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A microcomputer program for tobramycin consult services, based on the two-compartment pharmacokinetic model.

A microcomputer program has been developed to provide assistance to tobramycin clinical pharmacokinetic consult services. Written for the Apple II Plus computer with 64 K memory, one-disk drive, and a dot matrix graphics printer, this software is user-oriented and simple to operate. The program disk contains complete documentation and referenced instructions. Major sections provide empiric dosing recommendations based on population data and allow determination of dosage from measured serum concentrations. The program keeps a record of previous regimens, allows for the entry of the user's own recommendation, and provides complete flexibility for up to 15 dosage and interval changes. In addition to its dosing information and file management capabilities, the program simulates serum concentration profiles based on user-selected one-compartment, two-compartment, or two-compartment prenephrotoxic models. The program prints a consult sheet with concentration vs. time simulation, patient demographic data, and user-entered recommendations and comments. The program provides extensive disk storage capabilities for patient files, with immediate access to facilitate updating and dosing regimen changes as they occur. In addition to providing improvements in empiric dosing capabilities, pharmacokinetic modeling, and data handling, this computer software has been designed to incorporate pharmacokinetic data derived from important subpopulations into the empiric dosing algorithms. This unique aspect enables the program to provide improved empiric dosing regimens for patients who do not fall under the guidelines for any of the conventional aminoglycoside dosing nomograms.

Aging↗

A simple microcomputer-based system for real-time analysis of cell behaviour.

An image analysis package based on a BBC microcomputer has been developed, which can simultaneously track many moving cells in vitro. Cells (rabbit neutrophil leucocytes, BHK C13 fibroblasts, or PC12 phaeochromocytoma cells) are viewed under phase optics with a monochrome TV camera, and the signal digitized. Successive frames are acquired by the computer as a 640 X 256 pixel array. Under controlled lighting conditions, cells can readily be isolated from the background by binary filtering. In real-time tracking, the positions of a given cell in successive frames are obtained by searching the area around the cell's centroid in the previous frame. A simple box-search algorithm is described, which proves highly successful at low cell densities. The resilience of different search algorithms to various exceptional conditions (such as collisions) is discussed. The success of this system in real-time tracking is largely dependent upon the leisurely speed of movement of cells, and on obtaining a clean, high quality optical image to analyse. The limitations of this technique for different cell types, and the possible configurations of more sophisticated hardware, are outlined. This system provides a versatile and automated solution to the problem of studying the movement of tissue cells.

Algorithms↗

A microcomputer-based respiratory heat exchange facility for use in the diagnosis of thermally induced asthma.

Exercise-induced asthma is prevalent in many asthmatics and during the winter months can be exacerbated by cold air inhalation. A laboratory facility was required to permit early diagnosis of cold air sensitivity in these patients. This paper describes the development of a modular air conditioning system to produce a range of inhalative thermal burdens and the microcomputer interfacing to measure the rate of airway heat loss imposed. A single-stage refrigerator was built capable of cooling 150 l/min air to -25 degrees C. This was also used to generate dry ambient temperature air by rewarming the chilled air supply. An air humidifier was developed based upon natural convection and evaporation. It was capable of raising 150 l/min ambient air to 37 degrees C, 100 per cent relative humidity. In two pilot studies of 18 asthmatics it was found that the rate of respiratory heat exchange could be correlated with the magnitude of post exertional bronchoconstriction (lung dysfunction) and that exercise-induced asthma could be minimized by attenuating the rate of airway heat loss.

Adult↗

PEDA: a microcomputer program for parameter estimation and dosage adjustment in clinical practice.

PEDA, an integrated program in BASIC for implementation on microcomputers, has been developed for use in clinical practice to assist dosage adjustment for individual patients. A parameter optimization for individual patients is based on the principle of Bayes' theory and Maximum Likelihood Estimation, and utilizes a prior information on the distribution of population pharmacokinetic parameters, means and variances, as well as serum drug concentrations. The program can accommodate a one-compartment open linear model and a non-linear model at steady state (Michaelis-Menten model) and handle both uniform and non-uniform multiple dosage regimens mostly arising from clinical settings. Clinical examples which demonstrate the ability and the flexibility of the program are provided. The program may also be used as an aid for instruction in clinical pharmacokinetics.

