Preprocessor Adapts Cardiovascular Signals to a Minicomputer

A laboratory-developed analog signal processor, driven by a conventional polygraph recorder and associated signal conditioning devices, provides automatic heart beat-by-heart beat preprocessing of various cardiovascular functions for input to a laboratory-type minicomputer. The technique of preprocessing individual functions, integrated with the minicomputer system which includes an A/D converter and teletype as input-output peripherals, provides a low-cost data acquisition and reduction system for the on-line computation and analysis of cardiovascular functions in experimental research applications. Such preprocessing more efficiently uses the minicomputer's memory to handle large amounts of information since the digitized data is in the form of one data sample, per function, per heart beat. Preprocessing analog data provides a low density data format and simplified software programs that are ideally suited for the utilization of a minicomputer in this on-line application.     

Radiology capital asset management

Radiology administrators are expected not only to take on the ultimate accountability for meeting the needs and challenges of present day-to-day operations, but also to plan for the future. Computer Aided Facility Management (CAFM), as a tool, enables radiology managers to obtain up-to-date data to manage their services. Using Autocad on a unix-based minicomputer as the graphical base generator and integrating information from a MUMPS-based minicomputer, the CAFM process can define areas to be studied for productivity and life cycle costs. From an analysis of radiology service, management was able to make solid judgement calls for equipment replacement and facility project renovation to effectively manage radiology resources.     

A clinically operational method for three-dimensional dose calculations

Three-dimensional dose calculations can now be performed for both photon and neutron beam therapy in reasonable times on a minicomputer. The method described is a scatter-air ratio-tissue-air ratio (SAR-TAR) model which, for any beam, finds the correct depth at each point in a patient even when the beam passes obliquely through more than one transverse section of the patient. Scatter dose is determined by performing a Clarkson integration over both angle and radial distance, with the correct depth of the beam calculated at both accumulation and scatter points. Doses are computed and displayed over a 0.33 cm sampling grid superimposed on each transverse CT slice used in treatment planning. Dose-volume histograms are made for the entire patient volume and for internal organs and target volumes outlined by the physician. The clinical efficacy of the method in therapy planning is demonstrated and a comparison is made between this method and single section two-dimensional methods.     

Maximizing the entropy of histogram bar heights to explore neural activity: a simulation study on auditory and tactile fibers

Neurophysiologists often use histograms to explore patterns of activity in neural spike trains. The bin size selected to construct a histogram is crucial: too large bin widths result in coarse histograms, too small bin widths expand unimportant detail. Peri-stimulus time (PST) histograms of simulated nerve fibers were studied in the current article. This class of histograms gives information about neural activity in the temporal domain and is a density estimate for the spike rate. Scott's rule based on modem statistical theory suggests that the optimal bin size is inversely proportional to the cube root of sample size. However, this estimate requires a priori knowledge about the density function. Moreover, there are no good algorithms for adaptive-mesh histograms, which have variable bin sizes to minimize estimation errors. Therefore, an unconventional technique is proposed here to help experimenters in practice. This novel method maximizes the entropy of histogram-bar heights to find the unique bin size, which generates the highest disorder in a histogram (i.e., the most complex histogram), and is useful as a starting point for neural data mining. Although the proposed method is ad hoc from a density-estimation point of view, it is simple, efficient and more helpful in the experimental setting where no prior statistical information on neural activity is available. The results of simulations based on the entropy method are also discussed in relation to Ellaway's cumulative-sum technique, which can detect subtle changes in neural activity in certain conditions.     

Autocorrelation techniques for measuring avian heart rates

Online computer methods have been developed to derive the heart rate of a bird from its telemetered electrocardiogram (e.c.g.). A PDP-8/L minicomputer, with real time clock and simple xy-display, is used for this purpose. Autocorrelation methods have been developed to deal with signals which are obscured by the electromyogram and electrical interference. These techniques produce reliable results in circumstances where more conventional methods are not dependable.     

