagnostic model with an automatic laboratory, a district laboratory and larger central units, so-called coordination laboratories which work together with about 10 to 20 laboratories and guarantee an up-to-date diagnostic spectre for the whole territory. Apart from the increasing investigation frequency, a constant dilatation of the diagnostic spectre and improved quality control of structural conditions must be taken into consideration. The constructed model which demands the collaboration of all institutions meets these critical problems. A central balancing should also extend to the personal and technical apparative capacity. Apart from this the system is to be extended by further automation in the sense of a machine activity with improvement by control and regulation processes. An electronic data processing improves the functional capacity only when the analytic data processing has achieved a high level. The cooperation in the field of laboratory diagnostics is not only a task in scientific organisation, but in the same way also scientific problems are solved together. The requirements increasing in qualitative and quantitative respect may optimally be fulfilled only by the two partners, clinic and laboratory. With increasing independence the laboratories should in scientific and organizational respect remain a place of meeting for laboratory scientist and physician.

Clinical Laboratory Techniques↗

PubMed1996

Additional support for schizophrenia linkage on chromosomes 6 and 8: a multicenter study. Schizophrenia Linkage Collaborative Group for Chromosomes 3, 6 and 8.

In response to reported schizophrenia linkage findings on chromosomes 3, 6 and 8, fourteen research groups genotyped 14 microsatellite markers in an unbiased, collaborative (New) sample of 403-567 informative pedigrees per marker, and in the Original sample which produced each finding (the Johns Hopkins University sample of 46-52 informative pedigrees for chromosomes 3 and 8, and the Medical College of Virginia sample of 156-191 informative pedigrees for chromosome 6). Primary planned analyses (New sample) were two-point heterogeneity lod score (lod2) tests (dominant and recessive affected-only models), and multipoint affected sibling pair (ASP) analysis, with a narrow diagnostic model (DSM-IIIR schizophrenia and schizoaffective disorders). Regions with positive results were also analyzed in the Original and Combined samples. There was no evidence for linkage on chromosome 3. For chromosome 6, ASP maximum lod scores (MLS) were 2.19 (New sample, nominal p = 0.001) and 2.68 (Combined sample, p = .0004). For chromosome 8, maximum lod2 scores (tests of linkage with heterogeneity) were 2.22 (New sample, p = .0014) and 3.06 (Combined sample, p = .00018). Results are interpreted as inconclusive but suggestive of linkage in the latter two regions. We discuss possible reasons for failing to achieve a conclusive result in this large sample. Design issues and limitations of this type of collaborative study are discussed, and it is concluded that multicenter follow-up linkage studies of complex disorders can help to direct research efforts toward promising regions.

Adult↗

PubMed1997

Periodontal disease diagnosis: current status and future developments.

OBJECTIVES: This manuscript attempts to critically review traditional and currently employed methods of periodontal diagnosis, in the light of current knowledge about individual patients and sites at risk of progressive periodontal attachment loss. DATA SOURCES: Articles published over the last decade from international research journals, have demonstrated that existing methods of periodontal disease diagnosis are seriously deficient with respect to accuracy, their ability to predict ongoing or future disease activity and their ability to determine the current activity status of historically diseased sites. STUDY SELECTION: Longitudinal studies have questioned the rationale behind traditional treatment regimes and underlined the importance of site-directed therapy to avoid potentially damaging instrumentation of quiescent or healthy sites. The recent explosion in local, less invasive chemotherapies for periodontal disease management has aimed at addressing the site-specific nature of this group of diseases, but the true benefits of such novel therapies cannot be realised until more accurate and specific diagnostic techniques become available. CONCLUSIONS: The manuscript concludes that the range of clinical information collected by experienced periodontists using currently available technology is probably sufficient to manage mild-to-moderate chronic adult periodontitis. However, those patients at risk from more aggressive attachment loss, and those individuals that appear refractory to traditional therapies, require the development of more accurate diagnostic tests to compliment the revolution in site-specific therapies. A diagnostic model is presented, which attempts to draw together current and future diagnostic methods for managing the majority of periodontal disease types, and it is suggested that current diagnoses should include some assessment of "risk'.

Adult↗

PubMed1979

Non-invasive techniques in the diagnosis of jaundice--ultrasound and computer.

