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Computer-assisted monocyte esterase assay by flow-cytophotometry.

A Wang model 2200 computer has been interfaced with the Bio/Physics Systems, Inc. model 6300 Cytograf and model 2100 Distribution Analyzer. Using a custom designed software program, in conjunction with an azo-dye technic for staining monocytes for nonspecific esterase activity, it has been possible to obtain rapid and reliable data concerning relative values for intracellular monocyte esterase activity. The method is based on measuring the axial light-loss voltage signal for each of one thousand stained monocytes. Individual stained monocytes were assigned to one of four groups (A, B, C, D), dependent upon the magnitude of the signal and were given different rating values (1, 2, 3, 4) according to their group designation. A "score" was derived for each blood sample by multiplying the percentage of cells (monocytes) in each group category by the appropriate factor and summing these values. The technic permits rapid objective assessment of intracellular nonspecific esterase activity in monocytes suspended in a mixed cell population. Both Gaussian and bi-modal patterns for monocyte esterase were observed. The latter suggests a dual monocyte population.

Computers

The protein identification resource (PIR).

The Protein Identification Resource consists of an integrated computer system composed of a number of protein and nucleic acid sequence databases and software designed for the identification and analysis of protein sequences and their corresponding coding sequences. The PIR serves the scientific community through on-line access, distributing magnetic tapes, and performing off-line sequence identification services for researchers.

Amino Acid Sequence

PureMD: a Computerized Patient Record software for direct data entry by physicians using a keyboard-free pen-based portable computer.

This paper describes the data acquisition features of the PureMD Computerized Patient Record (CPR) software designed specifically for physicians. The physician uses a stylus to point, draw and handwrite on a Dynamic Dialog Interface that provides the same flexibility as the paper record and numerous other advantages. The clinical data thus entered is highly organized, easily legible and retrievable in many ways. The underlying Medical Knowledge Base (MKB) was optimized for rapid, intuitive and consistent data entry and automatic coding with minimum handwriting.

Handwriting

Implementation of surgical audit in Pakistan.

UNLABELLED: Surgical audit, while extensively practised in the West, is still widely believed an impossible attainment in developing countries owing to the high cost and technology required to implement it. It is thus a poorly understood and rarely practised exercise in these countries. In this article we attempt to demonstrate the usefulness and feasibility of implementing audit in the setting of a developing country using personal computers (PCs) with simple, inexpensive and easily available software. We discuss the results of data analysis of 18 months of audit conducted by one general surgery team (2 consultants, 4 residents) at the Aga Khan University Hospital, Karachi. OBJECTIVE: To implement surgical audit in the setting of a developing country using microcomputers with simple, inexpensive and easily available software. DESIGN: Data analysis of inpatient audit proformas filled at weekly audit meetings from January 1989-July 1990 using Dbase III Plus. SETTING: One general surgery team (2 consultants, 4 residents) in a tertiary care hospital in Karachi. MAIN OUTCOME MEASURES: Disease patterns, caseload, complication rates. RESULTS: Conditions related to the biliary system made 26.1 per cent of the admitting diagnoses; 25.3 per cent of the patients had some co-existing medical condition as well, diabetes and hypertension being most common. The overall morbidity was 12.3 per cent and the mortality 1.5 per cent. Chest infection, wound infection and urinary retention were the most common post-operative complications. CONCLUSIONS: Results of audit data analysis initiated new research projects and development of protocols to improve patient care. Audit meetings also served as teaching sessions for residents.

General Surgery

Computer assessment of life-style in a gastroenterology clinic.

To examine the potential benefit of a computer-assisted interview about life-style in gastroenterology practice, 34 consecutive patients attending a gastroenterology clinic were questioned by a computer using software designed to obtain a comprehensive history of alcohol, caffeine, cigarette, and illicit drug use, together with an assessment of exercise, sexual activity, and nutrition. Comparisons of the information obtained by the computer with clinical records revealed that physicians documented only 3% of the patients as problem drinkers, 3% as caffeine abusers, and 17% as smokers, whereas the computer identified 10% of the patients as problem drinkers, 27% as caffeine abusers, and 43% as smokers. These findings imply that patients may be more apt to tell more about adverse life-style to the computer than to a physician during clinical interview. In a sample patient population from a gastroenterology clinic, a microcomputer provides an acceptable, efficient, and potentially cost-effective way to assess life-style.

