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A Dutch medical language processor.

This paper describes the current state of a medical language processor for Dutch. The goal is to implement a language specific front-end compatible with some existing applications that aim at the intelligent extraction and processing of information from patient discharge summaries. A complete chain for processing and understanding Dutch medical documents will be the ultimate result. The text focuses mainly on the language specific aspects of the language processing chain. Evaluation results of the already functioning components are given as well as an outline for future developments and enhancements. A short theoretical background is provided (cf. also [1-3]: Rossi Mori et al., Proc. SCAMC 90, 1990, pp. 185-189; Wingert, in: Informatics and Medicine, an advanced course, Springer-Verlag. 1977, pp. 579-646; Wingert, Proc. MEDINFO 80, 1980, pp. 1321-1331) before the description of each component in order to familiarise the non-experienced reader with the basic notions of computational linguistics.

Artificial Intelligence↗

Relationship of vascular thrombosis and inflammatory leukocyte infiltration to neointimal growth following porcine coronary artery stent placement.

BACKGROUND: Superficial and intramural thrombosis are reproducible histopathological features of the porcine coronary oversized stent injury model. Fibrin and its degradation products are chemotactic for mononuclear leukocytes, and promote the proliferation and migration of vascular smooth muscle cells (VSMC) in vitro. The goal of this study was to quantitate the serial histomorphologic evolution of thrombosis, leukocyte infiltration, VSMC proliferation and collagen accumulation following porcine coronary artery stent placement in a porcine model. METHODS: Twenty-four normocholesterolemic swine underwent oversized balloon (3.5-4.0 mm) coronary angioplasty and tantalum metal stent placement. Twenty-six different arterial sites were injured, followed by serial sacrifice at day 4 (n = 6), 8 (n = 6), 14 (n = 6), and 28 (n = 6). Quantitative analysis of the neointima was performed using a high resolution video-microscopy interface and a validated histomorphometric software program. Alpha actin-positive VSMC density (per 10(4) micro(2) neointimal area) and collagen-specific picro-sirius red fluorescence (percent of neointima) were quantitated at sites adjacent to and distant from coronary artery stent placement. RESULTS: The percent of total neointimal area occupied by resolving thrombus material was greater at days 4-8 compared to 14-28 days (59-63% vs. 1-2%; P = 0.001). Mononuclear leukocytes were also significantly increased at days 4 and 8 (92 +/- 1 and 70 +/- 8%) compared to days 14-28 (both 3 +/- 3%; P = 0.001), as a percentage of the total neointimal cellularity. Total neointimal cell density did not change (20 +/- 10, 12 +/- 6, 23 +/- 7 and 20 +/- 3 cells/10(4) micro(2); P-value, NS), despite progressive cross-sectional vascular area stenosis reduction from 7 +/- 3% at day 4 to 72 +/- 14% at day 28 (P = 0.001). Percent neointimal fibrinoid thrombus content and mononuclear leukocyte cellularity were correlated in this model (R = 0.81; P < 0.001). Peri-stent neointimal collagen staining exceeded that at vascular sites distant from porcine coronary stent placement by 14 days (29 +/- 6 vs. 15 +/- 3%), and remained greater at 28 days (35 +/- 11 vs. 16 +/- 12%) (both P < 0.05). CONCLUSIONS: Quantitative serial histomorphometry of porcine coronary vascular stent delivery sites demonstrates early (4-8 day) neointimal mononuclear leukocyte infiltration which is histomorphologically and temporally related to intramural fibrinoid thrombosis. Significant vascular stenosis and collagen deposition occurs by 14-28 days at these vascular injury sites. These data suggest a local interaction between thrombotic and inflammatory elements in porcine coronary neointima following oversized stent injury.

Angioplasty, Balloon↗

Impact on the management and delivery of primary health care by a computer-based information system.