This study describes the use of ultrasound in 84 consecutive patients to distinguish between medical (intrahepatic) and surgical (extrahepatic) types of jaundice. Accuracy rates in the 84 patients investigated were compared with those found in 169 patients using the computer-aided diagnostic model for jaundice. In 50 patients in whom both techniques were carried out direct comparison was possible. Ultrasound failed to give adequate visualisation for technical reasons in two patients, but 75 of the remaining 82 (91.5%) were correctly separated into medical and surgical categories. A similar percentage (90%, 152 of 169 patients) were correctly classified by the computer-assisted model, and in the 50 patients assessed by both techniques correct diagnostic separation was achieved in 43 (86%) by ultrasound and in 42 (84%) by computer. However, in this latter group two of the errors with computer diagnosis were falsely positive for a surgical jaundice (extrahepatic obstruction), and a surgical exploration performed on the basis of this test could have been unnecessary. This was not found with ultrasound in these same patients, all the errors being false negative. A high degree of confidence can therefore be attached to the demonstration by ultrasound of a dilated biliary tree.

Cholestasis↗

PubMed2002

Alcohol dependence and abuse in three groups at varying familial alcoholism risk.

Three groups of young men varying in familial alcoholism risk were compared for lifetime and current Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV; American Psychiatric Association, 1994) diagnoses. A withdrawal gate diagnostic model (WGM) requiring withdrawal for a dependence diagnosis was also evaluated. Extremely high lifetime DSM-IV diagnostic rates were found for all groups (> or = 78%), with the highest rate in the highest risk group. Similar group differences obtained for individual criteria or symptoms. Although lifetime diagnostic rates were similar for the WGM and DSM-IV, virtually all cases of dependence were preceded by abuse for the WGM, unlike DSM-IV. The findings underline the importance of distinguishing degrees of familial alcoholism risk. The WGM model temporal onset findings versus DSM-IV and the high lifetime diagnostic rates obtained suggest some limitations of the DSM-IV diagnoses.

Adult↗

PubMed1994

The interaction effects of gender within the health promotion model.

A male-female stacked version of Pender's Health Promotion Model (HPM) was used to evaluate whether the causal mechanisms underlying health promotion behaviors are the same for men and women. Indicators of the conceptual variables in the HPM were obtained from the National Survey of Personal Health Practices and Consequences, 1979-1980--a telephone sample survey of 3,025 noninstitutionalized adults. All coefficients to be estimated were initially constrained to be equal for men and women, except for six direct effects originating from marital status. The estimates obtained via the LISREL VI program indicated that the stacked model did not fit the data and that additional gender interactions were required between gender and other concepts within the HPM. Based on model diagnostics and with the relaxation of some equality constraints, a modified stacked model was constructed that fit the data. The explanatory power of the model was poor, calling into question the validity of the HPM. Theorists and researchers of health promotion should not assume that the causal mechanisms underlying health promotion behaviors in men and women are identical, but must forge ahead with an exploration and clarification of possible differences.

Adult↗

PubMed1992

Linkage study of schizophrenia with markers on chromosome 11 in two Japanese pedigrees.

We examined the linkage between schizophrenia and DNA markers on chromosome 11 in two Japanese pedigrees. Thirty individuals from the two pedigrees were genotyped at the eleven polymorphisms (eight loci) studied. Data were analyzed according to three models, representing a range of single gene models from near dominant to an intermediate model. For all markers, except those at the D11S35 locus, there is no evidence for the linkage. Positive LOD scores between 1 and 1.5 are obtained for some genetic models with the polymorphism at D11S35. Two point scores for the broad diagnostic model and for the intermediate parameter set peak at 1.49.

Chromosome Mapping↗

PubMed1992

Laboratory investigation in the diagnosis of pulmonary thromboembolism.

Laboratory findings were compared with lung scans in a prospective study of 260 patients undergoing ventilation-perfusion (V/Q) lung scanning for suspected pulmonary thromboembolism. The best discrimination between different lung scan results was obtained from the level of plasma cross-linked fibrin degradation products, every patient with a scan indicating a high probability of thromboembolism having detectable levels. An acute phase response was demonstrated in patients with pulmonary thromboembolism by a raised neutrophil count and elevated levels of plasma fibrinogen and serum C-reactive protein. A normal level of serum C-reactive protein and/or plasma cross-linked fibrin degradation productions in blood taken within 4 days of onset of symptoms virtually excluded the diagnosis of pulmonary thromboembolism. Detection of free plasma DNA was not helpful in discriminating between groups with different lung scan results. Discriminant analysis was used to assess the variables examined and to derive diagnostic models. An accuracy of 78 per cent was obtained with one model for classifying test patients according to the three lung scan classes of low, intermediate and high probability. A second model, for distinguishing patients with a low and a high probability of pulmonary thromboembolism on the basis of lung scans, and a third for predicting those with a low probability on lung scan, were accurate in 94.6 per cent and 83.5 per cent of patients respectively. Discriminant models could be used in the diagnosis of pulmonary thromboembolism, especially when diagnostic imaging is not available.