Adult

1-Mb resolution array-based comparative genomic hybridization using a BAC clone set optimized for cancer gene analysis.

Array-based comparative genomic hybridization (aCGH) is a recently developed tool for genome-wide determination of DNA copy number alterations. This technology has tremendous potential for disease-gene discovery in cancer and developmental disorders as well as numerous other applications. However, widespread utilization of a CGH has been limited by the lack of well characterized, high-resolution clone sets optimized for consistent performance in aCGH assays and specifically designed analytic software. We have assembled a set of approximately 4100 publicly available human bacterial artificial chromosome (BAC) clones evenly spaced at approximately 1-Mb resolution across the genome, which includes direct coverage of approximately 400 known cancer genes. This aCGH-optimized clone set was compiled from five existing sets, experimentally refined, and supplemented for higher resolution and enhancing mapping capabilities. This clone set is associated with a public online resource containing detailed clone mapping data, protocols for the construction and use of arrays, and a suite of analytical software tools designed specifically for aCGH analysis. These resources should greatly facilitate the use of aCGH in gene discovery.

Cell Line, Tumor

Cell migration in the rat embryonic neocortex.

Three-dimensional reconstructions of the normal rat embryonic (E) neocortex on days E15, E17, E19, and E21, using Skandha (software designed by J. Prothero, University of Washington, Seattle), show that the neocortical ventricular zone shrinks rapidly in the medial direction during cortical morphogenesis. [3H]thymidine autoradiography indicates that the shrinkage of the ventricular zone occurs before neurons in lateral and ventrolateral parts of layers IV-II are generated. Consequently, most of these neurons originate 400-1000 microns medial to their settling sites in the cortical plate. Embryos killed at daily intervals up to E21 after a single injection of [3H]thymidine on either E17 or E18 revealed the presence of a prominent migratory path, the lateral cortical stream, used by neurons migrating to the lateral and ventrolateral cortical plate; neurons migrating to the dorsal cortical plate follow a direct radial path. Arrival times of neurons in the cortical plate depend on the migratory path and are proportional to the overall distance travelled. Neurons that migrate only radially arrive in the dorsal cortical plate in two days (shortest route). Neurons that migrate laterally arrive in the lateral cortical plate in 3 days (longer route) and in the ventrolateral cortical plate in 4 days (longest route). [3H]thymidine autoradiography also shows that cells generated in the neocortical ventricular zone migrate in the lateral cortical stream for 5 or more days and accumulate in a reservoir. Cells leave the reservoir to enter the piriform cortex and destinations (as yet undetermined) in the basal telencephalon. The lateral cortical stream is found wherever the neocortical primordium surrounds the basal ganglia and is absent behind the basal ganglia. A computer analysis of nuclear orientation in anterior and posterior parts of the intermediate zone in the dorsal neocortex between days E17 and E22 shows that horizontally oriented nuclei are more common anteriorly where many cells are migrating laterally than posteriorly where most cells are migrating radially.

Animals

Trans-fissural or trans-sulcal approach versus combined stereotactic-microsurgical approach.

The combined stereotactic-microsurgical approach has been used mainly to allow the removal of small subcortical lesions, determining their location and the route to be followed. In our experience, this approach has been most useful in 5 cases of small paraventricular AVMs and another 6 small deep-seated tumoural lesions. Since the availability of MRI, we have systematically applied Yasargil's proposal to perform dissection of the cisterns or sulci to reach a lesion with minimal or no injury to normal neuroanatomy. Assisted by Computer Aided Design software, we can superimpose the MR images with those provided by conventional or digital angiography (mainly the venous phase). MRI allows us to select a route or pathway through a sulcus, and angiography helps us in locating it on the brain surface. We have applied this technique systematically during the past year, and can report 20 cases (1 AVM, 12 tumoural lesions, 1 abscess and 6 haematomas). This trans-fissural or trans-sulcal approach has allowed us resection with minimal surgical damage, after a prompt and precise location. We think that both methods are not mutually exclusive, although the trans-sulcal approach is more adequate because of less discomfort for the patient, the smaller cerebral parenchyma injury and greater anatomofunctional information for the surgeon.