Timely and accurate information forms the basis for management to plan and for care providers to take appropriate action. We report from a developing country a research project aimed to strengthen the information infrastructure with a computer at a Primary Health Centre. The software (MCHS) was designed to assist the care providers in the information management for the Maternal and Child Health (MCH) programme activities. In Phase I, a baseline survey was conducted to identify the needs and target groups. In Phase II, the MCHS was integrated into routine delivery of MCH to monitor the target population and help in evaluation. The research project's impact is reflected in enhanced utilization of services and quality in care, as seen by reduction of dropouts from the immunization program. In economic terms, we see that the costs for a fully immunised child are reduced with reduction of dropouts; thus, the computer system contributes to quality assurance and cost effectiveness in delivery of care.

Adolescent↗

Using the job-exposure matrix for elaborating job histories.

A first software (JHS) for the elaboration of job histories oriented toward risks was designed and results published In an article "A software for the elaboration of Job Histories". This article presents a second software (JES), based on the use of a job-exposure matrix designed for one company. The matrix is essentially a database, an organized gathering of information concerning the company. The two softwares are inter-faced and both run on a PC. When properly exploited, the two softwares can serve as an asset for epidemiological studies dealing with occupational health.

Database Management Systems↗

Computer-assisted rheological evaluation of microsamples of mucus.

Dynamic viscoelasticity measurements are required in many studies on biological fluids and they can be performed by determining the corresponding strain when a sinusoidal shear stress is applied to a sample. In several circumstances the amount of fluid that can be obtained for analysis in physiological conditions does not exceed microliters. In this context, the microrheometer technique is a useful approach to determine the dynamic rheological profile of the samples. However, the manual calculation of the desired parameters is tedious and time-consuming. This paper describes a menu-oriented program in order to facilitate its use by non-experts. The comparison between manual and computer-aided calculations demonstrated that the program reduced the time of measurement, and reduced intra- and interobserver variations. The program was developed on an IBM compatible PC in Microsoft C 5.1, and tested in a blind study to check the advantages in terms of time and reproducibility of the system verified by the concordance of two independent observers (interobserver influence) in two different occasions (intraobserver influence).

Bronchi↗

The determination of the absolute bioavailability for drug substances with long elimination half-lives (with PC-programs for the method of truncated areas).

A survey is given of the methods for the determination of the absolute bioavailability for drug substances with long elimination half-lives. All methods depend on the assumption of linear pharmacokinetics. Emphasis is laid on Urso and Aarons' regression method of truncated areas-under-the-curve (AUC) to obtain estimates of the absolute bioavailability, F, and the absorption rate constant, ka, without obeying the otherwise general rule of following blood or plasma levels for at least three times the terminal half-life. It is shown by simulation when the linear and when the logarithmic trapezoidal rule is to be used for the calculation of the AUC. Two PC-programs for the regression method of truncated areas are presented: one program (SIMF&KA.EXE) simulates, based on tentative pharmacokinetic parameters, whether a blood sampling scheme, together with the precision of the analytical assay, is adequate to obtain accurate and precise estimates of F and ka; the method is insensitive to large variations in the tentative value of the elimination half-life. The other program (ESTF&KA.EXE) provides estimates of F and ka, with standard deviations of the estimates, from empirical data.

Biological Availability↗

A scanning system for digital analysis of cineangiography films.

A system for scanning and digital analysis of cinefilms is presented and its performance is compared with entirely digital radiographic equipment. Apart from the difference between logarithmic and linear gray-scale representation, a higher noise level was found in the scanning system. When its spatial resolution was assessed visually, it was comparable to that of the digital system, although lower than when the cinefilming and scanning steps were evaluated separately. Algorithms for the correction of varying exposure and geometric ("pin-cushion") distortion are also presented. It is concluded that digital analysis after scanning of cinefilms can be a useful alternative to completely digital cineradiographic studies.

Algorithms↗

Computer quantitation of saturation impairment time as an index of oxygenation during sleep.

