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A high resolution workstation prototype for diagnosis of digital mammograms.

The development of a total digital high resolution mammography display system must meet a number of requirements that remain a challenge nowadays, most probably because of the special nature of breast imaging. In this paper, we discuss our particular approach to address some problems concerning the complexity of soft-copy diagnosis in digital mammography, such as image quality and user interface evaluation. Based on the experience obtained in the previous implementation of a medical image browser, a more ambitious project is being developed at the Department of Radiology of the University of Santiago de Compostela (Spain) in collaboration with the Department of Medical Informatics of INTELSIS, an emerging software company in our country. This new system will provide complete support to display, store and analyze mammographic studies in digital format.

Mammography↗

A novel tool for rapid prototyping and development of simple 3D medical image processing applications on PCs.

A 32-bit PC-based 3D medical image processing software package is presented. Its basic functions are the display and manipulation of medical images and the inclusion of user-written processing routines in C language. This software runs on inexpensive hardware and is easy to learn. It means the current needs of many research teams working in medical image processing.

Diagnostic Imaging↗

Mast cell degranulating (MCD) peptide: a prototypic peptide in allergy and inflammation.

The solid phase synthesis of mast degranulating peptide (MCD peptide) raised the possibility of preparing analogs and examining the pharmacology and the proposed role of this peptide as a potential agent in allergy and inflammation. MCD peptide, a cationic 22-amino acid residue peptide with two disulfide bridges, causes mast cell degranulation and histamine release at low concentrations and has anti-inflammatory activity at higher concentrations. Because of these unique immunologic properties, MCD peptide may serve as a useful tool for studying secretory mechanisms of inflammatory cells such as mast cells, basophils, and leukocytes, leading to the design of compounds with therapeutic potential.

Animals↗

Short- and intermediate-term carcinogenicity testing--a review. Part 1: the prototypes mouse skin tumour assay and rat liver focus assay.

Carcinogenicity testing is by far the most expensive and time-consuming study type of toxicology. For many years, the lifetime exposure with the maximum tolerated dose in two rodent species has been the gold standard of carcinogenicity testing of pharmaceuticals. Major change was introduced by the Fourth International Conference on Harmonization in July 1997; a chronic rodent bioassay in one species and a short-term carcinogenicity assay are regarded as sufficient for registration. Such requirements provide the opportunity to redirect the vast resources previously spent on the lifetime study in the second species. Numerous experimental protocols for short- and intermediate-term carcinogenicity testing in many target tissues have been available for years. The first part of this review describes the basic principles of short- and intermediate-term carcinogenicity testing using the examples of the widely used mouse skin tumour assay and the rat liver foci assay. In the context of these experimental models, the discrimination and quantification of initiating and promoting activity and the use of preneoplastic lesions as endpoints in carcinogenicity testing are described. The review includes the limitations of the models with regard to the extrapolation from effects observed in animal experiments to a potential exposure of humans.

Age Factors↗

Susceptibility to urethane carcinogenesis of transgenic mice carrying a human prototype c-Ha-ras gene (rasH2 mice) and its modification by butylhydroxytoluene.

The susceptibility of rasH2 mice to urethane lung carcinogenesis and the modifying effects of butylhydroxytoluene (BHT) on development of pulmonary lesions were examined. Single i.p. injections of urethane at 250 mg/kg in males or 500 mg/kg in females induced alveolar/bronchiolar adenomas within 6 weeks. At 4 weeks after the injection with a dose of 1000 mg/kg, adenomas occurred in both sexes. BHT administration increased the multiplicity of hyperplasias observed 3 weeks after the urethane injection and additionally caused adenomas which did not occur in the urethane alone-treated animals. The overall data suggest the possibility of rapid assays for lung carcinogens using rasH2 mice.

Adenoma↗

A prototype analysis of psychological situations through the lens of alcohol expectancies and gender.

The psychological situation, with significant origins in cognitive and personality psychology, consists of the meaningful environment encountered by an individual at a given time. In the present study, participants generated the characteristics (environmental, emotional, social, and cognitive) that they found as characteristic of "dating," "blind dating," and "drinking with friends" situations. Participants also completed a brief form of the Alcohol Expectancy Questionnaire (Brown, Goldman, Inn, & Anderson, 1980). Results indicate that women were more likely to characterize "drinking with friends" with negative descriptors; women were also likely to have more overlap than men in their schemas for "dating" and "drinking with friends." Participants with stronger alcohol expectancies also displayed more overlap in their schemas for "dating" and "drinking with friends" than did those with weaker expectancies. Results are discussed in terms of differing drinking experiences for men and women, and on the relationship between situational cues and expectancies.

Adult↗

Raymond Curtis: the prototypical hand surgeon.

Raymond Curtis was an unusual man who lived in unusual times and made unusual contributions. He promoted hand surgery, a specialty that was little known in his early time. He educated many surgeons in the science, art, and philosophy of hand surgery. He favorably impacted the course of the American Society for Surgery of the Hand (ASSH) by his prudence and desire to advance its cause. His influence has altered the topography and milieu of our specialty and contributed to its progress and prosperity. His legacy is perpetuated by many of his protégées who continued to emulate his humility, intensity, and unique craftsmanship.