Astrocytoma

An automated technique for analysis of current transitions in multilevel single-channel recordings.

Detailed kinetic studies of ion channel gating are best carried out using the patch-clamp technique which permits the measurement of the ionic current through individual channels. Typical patch-clamp recordings show the current signal, in the form of a sequence of rectangular pulses (analogous to a random telegraph signal), riding on slow baseline drift, partially obscured by high-frequency noise and distorted by filtering. In order to analyze such recordings, we have developed a set of interactive Pascal programs based on a feature-detection algorithm capable of identifying current transitions in multiple-channel recordings in the presence of substantial levels of noise and drift. Software operation is largely automated but includes provisions for examination and correction of the output. The software was optimized and systematically evaluated using simulated data with variable amounts of noise and drift. Results indicate that satisfactory performance is obtained for signal-to-noise ratio as low as four even with uncommonly large baseline drift. Steady-state processing speeds varied from 1,000 to 4,000 samples per second depending on data complexity.

Automation

Experience with gated cardiac software phantoms for quality control of applications programmes.

Ten gated cardiac software phantoms, representing normal and abnormal clinical conditions, were transferred to 9 different computer systems and tested with 11 cardiac programmes. Problems of inappropriate data format were encountered when analysing the phantoms on other systems. The global left ventricular ejection fraction (LVEF) values resulting from the different programmes were compared. Significant programme differences were found, the programmes falling generally into two groups. Few LVEF outlier values were identified. Full functional assessment of cardiac phantoms requires a set of different views which together form the phantom. Application of software phantoms for programme assessment and training requires prudence and attention to the acquired data format, frame time, and gating method for the appropriate use of phantoms.

Computer Simulation

Structured spreadsheet modeling in medical decision making and research.

The construction, evaluation, implementation, and use of models representing various algorithms, strategies, methods, theories etc. based on the analysis of great amounts of data are necessary in both Medical Research and Decision Making (MR/DM). Performing such tasks manually is not only time consuming and tedious, but also very error-prone. The appearance of a computer with its ability to store and process information has opened an opportunity to facilitate enormously and improve activities. However, the effective use of computers is limited by difficulties accompanying noncomputer specialists like doctors, nurses, and other medical staff in learning and using conventional programming languages, tools, and techniques. In this paper we present Structured Spreadsheet Modeling as a possible solution, and show that it is applicable in the MR/DM field on a concrete basis.

Adolescent

Development and validation of an automated method of the Selvester QRS scoring system for myocardial infarct size.

The Selvester QRS score for estimation of myocardial infarct (MI) size from the standard 12-lead electrocardiogram (ECG) has not yet achieved wide recognition as a valuable tool in the routine assessment of the MI patient, primarily because of the practical limitations inherent to manual application. This study examined the ECGs of 438 patients (105 normal subjects, 161 with "possible" MI and 172 with "definite" MI based on data from cardiac catheterization) to develop software for an automated method of the Selvester system in attempts to overcome the manual constraints. After a comprehensive validation process involving extensive interactions between the manual scorer and the software developer, an automated method of the Selvester system was generated that had a high correlation with manual application (r = 0.94) and was superior regarding time, training, reader bias, reproducibility and precision of measurement. These results indicate that an automated version of the Selvester QRS scoring system would resolve many of the limitations of manual application and would provide a reliable, technically accurate estimate of MI size that could be incorporated into ECG diagnostic programs and used in standard digital ECG machines.

Cardiac Catheterization

A microcomputer system for on-line collection of blood flow and related physiological data.

A multi-disciplinary approach is described for the development of a microcomputer based on-line data collection system for blood flow experiments. Well designed software provides a flexible approach to data collection, which is particularly suited to blood flow research laboratories. The choice of well supported hardware ensures ease of development with minimum time and cost.