C-Reactive Protein↗

PubMed1996

Genetic linkage study of bipolar disorder and the serotonin transporter.

The serotonin transporter (HTT) is an important candidate gene for the genetic transmission of bipolar disorder. It is the site of action of many antidepressants, and plays a key role in the regulation of serotonin neurotransmission. Many studies of affectively ill patients have found abnormalities in serotonin metabolism, and dysregulation of the transporter itself. The human serotonin transporter has been recently cloned and mapped to chromosome 17. We have identified a PstI RFLP at the HTT locus, and here report our examination of this polymorphism for possible linkage to bipolar disorder. Eighteen families were examined from three populations: the Old Order Amish, Iceland, and the general North American population. In addition to HTT, three other microsatellite markers were examined, which span an interval known to contain HTT. Linkage analyses were conducted under both dominant and recessive models, as well as both narrow (bipolar only) and broad (bipolar + recurrent unipolar) diagnostic models. Linkage could be excluded to HTT under all models examined. Linkage to the interval spanned by the microsatellites was similarly excluded under the dominant models. In two individual families, maximum lod scores of 1.02 and 0.84 were obtained at D17S798 and HTT, respectively. However, these data overall do not support the presence of a susceptibility locus for bipolar disorder near the serotonin transporter.

Bipolar Disorder↗

PubMedDate not supplied

The diagnostic value of scoring models for organic and non-organic gastrointestinal disease, including the irritable-bowel syndrome.

Scoring models based on history and physical examination have been developed to discriminate patients with non-organic gastrointestinal disease from those who have organic disease. The application of these models may lead to more efficient diagnosis and prevent somatization. Although the models have high diagnostic accuracy in the population in which they have been developed, their value in other populations has not been established. In this study previously developed models were tested in validation populations defined by the original selection criteria from the studies in which the models were developed and in unselected general practice and outpatient populations. The diagnostic performance of the models are expressed in terms of odds ratio and sensitivity and specificity for the classification of patients as having organic and non-organic disease. The diagnostic performance of all the models were rather low in the validation populations. Relatively few elements of the models had independent diagnostic value. In addition, the correlation between the scoring models, expressed in Cohen's kappa, was extremely low. The diagnostic values of the scoring models were not reproduced in comparable and unselected populations. Therefore, it is concluded that the diagnostic value of such a model has little external validity.

Adolescent↗

PubMed1997

[Countertransference in schizoid disorders].

Twelve experienced psychoanalysts diagnosed during a depth-psychological examination of 604 patients, coming from two different outpatient institutions, distinct clinical schizoid personality traits of 65 patients (10.7%). A further analysis researched the contribution to patient and therapist bindings and influences on the diagnosis. With the aid of a step by step regressions analysis including "solid" patient and therapist data as well as countertransference reactions of the investigator, we were able to establish an accurate diagnostical model, which enables a correct assignment with the probability of 90%. The most important diagnostic criterion proved to be the countertransference of the investigators. This demonstrates that affective processes from the therapist side-should be assessed as a potent criterion that distinctively increases the validity of the diagnosis.

Adult↗

PubMed2005

Genetic linkage analysis of the X chromosome in autism, with emphasis on the fragile X region.

The higher prevalence of autism in males than in females suggests the possible involvement of the X chromosome. To test the hypothesis that there are mutations increasing susceptibility to autism on the X chromosome, and in particular the distal portion of the long arm that encompasses the FMRI and MECP2 loci, a genetic linkage study was performed. Twenty-two fragile X-negative families multiplex for autism and related disorders were used for the study. Linkage analysis, for markers in the Xq27-q28 region, using model-free likelihood-based analysis, produced a maximum MLOD of 1.7 for the narrowest diagnostic category of the typical autism/severe autism spectrum, and nonparametric analysis produced a maximum non-parametric lod (NPL) score of 2.1 for a broad phenotype diagnostic model. Thus, this study offers modest support for a susceptibility locus for autism within the Xq27-q28 region. Further genetic investigations of this region are warranted.

Autistic Disorder↗