The measurement of oxygenation during sleep has become a standard procedure in the assessment of hypoxemia in patients with various disorders. However, an accepted method for quantitating this hypoxemia is not available. This study describes the development of computerized data acquisition and analysis programs to quantitate nocturnal hypoxemia in patients with sleep and breathing disorders. The acquisition program samples the voltage output from pulse oximeters used to measure oxyhemoglobin saturation (SpO2) and stores this on an IBM PC or compatible computer. The analysis program integrates the SpO2 over time below the patient's pretest baseline as well as the integral below 90, 80, 70, 60 and 50% saturation. We refer to each integral as Saturation Impairment Time or SIT. In order to compare these integrals between patients or between the same patient but different studies, the integral is divided by the total sleep study time. We refer to each of these integrals, corrected for sleep study time, as the SIT index. Evaluation of the SIT index in 10 consecutive patients referred for various sleep disorders revealed acquisition program detection and deletion of 48 of 57 (86%) oximeter probe artifacts (mean duration of 3 seconds for undetected artifacts). There were no significant artifacts in the analysis program calculation of the SIT index in these same patients. In conclusion, computer programs were developed to measure and quantitate oxygen saturation measured by oximeters. Preliminary results reveal an accuracy of measurement which should prove acceptable in further clinical evaluations.

Diagnosis, Computer-Assisted↗

EMSA: a SAAM service for the estimation of population parameters based on model fits to identically replicated experiments.

This paper presents a new technique for the aggregation of models to produce population parameter estimates based on a set of identically replicated experiments. After describing the theoretical basis for the technique we discuss tactical and strategic issues associated with its implementation in the SAAM software. Finally, we demonstrate its utility in the aggregation of models fitted to four simulated experiments.

Algorithms↗

Intuitive user interfaces (IUI): a CASE starting point for design and programming.

The acceptance of a software product depends to a considerable extent on the user interface. The class of graphic-oriented user interfaces that are called Intuitive User Interfaces (IUI) is described. These interfaces allow the user to learn to operate software programs quickly. In the following the graphical layout put to use in an IUI is elaborated. All images the layout consists of are created with the aid of a paint program. Using these images, a procedure for creating, programming and linking an IUI to software applications is discussed and recommendations are made concerning software and hardware demands for easily creating IUIs. Practical experience of the authors with this procedure, mainly in the medical area, is described.

Computer Graphics↗

On the assessment of bioequivalence in a two-period cross-over design.

The results obtained with Meineke and De Mey's algorithm for posterior probability distributions in the nonparametric evaluation of two-period cross-over bioequivalence studies are critically discussed. Suggestions for improvement of their program NEWPARM are given. It is shown that this program in its present form cannot handle the results from bioequivalence studies in which more than 15 subjects participated. For larger study sizes, conversion to a more powerful programming language capable of handling large three-dimensional arrays, is mandatory. An alternative algorithm, allowing large sample sizes to be analysed nonparametrically without program conversion, is offered. A general bioequivalence program written by the author, into which this alternative algorithm is implemented, has been in use by a number of pharmaceutical companies and drug regulatory agencies since February 1990; its most recent update is Version 3.7 (BIOEQV37.EXE) of October 1990.

Algorithms↗

APIS: a software for model identification, simulation and dosage regimen calculations in clinical and experimental pharmacokinetics.

APIS is a software package based on mathematical modelling which provides a reliable approach in optimizing drug therapy. It was designed to assist clinicians in interpreting blood drug levels so that drug therapy may be better and more cost-effective. It is a methodological approach to describe, predict and control the kinetic behaviour of a drug. This software incorporates the principle of Bayesian procedures, i.e. one can use all available patient information (population) to determine patient-specific parameter estimates. These estimates can then be used to design an optimal and individualized drug regimen. APIS is an attractive and useful tool for clinical and experimental pharmacokinetics. APIS may be used on any IBM compatible computer using the Microsoft-Windows environment. The software is menu driven to provide a very user-friendly tool for analysing pharmacokinetic data and for designing dosage regimens.

Amikacin↗

A microcomputer program for determining turnover rates during non-steady state conditions: application to monoamine turnover.