Education, Medical↗

Psychophysics of a prototype peri-modiolar cochlear implant electrode array.

Psychophysical measurements were performed in three hearing-impaired adult subjects implanted with a CI22 cochlear prosthesis (Cochlear Ltd.) fitted with a developmental peri-modiolar electrode array. The array was manufactured with a curvature approximating that of the inner wall of the scala tympani but, after straightening and insertion, lay on average about half way between the inner and outer walls of the scala. All subjects were tested with bipolar stimulation; two were also tested with monopolar, employing the most basal electrode as the return. Maximum comfortable level and threshold reduced with decreasing distance of electrode from the modiolus, whereas dynamic range increased. The linearity of the loudness growth function did not vary significantly with electrode position but the function was more non-linear for lower maximum comfortable levels. Current level discrimination, normalized with respect to dynamic range, improved with decreasing distance of electrode from the modiolus in two subjects. Pitch varied regularly with insertion depth of the stimulated electrode for bipolar stimulation in two subjects and also for monopolar stimulation in one subject. Electrode discrimination was enhanced by closeness to the modiolus. Whereas the forward masking patterns for bipolar stimulation of electrodes close to the modiolus had a sharp double-peaked structure, those for monopolar stimulation were flatter and had a single peak.

Adult↗

Hair-MAP: a prototype automated system for forensic hair comparison and analysis.

This paper demonstrates the feasibility of the automation of forensic hair analysis and comparison task using neural network explanation systems (NNESs). Our system takes as input microscopic images of two hairs and produces a classification decision as to whether or not the hairs came from the same person. Hair images were captured using a NEXTDimension video board in a NEXTDimension color turbo computer, connected to a video camera. Image processing was done on an SGI indigo workstation. Each image is segmented into a number of pieces appropriate for classification of different features. A variety of image processing techniques are used to enhance this information. Use of wavelet analysis and the Haralick texture algorithm to pre-process data has allowed us to compress large amounts of data into smaller, yet representative data. Neural networks are then used for feature classification. Finally, statistical tests determine the degree of match between the resulting collection of hair feature vectors. An important issue in automation of any task in criminal investigations is the reliability and understandability of the resulting system. To address this concern, we have developed methods to facilitate explanation of neural network's behavior using a decision tree. The system was able to achieve a performance of 83% hair match accuracy, using 5 of the 21 morphological characteristics used by experts. This shows promise for the usefulness of a fuller scale system. While an automated system would not replace the expert, it would make the task easier by providing a means for pre-processing the large amount of data with which the expert must contend.

Algorithms↗

Identification of in vitro cytochrome P450 modulators to detect induction by prototype inducers in the mallard duckling (Anas platyrhynchos).

Seven modulators of mammalian monooxygenase activity were screened for their ability to selectively stimulate or inhibit in vitro monooxygenase activities of hepatic microsomes from mallard ducklings treated with phenobarbital, beta-naphthoflavone, 3,3',4,4',5-pentachlorobiphenyl or vehicle. Microsomes were assayed fluorometrically for four monooxygenases: benzyloxy-, ethoxy-, methoxy-, and pentoxyresorufin-O-dealkylase, in combination with each of the seven modulators. Four combinations: alpha-naphthoflavone and 2-methylbenzimidazole with benzyloxyresorufin, and Proadifen with methoxy- and ethoxyresorufin, respectively, were evaluated further. beta-Naphthoflavone-treated groups were clearly distinguished from the corn oil vehicle control group by all of the assays and by the effects of the modulators in three of the four assay/modulator combinations. Enzyme activities of the phenobarbital and saline groups were statistically similar (P > or = 0.05) when assayed without modulator added, but each assay/modulator combination distinguished between these groups. The PCB-treated group was distinguished from the corn oil vehicle control group only for BROD activity, with or without the presence of modulator. Graphing of per cent modulation of BROD activity versus initial BROD activity provided the clearest distinction between all of the study groups. Identification of these selective in vitro modulators may improve detection and measurement of low level cytochrome P450 induction in avian species. Also, both the monooxygenase activities induced and the impacts of the modulators indicated differences between mammalian and avian cytochromes P450.

Animals↗

Avian mycoplasma infections: prototype of mixed infections with mycoplasmas, bacteria and viruses.

Mixed infections involving mycoplasmas, viruses and bacteria are well recognized in chickens. Synergism has been demonstrated between Mycoplasma gallisepticum and the viruses of Newcastle disease and infectious bronchitis and Escherichia coli, although the outcome of infection is influenced by many factors associated with the host and the organisms. Airsacculitis in broilers due to M. synoviae or M. gallinarum may be precipitated by concurrent respiratory virus infections including vaccine strains. Turkeys, geese and ducks have been less well studied, but similar interactions seem to occur. Such observations may give an indication as to the likely interactions between mycoplasmas, viruses and bacteria in other host species.

Air Sacs↗

Posterior capsular opacification and intraocular lens decentration. Part II: Experimental findings on a prototype circular intraocular lens design.