Adult↗

A pharmacokinetic analysis program (multi) for microcomputer.

A nonlinear least squares program (MULTI) for microcomputers was developed. The program is written in BASIC programming language. Four algorithms, (1) Gauss-Newton method, (2) damping Gauss-Newton method, (3) modified Marquardt method and (4) simplex method, can be used for nonlinear curve fitting in MULTI. Up to five pharmacokinetic equations, which are voluntarily defined by the user, are simultaneously fitted to observed time courses. The executions of MULTI are demonstrated for time courses of ampicillin and oxacillin in man.

Ampicillin↗

Use of PKM-MULTI program for fitting discontinuous absorption profiles using a microcomputer.

The programs for the pharmacokinetic models with discontinuous absorption, written in BASIC, were connected to MULTI, which had been proposed for nonlinear least squares for a microcomputer by Yamaoka et al. Using this program (designated as PKM-MULTI), the same data sets previously calculated by HFCM, FITSI2 and NONLIN were fitted and the finally obtained estimates were in close agreement with those obtained previously. The plasma data of nalidixic acid were also fitted to the pharmacokinetic model with discontinuous absorption, which were suggested to be more valid compared with one compartment model with continuous absorption.

Biological Availability↗

A nonlinear multiple regression program, MULTI2 (BAYES), based on Bayesian algorithm for microcomputers.

A nonlinear multiple regression analysis program MULTI2(BAYES) was developed for microcomputers. The Bayesian algorithm which is incorporated in MULTI2 (BAYES) combines the insufficient individual patient data (individual data) with the pharmacokinetic parameters published in literatures (population parameters) to predict the plasma time course of the patient. The program is written in the minimum Microsoft BASIC commands alone to be executable on many personal computers without any modification. The numbers of parameters to estimate, independent variables and dependent variables are not restricted in use of MULTI2(BAYES). The pharmacokinetic models are defined as one pleases by the user. The four nonlinear least squares algorithms, i.e. Gauss-Newton method, damping Gauss-Newton method, modified Marquardt method by Fletcher and simplex method can be selected at user's option. MULTI2(BAYES) calculates the confidence limits of time courses at 95% significant level.

Computers↗

A nonlinear least squares program, MULTI(FILT), based on fast inverse Laplace transform for microcomputers.

A nonlinear curve fitting program MULTI(FILT) into which the fast inverse Laplace transform (FILT) is incorporated was developed on a microcomputer. FILT is an algorithm for the numerical inversion of Laplace-transformed equations (image equations) to generate the corresponding real time courses. The pharmacokinetic models can be defined in the form of Laplace-transformed equations as a subroutine in MULTI(FILT). MULTI(FILT) achieves the numerical inversion of the defined image equations according to FILT and the subsequent curve-fitting of the inverse-transformed time courses to the experimental data points to estimate the pharmacokinetic parameters by the nonlinear least-squares method. MULTI(FILT) has a function to impose constraints on the pharmacokinetic parameters. In order to verify the reliability of MULTI(FILT), the pharmacokinetic parameters estimated by MULTI(FILT) were compared with those by MULTI using 100 time courses which were artificially generated according to the Monte Carlo method, based on data for theophylline and bishydroxycoumarin. The estimated pharmacokinetic parameters by MULTI(FILT) agreed with those by MULTI. Thus, it is suggested that FILT, developed in the field of electronic technology, is also useful in the pharmacokinetic field.

Mathematics↗

A microcomputer system for prescription, calculation, verification and recording of radiotherapy treatments.

The design of a microcomputer system for the reduction of mistakes in radiotherapy is described. The system covers prescription entry, prescription and treatment calculations, and verification and recording of the treatment set-up. A telecobalt unit was interfaced to the system and in the first 12 months 400 patients have been prescribed and 5000 treatment fields verified. The prescription is entered by the medical officer using an interactive program and this prescription provides the reference for verifying the treatment set-up. The program allows amendments to the prescription to be made easily during the treatment course. The treatment parameters verified are field size, wedge and treatment time. The system uses bar-codes for patient and field identification. A reduction in the number of mistakes has been achieved and future developments are discussed.

