Problem-solving in the pre-clinical curriculum: the uses of computer simulations.
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Computer modelling technique is proposed to assist in physiological research on invertebrate neuronal membranes. The firing mechanism of a single patch of invertebrate neuronal membrane has been studied in dependence on maximum Ca++ conductance. The calculations are based on modification of Hodgkin-Huxley's data completed by a straight line approximation between experimental points of the kinetic parameters of Ca++ current and early transient potassium current. The time course of conductance changes is assumed to be proportional to m2h for Ca++ current. Three distinct potassium currents are involved into the model, viz. transient potassium current, delayed potassium current and Ca++-dependent potassium current. The modified Euler method run on a digital computer has been used for numerical integration of kinetic equations. Significant effects of Ca++ conductance on spike broadening, plateau development and spike afterhyperpolarization are represented. In the range of small Ca++ conductance an infinite spontaneous activity can be triggered by a short (suprathreshold) current pulse which may be considered a model of pacemaker activity. Plateau development resulting from potassium blocking or decreasing potassium equilibrium is facilitated by Ca++ conductance in the range of greater Ca++ conductance. The effects of voltage sensitivity of the coupling coefficient describing the current of Ca++-dependent K+ channels were studied and compared to the voltage independent case. The coupling coefficient seems to be a crucial factor in broadening the range of Ca++ conductance responsible for pacemaker activity. For greater values of Ca++ conductance, a decrease of the coupling coefficient leads to a transition from prolonged bursting to interruption of burst activity by burst-afterhyperpolarization. The blocking effect of 4-aminopyridine on fast outward current has been studied by the model which has a practical significance considering that aminopyridine is known as a convulsive agent. We suppose that it is reasonable to study the convulsive effects of aminopyridine by the model based on the kinetics of the isolated neuronal membrane. The model may help in understanding the ionic background underlying abnormal network activity during epileptic discharges of mammalian neurones.
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The advent of cheap and powerful microcomputers provides opportunities for improving the teaching of statistics in medicine. This paper describes a practical exercise in which students study the concept of statistical significance using a simple computer program which simulates a clinical trial. The students are required to make decisions about patients with incomplete data and form contingency tables for analysis. This includes analysing contingency tables with several cells having small expected frequencies. The results from 25 groups of students are collected together and presented to the class. Two null hypotheses are tested, one of which is true. For the true null hypothesis the group is likely to produce, by chance, at least one significant result at the 0.05 level. For the false null hypothesis only a minority of results will be significant, because the sample size is small. This leads to a discussion of the concept of statistical significance. The simulation model is described and the advantages and potential of this type of teaching are discussed.
BACKGROUND: The purpose of this study was to determine, whether a modified fan-shaped biopsy (MFSB) technique which utilizes six laterally directed biopsies would lead to higher detection rates of clinically threatening prostatic carcinoma than the six random systematic core biopsy (SRSCB) method. METHODS: We reconstructed 3-dimensional solid computer models of 86 autopsy prostates and 40 radical prostatatectomy specimens. Simulations of SRSCB and MFSB were then performed using the same biopsy sites except that the biopsy probe was rotated 45 degrees toward posterolateral peripheral zone for MFSB. When the Gleason sum was less than 7, clinically threatening cancers were defined as having a tumor volume > or =0.25 cc or > or =0.5 cc. RESULTS: When the cut off volume was 0.25 cc, MFSB detected significantly more threatening carcinomas in autopsy prostates than did SRSCB (P < 0.0082). This was also true for the surgical prostates (P < 0.0047) as well as for a sub-group of non-palpable carcinomas (P < 0.0047). When the cut off volume was increased to 0.5 cc, MFSB detected significantly more threatening carcinomas in the radical series (P < 0.0047) and for the non-palpable carcinomas (P < 0.0082), but not in the autopsy series. CONCLUSIONS: The MFSB technique, which utilizes laterally directed biopsies, appears to be an effective approach to improve the detection of clinically threatening prostatic carcinoma.