Incidence of chromosomal imbalances in advanced colorectal carcinomas and their metastases

Comparative genomic hybridization (CGH) was used to screen 54 advanced colon carcinomas. i.e., 24 primary tumors and 30 metastases, for chromosomal alterations. Using a sensitive statistical method for the determination of DNA imbalances and histograms for analysis of the incidence of changes, we identified the DNA over-representation of chromosome 20q as the most common alteration being present in 100% of cases. High incidence deletions were observed on 18q21-18q23 (96%), 4q27-4q28 (96%), 4p14 (87%), 5q21 (81%), 1p21-1p22 (72%), 21q21 (74%), 6q16 (72%), 3p12 (66%), 8p24-8p21 (66%), 9p21 (64%), 11q22 (64%), and 14q13-14q21 (64%). Further frequent over-representation was found on 7q12-7q11.2 (75%), 16p11-16p12 (70%), 19p13 (70%), 9q34 (67%), 19q13 (67%), 13q34 (64%), 13q13 (64%), 17q21 (59%), 22q11 (61%), 8q24 (57%), and 1q21 (57%). Pronounced DNA gains and losses being defined as regions in which the ratio profiles exceeded the values of 1.5 and 0.5, respectively, frequently colocalized with peaks of incidence curve. The use of difference histograms for the comparison of tumor subgroups as well as case-by-case histogram for the analysis of 15 paired tumor samples identified several of the above alterations as relevant for tumor progression and metastasis formation. The study identified additional loci and delineates more precisely those that have been previously reported. For comparative purposes, we have made our primary data (ratio profiles, clinicopathological parameters, histograms) available at the interactive web site http://amba.charite.de/cgh, where the incidence of changes can be determined at individual loci and additional parameters can be applied for the analysis of our CGH results.     

Early and late components in cat renshaw cell responses to random stimulation of motor axons: Their differential sensitivity to preceding activation

Lumbosacral Renshaw cells were activated by random stimulation of motor axons in muscle nerves or ventral roots. The stimulus patterns had mean rates of 9.5–13 or 20–23 pulses per second. The Renshaw cell responses were evaluated by two kinds of peristimulus-time histograms. “Conventional” peristimulus-time histograms were calculated by averaging the cell discharge with respect to all the stimuli in a train. “Conditional” peristimulus-time histograms were determined by averaging the cell discharge with respect to the second (“test”) stimulus in pairs of stimuli which were separated by varied intervals. The effects of the conditioning stimuli were evaluated after correcting for the effect of linear superposition of the conditioning and test stimuli.

The conventional peristimulus-time histograms showed an excitatory response which often consisted of two distinct components: a narrow and high “early” peak and a broad and low “late” elevation of firing probability. The early and late excitatory components were conditioned in different ways. Whereas the late component was virtually always depressed, the early component showed three patterns: (1) uniform depression; (2) uniform facilitation; (3) a mixture of depression and facilitation. Frequency responses (coherence and gain estimates) were also calculated separately for the cell discharges underlying either the early or the late components. The estimates for the “late spikes” showed a stronger decline with increasing frequency than those for the “early spikes”.

The origin of the different conditioning effects probably lies in a combination of pre and postsynaptic factors. They may play a role in tremor mechanisms.     

A system for interactive film analysis.

An interactive, minicomputer system has been constructed for analyzing dynamic phenomena recorded on movie film in a developmental biology laboratory. The minicomputer interfaces a stop-motion, variable speed projector, a digitizing pen, and real-time graphics display equipment. An analyst uses the pen to digitize features in a film, e.g. by following a cell. A computer-generated animation portraying all data entered is superimposed on the film image and synchronized with it. Noteworthy system features include: image overlays on a large screen, data entry with the projector running, large data capacity, computer control of the projector, and convenient data entry tools.     

Microfiche as a medium for the long-term storage of laboratory computer records.

The chemical pathology requests on 180 000 patients a year are stored on microfiche, occupying 72 mm of shelf space. They are produced by a sequence of three computer programs which remove data from disc on to magnetic tape using the laboratory's Digital Equipment Corporation PDP 11/34 minicomputer. Processing on to microfiche is performed by a bureau. The magnetic tape is available for retrospective research and management studies in one-month periods.     