A program to calculate the turnover rate of monoaminergic neurotransmitters was written for use on microcomputers. The program is based on non-steady state models, i.e., measuring the rate of change of levels of neurotransmitters or their metabolites after pharmacological inhibition of synthetic or degradative enzymes. Methods have been developed to estimate monoamine turnover by measuring the rate of decrease of catecholamine levels after treatment with alpha-methyl-p-tyrosine (AMPT), a tyrosine hydroxylase inhibitor, or the increase in serotonin levels after pargyline, an inhibitor of monoamine oxidase. This program is suitable for examining either linear increases or exponential decreases in monoamine levels. The program has been tested in our laboratory for the determination of serotonin, dopamine or norepinephrine turnover after hormonal or pharmacological manipulations. The program is readily adaptable for calculation of the turnover rate of other biological molecules under non-steady state conditions.

Biogenic Monoamines↗

Preoperative assessment and prediction of postoperative results in an artificial arterial network using computer simulation.

A computer model has been developed that can be used to describe the human arterial system mathematically. It simulates the complex relationship of morphology and hydraulics in the vessel network. After entering patient data into a standard vessel model, the mean flow velocity, the flow direction, and the blood pressure at each specified point of the flow network can be calculated. The vessel picture can be altered and modified with the help of a graphic editor. Localized or diffuse stenoses, bypasses with simple or multiple anastomoses, end-to-end anastomoses, end-to-side anastomoses, etc., can be studied in terms of the hydraulic effects on the local situation or on the entire vessel system. Experimental results of ultrasonic mean flow data in vessel systems of leg and cerebral arteries of patients are compared with calculated values. The predicted and measured flow velocities show a mean difference of about 10% indicating that such a computer model may be successfully used in the optimal planning of bypass operations.

Arteries↗

Hydrophobic neighboring homology (HNH) dotplot: an approach for assessing structurally similar motifs in proteins.

Structural biology needs sensitive tools to detect homology between proteins of low sequence identity, but with closely related 3-D structures. Using a conventional dotplot method, we therefore introduced 2 concepts to improve the search for similarities between secondary structures of analyzed proteins: 'hydrophobic neighboring homology' (HNH) and 'amino acid degeneracy classes'. The amino acids are grouped into 3 subsets: hydrophobic, hydrophilic and mimetic. A 'Neighboring Similarity Index' (NSI) is calculated for every residue pair and quantifies its neighbor homology. By thresholding the homology matrix and filtering the dotplot, the homologous patterns are extracted. We have evaluated the efficiency and limits of the method using 21 protein pairs extracted from the Protein Data Bank (PDB), or selected from the recent literature. Globally, we again find the homologous structures (alpha-helices and beta-strands) of these pair proteins. The introduction of neighbor residue hydrophobicity in the conventional dotplot improves the alignment of proteins with low sequence identity (< 25%). HNH, written in standard ANSI C with the graphic library X11, under UNIX, is available on request.

Cluster Analysis↗

A method for quantitative image assessment based on redundant feature measurements and statistical reasoning.

Advances in computer graphics and electronics have contributed significantly to the increased utilization of digital imaging throughout the scientific community. Recently, as the volume of data being gathered for biomedical applications has begun to approach the human capacity for processing, emphasis has been placed on developing an automated approach to assist health scientists in assessing images. Methods that are currently used for analysis often lack sufficient sensitivity for discriminating among elements that exhibit subtle differences in feature measurements. In addition, most approaches are highly interactive. This paper presents an automated approach to segmentation and object recognition in which the spectral and spatial content of images is statistically exploited. Using this approach to assess noisy images resulted in correct classification of more than 97% of the pixels evaluated during segmentation and in recognition of geometric shapes irrespective of variations in size, orientation, and translation. The software was subsequently used to evaluate digitized stained blood smears.

Algorithms↗

A SAS macro for residual deviance of ordinal regression analysis.

In this paper, a SAS macro is described for calculating the likelihood of the 'saturated' model in the analysis of ordinal regression. The outcome variable is multinomial on an ordinal scale, while the explanatory variables can be nominal or ordinal. Several ordinal regression models may be fitted to the data. One method of testing for the goodness of fit of these regression models is by comparing the residual deviance with the chi 2 distribution. In SAS, PROC LOGISTIC may be used to fit this type of data with proportional odds model. Unfortunately, the residual deviance is not available from the output. Our SAS macro will supplement the SAS output so that the residual deviance test may be carried out. The data from an ongoing HIV study is used as an illustration.

Bias↗