In a prospective randomized study, 25 New Zealand white rabbit eyes were implanted with four intraocular lens (IOL) designs. These included a one-piece modified J-loop IOL, a three-piece modified J-loop IOL, a rigid disc IOL, and an experimental compressible disc (CD) IOL. The CD IOL revealed the lowest mean posterior capsular opacification (PCO) of all IOLs tested (P less than .01). With all lenses tested, a positive correlation between PCO and decentration was found (R = 0.55, P less than .05). These results suggest that because of its design features (i.e., one-piece construction, biconvex optic, posterior angulation of the fixation element), the CD lens produces a mechanical barrier against lens epithelial cell migration and reduces the incidence of PCO.

Animals↗

Prediction of ocular irritancy of prototype shampoo formulations by the isolated rabbit eye (IRE) test and bovine corneal opacity and permeability (BCOP) assay.

The isolated rabbit eye (IRE) test and bovine corneal opacity and permeability (BCOP) assay were evaluated for their ability to predict the eye irritation potential of a range of hair shampoo formulations, some containing a novel non-surfactant ingredient known to be an ocular irritant. The additional endpoints of corneal swelling and histological examination were incorporated into the standard BCOP protocol. Historic Draize data were available for several of the formulations and served as a reference. The standard BCOP assay (without histology) failed to distinguish between shampoos of low and high irritant potential, when exposure times of 10 and 60 min were employed (for undiluted and 10% dilution of the shampoos, respectively) and the in vitro score classified the majority of formulations as mild. The incorporation of the histological endpoint to the BCOP protocol allowed discrimination between formulations of differing irritancy, and should be included to augment the standard BCOP protocol. Corneal swelling values did not, however, correlate with the irritant potential of the shampoos tested. The IRE which includes the endpoints of corneal swelling and histopathological scoring produced classifications of irritancy that were fairly consistent with in vivo data and distinguished between the high and low irritant potential shampoos.

Animal Testing Alternatives↗

Fear responses to mock magnetic resonance imaging among college students: toward a prototype experiment.

Two hundred randomly selected student participants (139 females, 61 males) responded initially to questionnaires that quantified variables such as state and trait anxiety, anxiety sensitivity, claustrophobia, and panic/agoraphobia. Later they were informed that a mock magnetic resonance imaging (MRI) procedure was upcoming, and were prompted to provide self-efficacy ratings vis-à-vis completing the procedure. Finally, the participants' behavioral reactions to a mock MRI procedure were characterized; their heart beats were recorded and ratings of fearfulness were acquired. One purpose of the research was simply to tally numbers of participants who responded fearfully in various ways: 7 failed the procedure behaviorally, 7 others completed the procedure but did so fearfully, 17 others completed the procedure but manifested excessive heart-rate responsivity. A second purpose of the research was to "predict" subjects' fear-response categorization psychometrically and/or with self-efficacy ratings: psychometric data related to claustrophobia predicted subjects' fear-response categorization as did self-efficacy ratings. According to these results mock MRI assessment among college students provides a promising context for research on claustrophobia.

Adult↗

A prototype 3D CT extension for radiotherapy simulators.

In this paper we present a report on our custom 3D CT extension capable of producing fully 3D tomographic studies from conventional radiotherapy simulator cone-beam fluoro output. The extension consists of a common PC system on which a proprietary software toolkit provides the appropriate environment for reconstruction and acquisition of cone-beam data provided by commercial simulator fluoro video chains. The extension may compare favorably with CT options offered by simulator manufacturers: in particular, multi-slice single-scan reconstruction seems to be achievable while the current commercial solutions are based on single-slice single-scan. Radiotherapy applications include on-line treatment planning, patient treatment verification and registration.

Animals↗

Transient immunosuppressive effect induced in rabbits and mice by the human spumaretrovirus prototype HFV (human foamy virus).

Spumaviruses (foamy viruses) constitute one of the three retroviral genera isolated from man. Although spumaviruses have not been clearly linked to a given pathology in humans and other infected species, it is well established that they lead in vivo to chronic infections without detectable viral expression. We thought it of interest to investigate certain aspects of the pathology induced in laboratory animals by human foamy virus (HFV). In this work, we demonstrate that HFV infection of rabbits and mice gives rise to a transient immunosuppressive effect, as evaluated in vitro by lymphocyte transformation tests. This phenomenon occurs shortly after viral inoculation, at around 4-5 days, and regresses within thirty days.

Animals↗

Factor V: a prototype pro-cofactor for vitamin K-dependent enzyme complexes in blood clotting.

The relative abundance of factor V, factor X and prothrombin has enabled detailed analyses of the prothrombinase complex. Determination of the primary structure for factor V has provided the basis for examination of structure-function relationships. The imminent in vitro expression of recombinant factor V will provide the opportunity for site-specific mutagenesis and a verification of these structure-function relationships. A comparison of the physical properties and primary structures for factors V and VIII has revealed extensive similarities in these two cofactor proteins. This observation indicates that a direct application of the technology developed for the analysis of prothrombinase will lead to an equal understanding of the factor Xase complex. Whether similar relationships exist for other blood coagulation enzyme complexes remains to be determined.

Factor V↗