Mathematical model of renal regulation of urea excretion

A mathematical model of transport processes in the ascending limbs (a.l.), collecting ducts (c.d.), and surrounding interstitium-capillary plexus (i.c.p.) of the renal medulla has been developed and applied to an investigation of mechanisms which may be involved in renal tubular regulation of urea excretion. Solute and water balance equations for perfectly-mixed compartments in series describe the transport processes in the a.l., c.d., and i.c.p. Solute species considered are urea, salt (NaCl), and an idealised ‘nonreabsorbable solute’ which accounts for miscellaneous substances accumulated in the c.d. The membrane transport equations used in the model describe solute movement by passive diffusion, solvent drag, and active transport; and water movement by osmosis. Model parameters are evaluated from published experimental data. Digital computer solutions of the model equations indicate that virtually all experimental observations pertaining to the regulation of urea excretion can be explained by an increase in the solvent drag of urea from the cortical and medullary c.d. Therefore, the need to postulate an active transport of urea from the c.d. to explain the regulation of urea excretion is obviated.     

Heterogeneous computer network for real-time hemodynamic signal processing

A computer network is described that allows real-time processing, graphical monitoring and off-line analysis of blood pressure, nervous activity and Doppler signals recorded in conscious rats. Real-time processing is performed by an acquisition station using a powerful microprocessor, allowing extraction and storage of several characteristic parameters from each cardiac cycle and real-time graphical monitoring. The experimenter can thereby follow the time evolution of the hemodynamic parameters. Experimental data are sent through the local network to a workstation that ensures off-line processing such as chronograms, histograms and statistical analyses.     

Multichannel automatic foetal movement monitoring and classification system

The purpose of this work was to develop a compact, noninvasive and objective tool for foetal movement monitoring and classification. Four tocodynamometers were used as movement transducers and their output signals processed by a minicomputer on which a microprocessor real time compatible algorithm was developed. The algorithm was based on time domain analysis where the parameters, such as averaging intervals and threshold levels were optimised in a trial and error procedure to minimise undetected foetal movements and false detections on a set of nine pregnant women. The detection score was 92·2 per cent when short foetal movements were ignored.     

A video interface for behavioural recordings with applications

An interface which can transmit information from a TV camera to a minicomputer is described. The interface delivers addresses significant for the position of an animal in an observation arena. These addresses are then treated by a minicomputer assembler program. In our application, the length of visiting (duration), frequency of visits and latency of first visit to a specified field are recorded, together with an activity variable. The high IR sensitivity of the camera makes it possible to record the position of the animal relative to certain environmental objects under conditions of dimmed light.     

Characterisation of in vivo ovarian cancer models by quantitative 1H magnetic resonance spectroscopy and diffusion-weighted imaging

Magnetic resonance imaging (MRI) and spectroscopy (MRS) offer powerful approaches for detecting physiological and metabolic alterations in malignancies and help investigate underlying molecular mechanisms. Research on epithelial ovarian carcinoma (EOC), the gynaecological malignancy with the highest death rate characterised by frequent relapse and onset of drug resistance, could benefit from application of these molecular imaging approaches. In this study, MRI/MRS were used to characterise solid tumour models obtained by subcutaneous (s.c.) or intraperitoneal (i.p.) implantation of human SKOV3.ip cells in severe combined immunodeficiency (SCID) mice. In vivo MRI/MRS, ex vivo magic-angle-spinning (MAS), and in vitro (1)H-NMR measurements were carried out at 4.7 T, 9.4 T, and 9.4/16.5 T, respectively. MRI evaluation was performed by T1-, T2-, and diffusion-weighted (DW) multislice spin-echo imaging. The in vivo (1)H spectra of all tumour models showed a prominent resonance of total choline-containing metabolites (tCho). Quantitative in vivo MRS of both i.p. and s.c. SKOV3.ip xenografts showed that the mean tCho content was in the 2.9-4.5 mM range, with a mean PCho/tCho ratio of 0.99 ± 0.01 [23 examinations, 14-34 days post injection (dpi)], in good agreement with ex vivo and in vitro analyses. Myo-inositol ranged between 11.7 and 17.0 mM, with a trend towards higher values in i.p. xenografts at 14-16 dpi. The average apparent diffusion coefficient (ADC) values of SKOV3.ip xenografts [1.64 ± 0.11 (n = 9, i.p.) and 1.58 ± 0.03 x10(-3) mm(2)/s (n = 7, s.c.)] were in agreement with values reported for tumours from patients with EOC, while the mean vascular signal fraction (VSF) was lower (≤ 4%), probably due to the more rapid growth of preclinical models. Both s.c. and i.p. xenografts are valuable preclinical models for monitoring biochemical and physiopathological changes associated with in vivo EOC tumour growth and response to therapy, which may serve as the basis for further clinical development of noninvasive MR approaches.     

