Symmetry and asymmetry analysis and its implications to computer-aided diagnosis: A review of the literature

Although clinicians have long sought to integrate computer-aided diagnostic (CAD) systems into routine clinical practice, it has proven to be extremely difficult to perform fully automated algorithmic analyses on lesions, based solely on the information contained in images. To increase the utility of computerized tools, it would be intuitive to incorporate anatomical and pathological knowledge and heuristics to help the system draw diagnostic inferences. In neuro-imaging applications, for example, one way to perform this knowledge integration is to uncover symmetry/asymmetry information from the corresponding regions of the head and to explore its implication to positive clinical findings. To correctly quantify asymmetric patterns in brain images, however, the symmetry axis, or the symmetry plane, needs to be appropriately oriented in space; i.e., the symmetry plane needs to be correctly identified either manually or using computerized methods. This review will provide an overview of the current state of knowledge of both symmetry axis/plane detection, and asymmetry quantification in neuro-images.     

Diagnostic strategy,genetic diagnosis and identification of new mutations in intermittent porphyria by denaturing gradient gel electrophoresis

Acute intermittent porphyria (AIP) is an autosomal dominant inherited disease of heme metabolism caused by mutations in the hydroxymethylbilane synthase gene. Diagnosing AIP during an acute attack using traditional biochemical markers is unproblematic, but it can be difficult to obtain a definite diagnosis in asymptomatic carriers. These limitations may, however, be solved through a genetic approach for diagnosing AIP carrier status. A mutation screening assay based on the denaturing gradient gel electrophoresis (DGGE) principle was established in a setup that allows within 24 hr to pinpoint which of the 15 exons of the hydroxymethylbilane synthase gene carries the underlying mutation, and thereby reduces subsequent sequencing, needed to determine the specific mutation, to this particular gene region. To evaluate sensitivity and specificity of the DGGE assay, samples from 22 AIP patients with known mutations and six healthy controls were examined in a blinded design. Following unblinding, it was revealed that in all 22 AIP samples the correct mutation carrying region had been pointed out. In two samples containing a previously undescribed polymorphism, this additional region was also pointed out. All controls were correctly characterized as normal in the DGGE assay. Subsequently, to evaluate the assay in the clinical setting, samples from six previously uncharacterized Danish AIP probands were examined and the underlying mutation detected in all six. In conclusion, a simple and sensitive mutation screening assay based on the DGGE principle allows genetic diagnosis of AIP in a routine setting and may be used as an additional tool in genetic counseling of AIP families. Hum Mutat 9:122–130, 1997. © 1997 Wiley-Liss, Inc.     

Specificity of allergen skin testing in predicting positive open food challenges to milk, egg and peanut in children.

BACKGROUND: The specificity of allergen skin prick testing to diagnose clinically relevant food allergy is controversial. OBJECTIVES: To determine the specificity of the allergen weal diameter to correctly identify children who react on formal open food challenges. METHODS: Over a 9-year period children referred to a tertiary allergy clinic for the evaluation of suspected food allergy were prospectively studied. Allergen skin prick testing to cow milk, egg white and peanut extracts (Dome-Hollister-Stier, Spokane, WA, USA) was undertaken using a lancet technique. All children underwent open food challenges to the relevant food(s) in a hospital clinic. Challenges were classified as positive, if objective signs were seen; negative, if the child could tolerate normal quantities of the food, daily, for one week; or inconclusive if none of the former criteria were met. RESULTS: Five hundred and fifty-five challenges were undertaken in 467 children: 339 challenges to cow milk, 121 to egg, and 95 to peanut. Fifty-five percentage of challenges were positive, 37% negative, and 8% inconclusive. For each food it was possible to identify a skin weal diameter at, and above, which negative reactions did not occur: cow milk, 8 mm; egg, 7 mm; peanut, 8 mm. In contrast, positive reactions could occur with a skin wheal diameter of 0 mm. CONCLUSIONS: In this high risk referral population it was possible to define skin weal diameters to egg, milk and peanut above which open oral food challenges were positive (100% specificity). By utilizing these measurements the need for formal food challenges can be reduced.     

Use of a rat basophil leukemia (RBL) cell-based immunological assay for allergen identification,clinical diagnosis of allergy,and identification of anti-allergy agents for use in immunotherapy

Abstract

Food allergy is an important public health problem that affects an estimated 8% of young children and 2% of adults. With an increasing interest in genetically-engineered foods, there is a growing need for development of sensitive and specific tests to evaluate potential allergenicity of foods and novel proteins as well as to determine allergic responses to ensure consumer safety. This review covers progress made in the field of development of cell models, specifically that involving a rat basophil leukemia (RBL) cell-based immunoassay, for use in allergen identification, diagnosis, and immunotherapy. The RBL assay has been extensively employed for determining biologically relevant cross-reactivities of food proteins, assessing the effect of processing on the allergenicity of food proteins, diagnosing allergic responses to whole-food products, and identifying anti-allergy food compounds. From the review of the literature, one might conclude the RBL cell-based assay is a better test system when compared to wild-type mast cell and basophil model systems for use in allergen identification, diagnosis, and analyses of potential immunotherapeutics. However, it is important to emphasize that this assay will only be able to identify those allergens to which the human has already been exposed, but will not identify a truly novel allergen, i.e. one that has never been encountered as in its preferred (humanized) configuration.     

Microfluoremetry of antigen-antibody interactions in immunofluorescence using the defined antigen substrate spheres (DASS) system. Sensitivity, specificity and variables of the method

Antigens covalently bound to spherical agarose beads were used as an artificial substrate for quantitative immunofluorescence as described previously. The defined antigen substrate spheres system (DASS system) has been further investigated in regard to important variables of the method. The influence of the density of the beads suspension, of the antigen concentration per bead volume and of the incubation time on the resulting fluorescence intensity was investigated. An immunofluorescence staining procedure standardized according to these investigations resulted in a reproducible assay. The sensitivity of the system was tested using conjugates and antisera with defined antibody content. Anti-IgG antibodies could be detected with the direct immunofluorescence technique in a concentration of 100 ng/ml and anti-ovalbumin antibodies with the indirect immunofluorescence technique in a concentration as low as 10 ng/ml. The specificity of the DASS system has also been investigated with classical methods for testing the specificity of immunofluorescence reactions, such as the neutralisation and, the blocking test. It was found that specific reactions could be completely inhibited by absorption with the appropriate antigen and significantly reduced but not completely abolished by blocking with unlabelled antiserum. The possibilities of the DASS system in fundamental and applied immunofluorescence studies are discussed.     

Evaluation of dried blood spot diagnosis using HIV1-DNA and HIV1-RNA Biocentric assays in infants in Abidjan,Côte d’Ivoire. The Pedi-Test DBS ANRS 12183 Study

This study evaluates HIV infant diagnosis on DBS using Biocentric HIV1-DNA and HIV1-RNA assays, in field conditions in Côte d’Ivoire.