OBJECTIVES: Six random systematic core biopsies (SRSCB) of the prostate (biopsies from apex, middle, and base of each lobe) have been commonly used in detection of prostate carcinoma. The objective of this study was to verify the validity of the SRSCB technique in detecting cancer in prostates with low-volume tumor (less than 6 cc). METHODS: We developed a computer model of the prostate to simulate the SRSCB technique. The data for development of this model were taken from 159 radical prostatectomy specimens in which 112 patients had tumor volumes measured and in which 91 prostates had tumors with volumes less than 6 cc (by whole-mount sectioning). RESULTS: The simulation shows that only 20.3% of the simulated prostates, with total aggregate tumor volume between 0.034 and 5.1 cc, had a tumor distribution for which the SRSCB technique has a 95% probability of detecting the tumor. In fact, 26.8% had a tumor distribution that was completely disjointed from the six recommended biopsy regions. To compare these results with other possible occurrence, various biases for the angle of biopsy and the distribution of cancer foci were incorporated into the model. Study results should be viewed with the understanding that any simulated model has its limitations. In our simulated model, the shape of the simulated tumor foci (spherical) does not represent all the possible shapes of prostate cancer. However, these results indicate that detection of cancer with biopsies taken from the apex, middle, and base of each lobe of a prostate with tumor volumes of less than 6 cc may not be as effective as it is in prostates with larger tumor volumes or patients with an abnormal digital rectal examination. The study of bias models suggests that the distributional pattern of cancerous foci can have a significant impact on the effectiveness of a given biopsy strategy. CONCLUSIONS: We concluded that future attempts to improve systematic biopsy strategies for detection of low-volume cancer should include biomechanical characteristics of prostate cancer, including gland volume and tumor distribution. Driven by the conclusions from this idealized model, we have developed a three-dimensional model of the prostate gland from its whole-mount histologic maps. It is anticipated that this continuing investigation will lead to realistic guidelines for improving biopsy techniques.
Molecular dynamics using CHARMM and GEMM programs with the Star Technologies ST 100 array processor functioning at the speed of super computers was used as a searching algorithm for conformational exploration of the octapeptide Gly-Asn-Thr-Ile-Val-Ala-Glu. This poorly soluble octapeptide is the N-terminal epitope of an 11 KD glycoprotein antigen residing on human ductal carcinoma (breast) cells. Very long (nanoseconds) simulations were required. Both an alpha-helix and the N-acetyl-N1-methylamide derived minimized starting structures gave the same lowest potential energy conformation with simulations at 600 K. The same conformation was found only when using the latter starting conformation with simulations at 300 K. The lowest potential energy conformation was stabilized by 4 hydrophobic contacts and 13 H bonds completing one turn of a left-handed helix.
Outside-out patches excised from extrajunctional membrane of locust muscle were subjected to "concentration jumps" of L-glutamate, using the liquid filament switch technique, to study channel opening and closing rates, desensitization onset, and recovery from desensitization of a quisqualate-sensitive glutamate receptor (qGluR). Based on data obtained from these experimental studies, computer modeling techniques have been used in an attempt to simulate the behavior of qGluR during a concentration jump of L-glutamate. A linear model with three closed states (one unliganded, one monoliganded, and one biliganded), one open state (binding two molecules of L-glutamate), and two desensitization states (the one monoliganded, the other biliganded) leading from the unliganded closed state simulated all of the experimentally observed behavior. The results are discussed in the context of previous equilibrium studies in which desensitization was inhibited with concanavalin A and for which a ten-state model was required to simulate the behavior of qGluR.
The quantitative evaluation of pathogen transmission in the medical intensive care unit (MICU) is difficult given the small number of patients and the complexity and severity of illness. We sought to evaluate the suitability of a probabilistic computer model of our MICU, with which we could rapidly simulate infection control measures and other clinical interventions that would be impossible to perform in the real clinical setting
Accurate knowledge of tissue temperature is necessary for effective delivery of clinical hyperthermia in the treatment of malignant tumours. This report compares computer-predicted versus measured intratumoral temperatures in 11 human subjects with intracranial tumours, treated with a conceptually simple 'conductive' interstitial hyperthermia system. Interstitial hyperthermia was achieved by the use of parallel arrays of implanted, electrically heated catheters. The tissue was warmed by thermal conduction and blood convection. Simulation of intratumoral temperatures was achieved by solving a modified bioheat transfer equation on a digital computer using a finite difference method. Comparison of intratumoral temperatures from simulations and measured values differed by about +/- 0.75 degrees C. Further analysis of computed temperature distributions between catheters revealed a rapidly computable relationship between the local minimum tumour temperature and nearby catheter power and temperature that accounts for effects of varying blood flow. These findings suggest that 'on-line' prediction and control of local minimum tumour temperatures are feasible with the conductive interstitial technique.