Blood Circulation

The Gemini conundrum--a problem of unpairable data: statistical comparison of ratios each derived from two separately estimated parameters.

In biological studies it may be necessary to compare ratios of two separately estimated parameters under test and control conditions. Since it is not always possible technically to obtain paired data for the two parameters, how does one take account of their variances? By extending previously described approximations in a modified t-test we present a BASIC computer program which may be used to solve this problem.

Algorithms

Computer aided design and evaluation of limiting and serial dilution experiments.

Two computer programs are presented which can be used for the determination of the design and the statistical evaluation of data in the context of limiting and serial dilution analysis. The first program (DESIGN) gives the experimenter the opportunity to set up different designs, to improve a design according to several suggestions, to make a picture of a design and to evaluate the results of artificial data, obtained from a random experiment corresponding with the chosen design, until (s)he is convinced of having a suitable design for a particular experiment. The second program (EVALUATE) evaluates the experimental data. The design method and the statistical methods used in the programs have been chosen on practical and theoretical grounds.

Colony Count, Microbial

A personal computer-based arrhythmia generator based on mathematical models of cardiac arrhythmia.

A personal computer-based arrhythmia generator has been developed based upon mathematical models of modulated parasystole and the related equations. A system of nonlinear difference equations is used to generate the time series of RR intervals of ECG that contain normal as well as ectopic QRS waves. The ECG waveform is synthesized according to the computed RR interval and the type of QRS wave and output via DA converter in a real-time base. Various types of ECGs with ventricular ectopic beats and those with very long periods were generated by selecting values for a small number of model parameters. This method requires neither large RAM nor external memory for storing a library of arrhythmic ECGs. The theory, hardware design, software implementation on a personal computer, and experimental reconstruction of clinical ECGs based on the model are discussed.

Arrhythmias, Cardiac

The evaluation of quantitative autoradiogram processing systems for cerebrovascular research.

The development of an image processing system for quantitative autoradiography (QAR) is described, with emphasis on the evaluation of image digitization systems independent of hardware or software design. Each step of converting the autoradiographic image to a functional image of a physiological variable such as local cerebral blood flow (LCBF) or local cerebral glucose utilization rate (LCGU) is evaluated. The autoradiograms are digitized, aligned, transformed to a tissue tracer concentrations image based on the gray value (GV) of calibrated 14C standards, subtracted from each other as required in double tracer QAR, and converted to an LCBF or LCGU image using the proper tracer kinetic model. Geometric size, mean and standard deviation of the LCBF, LCGU, and tracer concentration can be measured in regions of interest. These steps are evaluated separately for their contribution to the accuracy and precision of the final, functional image. The qualities important in the final image are spatial resolution, intensity linearity, and intensity sensitivity, as well as the noise level. Techniques for evaluating the LCBF image include: (1) optimization of the input linearity and dynamic range of the video camera to maximize relative intensity sensitivity of the final functional image; (2) visual inspection of the curves used to fit various functions that are important in the conversion of the GV image to an image of physiological interest; (3) consideration of the noise introduced by the input devices and during the image conversion; and (4) above all, the integration of the various parts of the system to produce an accurate image useful in cerebrovascular research.

Autoradiography

An object-based architecture for biomedical expert database systems.

Objects play a major role in both database and artificial intelligence research. In this paper, we present a novel architecture for expert database systems that introduces an object-based interface between relational databases and expert systems. We exploit a semantic model of the database structure to map relations automatically into object templates, where each template can be a complex combination of join and projection operations. Moreover, we arrange the templates into object networks that represent different views of the same database. Separate processes instantiate those templates using data from the base relations, cache the resulting instances in main memory, navigate through a given network's objects, and update the database according to changes made at the object layer. In the context of an immunologic-research application, we demonstrate the capabilities of a prototype implementation of the architecture. The resulting model provides enhanced tools for database structuring and manipulation. In addition, this architecture supports efficient bidirectional communication between database and expert systems through the shared object layer.

Database Management Systems