Computers↗

Use of a microcomputer to store information on radiology cases.

A microcomputer program for storage of qualitative patient data has been applied to CT and special procedures case data. Different vocabularies have been established and utilised for these two case categories. Experience over two years involving more than 10,000 cases is discussed. Utility for statistical, research, and patient care purposes is demonstrated.

Computers↗

Morphological study of the femur in osteopetrotic (op/op) mice using microcomputed tomography.

Osteopetrosis is an inherited metabolic disorder in which normal bone remodelling is inhibited. Its primary cause is considered to be disruption of the functional balance between osteoblasts and osteoclasts as well as a reduction in the quantity of osteoclasts. The purpose of this study was to observe morphological characteristics of the femur in osteopetrotic (op/op) mice, in which the pathogenic mechanism of osteopetrosis has been shown to operate, using microcomputed tomography (micro-CT), in addition to macro-anatomical observations. Previously, micro-CT has been used mainly for morphometry of a small portion of cancellous bone. However, with recent improvements it has become possible for three-dimensional (3D) observations of bone using slightly larger samples to be made. In this study, the accuracy of reconstructed 3D images of the femur produced by micro-CT was confirmed by comparison with the original femur. In addition, an arbitrary cross-section could be displayed on the screen for detailed examination of its internal structure, and the volume percentage of trabecular bone in a particular region of interest could be measured in three dimensions. The results of this study revealed that the femur was smaller and malformed in the op/op mouse compared with the controls, and the differences were greater at the age of 18 weeks than at 5 weeks. In the control mice, bone marrow occupied a large space in the centre of the body of the femur, whereas this area was occupied by calcified bone tissue in the mutant mice. Moreover, when 3D bone density was measured in the region of interest, the value was greater in the mutants than in the controls at both 5 weeks and 18 weeks of age. This study also showed that micro-CT can be applied to 3D morphometric analyses.

Animals↗

Interlibrary loan management with microcomputers: a descriptive comparison of software.

The use of microcomputers to manage interlibrary loan processing and record keeping is examined. Once the decision is made to automate, criteria for product evaluation needs to be established. Various software options are discussed which range from using dedicated interlibrary loan management software to the development of database management programs which require original template design. Descriptive profiles and sample input screens of a number of software packages are presented.

Decision Making↗

Microcomputers in enzymology. A versatile BASIC computer program for analyzing kinetic data.

Direct curve-fitting is uncontested as the method of choice for evaluating kinetic experiments. If carried out by computer, the numerical solution of such problems is superior to customary graphical procedures in any respect. However, most programs available to date, cannot be executed by small systems. We now describe a BASIC program for desk-top microcomputers that performs linear and non-linear regression analysis of kinetic data. It may be directly applied to a number of problems common in enzyme kinetics, and is easily modified to handle further ones. The performance of the program is illustrated by some typical applications; in addition, fundamental statistical methods are discussed that allow a critical examination of the results obtained.

Aminopeptidases↗

Assessment of local area network based on the microcomputer system for data processing of perinatal medical information.

In order to control perinatal medical information, we developed a microcomputer-based local area network. This system has been in practical operation since June, 1986. We have assessed this system with regard to both patient-machine and doctor-machine interfaces. Consequently, although input operation took 20-30% longer per individual patient than before, it was more feasible for medical staff to access and retrieve the data in a real-time manner. When tested in a ten month period, this system was found to be a prototype applicable for further extending the management of the entire scope of perinatal medical information.

Computer Systems↗

The relationship between ambulatory blood pressure and physical activity in young and older shiftworkers. A quantitative assessment of physical activity using a microcomputer with acceleration sensor.