Cost-benefit management trends in Taiwan healthcare settings have led nurses to perform more invasive skills, such as Port-A cath administration of medications. Accordingly, nurses must be well-prepared prior to teaching by the mentor and supervision method. The purpose of the current study was to develop a computer-assisted protocol using virtual reality (VR) in performing Port-A cath as a training program for novice nurses. A pre-tested and post-tested control group experimental design was used in this study. Seventy-seven novice nurses were invited from one large medical center hospital in North Taiwan. Thirty-seven and forty nurses were randomly assigned to experimental and control groups. First, we designed a 40 minute port-A cath injection VR simulation. Then, the experimental group practiced this simulation two times over 3 weeks. The control group attended the traditional class. The post-test 1 was right after completion of the simulation practice. The post-test 2 was after the second simulation practice in 3 weeks. The results showed that most novice nurses lacked Port-A cath experience both in the classroom and during the period of their practice training. The knowledge score regarding the Port-A cath technique was significantly higher in the nurses that participated in the simulation training than in the control group. The novice nurses were most satisfied with the reduction in their fear of performing the Port-A cath technique and their enhanced clinical skills. VR simulation significantly reduced error rates and increased correct equipment selection, showing that nurses who participated in the simulation may be better prepared for inserting Port-A cath.
For young patients who have early signs of coxarthrosis resulting from acetabular dysplasia, periacetabular osteotomies for correcting abnormal stress distribution can be useful for preventing the progression of the disease. However, it is difficult to confirm the optimal transposition of the osteotomized acetabular fragment. To deal with this problem, we devised a computer program to support preoperative planning. Hip images obtained by computed tomography were loaded into our program, and a three-dimensional voxel model was created. Then, osteotomy was simulated and the pressure distribution was analyzed with a rigid-body spring analysis (computational nonlinear mechanical analysis). The three-dimensional pressure distributions in seven dysplastic hips were evaluated before and after virtual rotational acetabular osteotomy. A peak pressure was calculated for every 5 degrees of rotation of the acetabular fragment. The peak pressure decreased gradually and increased again afterward, indicating the optimal transposition of the acetabular fragment. The postoperative peak pressure decreased to about 40% in the most improved case. This program allows the hip joint mechanics to be evaluated easily so that the advantages and disadvantages of various surgical methods can be examined biomechanically prior to surgery.
Fibrous aerosols are of great importance to industrial hygienists because of the severe health risks that may be associated with inhaling such particles. Previous studies on measurement error due to overloading of fibers and nonfibrous particles on the collected sample indicate that a 100-1300 fiber/mm2 filter area is the best filter loading density to reduce bias in fiber counts. The present study investigated the upper fiber and particle concentration limits for reliable counting and identification and the possibility of a procedure for correcting observed fiber counts to account for fiber masking due to overlapping particles or fibers. A computer-generated grid was used to simulate the light microscope graticule field. The resolution of 2000 x 2000 was found to accurately represent the shape of the fibers and nonfibrous particles. Bivariate lognormal distributions were used to describe the length and width distributions of the fibers. The capability of distinguishing particle-overlapped fibers (defined as the resolution index), the coverage of the graticule field, the filter surface loading density, size distributions of fibers and particles, and the fiber-to-particle concentration ratio were the primary parameters in this study. The counting efficiency was found to consistently decrease with increasing filter surface loading density and decreasing resolution index. The recommended upper limit of filter surface fiber density depended not only on the number concentration ratio but also on the filter surface loading densities and size distributions of fibers and particles. The advantage of using a thoracic preseparator on counting efficiency was calculated and found to improve counting efficiency significantly when the count median diameter of nonfibrous particles was close to or larger than the thoracic 50% cutoff point of 10 microm.