We studied the relationship between physical activity and ambulatory blood pressure (BP) in young and older shiftworkers by simultaneous recordings of activity, blood pressure and pulse rate (PR). Activity was assessed using Activetracer, a self-contained microcomputer with an acceleration sensor, attached to a waist belt. Ambulatory BP was monitored every 30 minutes for 48 hours with a TM2421. Three types of hemodynamic responses were noted in relation to the physical activity. The balance type, in which both BP and PR increase with physical activity, was observed in 5 of 10 young cases (50%) but only in 1 of 7 older cases (14.3%). The BP response type, in which the BP increases with no change in the PR, was observed in 6 of the 7 older (86%) but only in 3 cases in the young group (30%). The PR response type, in which only the PR increase correlated with activity, was observed in 2 cases in the young group (20%) and none in the older group. The difference in systolic BP between periods of activity and rest in the older shiftworker was significantly larger than that in the young group (15.9 +/- 6.4 vs. 5.9 +/- 6.6 mmHg, p < .01), although no significant difference was observed in diastolic BP. In contrast, the increase in pulse rate after movement was significantly higher in the young group (4.4 +/- 4.0 vs. 9.0 +/- 4.8 bpm, p < .05). Thus, the fluctuation of the systolic BP was more dependent on physical activity in the older group, whereas PR variations correlated with the physical activity in the young group.

Acceleration↗

A microcomputer-based vital records data base with interactive graphic assessment for states and localities.

Vital records data bases describe large populations over long periods of time, yet their organization and size often preclude or discourage their use. We constructed a microcomputer-based data base of all singleton births in Massachusetts, 1975-84. The original data were stored in 700,000 records, each 174 bytes long, occupying a total of over 120 megabytes (MB). By removing redundant information and unique identifiers, and packing the data, we store 21 fields of this information in a 16-byte record resulting in a data base of 11.1 MB, a saving of over 90 percent of disk space. By using programs written expressly for this data base, we can display a birth weight frequency plot of the entire data set in under 65 seconds on an IBM-compatible PC-AT. Comparable assessments in SAS-PC took over 105 minutes and in main frame SAS on an AS-9000 took over 37 CPU seconds. Implementing similar systems for state registries on births, deaths, cancers, and birth defects potentially offers investigators easy access to vast stores of information and would enable public health officials to produce timely reports, initiate a variety of surveillance activities, and respond rapidly to residents' inquiries about clusters and anomalous disease patterns.

Birth Certificates↗

Drug dosage in end-stage renal disease (ESRD) patients undergoing haemodialysis. A predictive study based on a microcomputer program.

Drug dosage in end-stage renal disease (ESRD) patients undergoing haemodialysis is a very complex problem because of numerous variables relating to the patient, the type of drug administered and the type of dialysis and dialyser. We carried out a multifactorial study of these parameters using a microcomputer program written in BASIC. Three sets of data were fed into the computer: those relating to the biophysical characteristics of the patient, the type of dialysis and dialyser to be used, and others relating to the chemical and pharmacokinetic characteristics of the drug. From these, a predictive intravenous dosage regimen (bolus and infusion) was compiled for each ESRD patient. To check the program we used 2 drugs (tobramycin and vancomycin) and several types of dialyser. The findings were that, with tobramycin, an ESRD patient should be given different postdialytic doses, depending on the type of dialyser used. The maintenance doses calculated by the program were similar to those usually administered to patients receiving clinical treatment with this drug. In the case of vancomycin, the program calculated the clearance value in vivo through the 'Hemoflow F60' dialyser with a polysulphone membrane. The computer program calculated the maintenance dosage of vancomycin that should be given after each dialysis cycle so that its concentration did not fall below its minimum therapeutic concentration.

Drug Therapy, Computer-Assisted↗

Microcomputer-assisted relaxation.

The present pilot study was designed to test the effectiveness of a microcomputer program developed by the authors to induce relaxation and focused attention, which are common to most clinical stress-reduction and hypnotic procedures. A nonclinical sample of 20 adults used the program on an APPLE IIc computer in two 30-min. sessions in a within-subjects design. Repeated measures analyses of variance showed significant decreases in the Spielberger State Anxiety Scale and on a visual analog anxiety scale. Limitations and implications of the study are discussed.

Adolescent↗