Mini-micro-mainframe computer marriage: Combining technologies in a radiology results reporting system

The minicomputer-based information system in the Department of Radiology at the Medical College of Georgia Hospital and Clinics was placed in service in February, 1982. This system represents a sizable investment in minicomputer hardware in addition to more than 6 years of software customization. One serious deficiency in the original system was the lack of a radiology results reporting facility. Several options were considered to provide the department with this capability. The most obvious option was retiring the existing system and replacing it with one of a number of commercial products already offering results reporting. In-house development of a reporting facility lent itself more readily to microcomputers than to the existing minicomputer system. Due to system customization, economic and time constraints, it was decided to merge an in-house developed microcomputer-based report module into our existing minicomputer system. The minicomputer was able to communicate with and transfer files to and from both micro and mainframe systems. Combining technologies allowed us to continue taking advantage of our sizable investment in money, time, and customization while providing a microcomputer-based report module. Radiology reports are now typed on microcomputer word processors and bulk transferred to the minicomputer. The minicomputer provides access to both unapproved and approved reports on system terminals throughout the department. It also enhances reports by merging patient demographics and registration information. Using existing communications facilities to the hospital mainframe system, reports are provided throughout the institution.     

Trigeminovascular nociceptive transmission involves N-methyl-d-aspartate and non-N-methyl-d-aspartate glutamate receptors

Interest in the fundamental mechanisms underlying headache, particularly the pathophysiology of migraine and cluster headache, has lead to the study of the physiology and pharmacology of the trigeminovascular system and its central ramifications. Cats were anaesthetized (60 mg/kg alpha-chloralose, i.p., along with halothane for all surgical procedures) and prepared for physiological monitoring. The animals were placed in a stereotaxic frame and ventilated. A midline craniotomy and C2 laminectomy were performed for access to the superior sagittal sinus and C2 dorsal horn, respectively. The sinus was isolated from the underlying cortex and stimulated electrically after the animals had been paralysed with gallamine (6 mg/kg, i.v.). Units linked to stimulation were recorded with a tungsten-in-glass microelectrode placed in the most caudal part of the trigeminal nucleus, the trigeminocervical complex. Signals from the neurons were amplified, filtered and passed to a microcomputer, where post-stimulus histograms were constructed on-line to analyse the responses to stimulation. Units responded to sagittal sinus stimulation with a typical latency of 8-10 ms. All units studied had a probability of firing of 0.6 or greater. Intravenous injection of the non-competitive N-methyl-D-aspartate receptor antagonist, dizocilpine maleate (4 mg/kg, i.v.), resulted in a substantial and prolonged blockade of firing of units in the trigeminocervical complex. Similarly, administration of the non-N-methyl-D-aspartate excitatory amino acid receptor blocker, GYKI 52466, lead to a dose-dependent inhibition of trigeminovascular-evoked responses in the trigeminocervical complex. These data demonstrate the participation of both N-methyl-D-aspartate- and non-N-methyl-D-aspartate-mediated mechanisms in transmission within the trigeminocervical complex, and suggest a clear preclinical role of glutamatergic mechanisms in primary headache syndromes, such as migraine and cluster headache.     

Relationship of metabolism and immunostimulating activity of peptidoglycan monomer in mice after three different routes of administration

[14C] Peptidoglycan monomer, GlcNAc-MurNAc-L-Ala-D-isoglutamine-meso-diaminopimelic acid (omega NH2)-D-Ala-D-Ala (PGM) was administered to mice by the intravenous (i.v.), subcutaneous (s.c.) or peroral (p.o.) routes. The data on distribution of radioactivity and excretion of radioactive products, as well as the data on immunostimulating effects are presented on the comparative basis for PGM administered by three different routes. When injected i.v. or s.c., the major part of applied radioactivity was found excreted in urine, partly as unchanged original compound and partly as the corresponding pentapeptide, L-Ala-D-isoglutamine-meso-diaminopimelic acid (omega NH2)-D-Ala-D-Ala. If administered p.o., the major part of the radioactivity was retained in the stomach and intestinal tract for several hours. The drop in radioactivity in these organs was followed by exhalation of 14CO2 thus indicating extensive degradation of the original molecule. PGM stimulates the humoral immune response to sheep red blood cells in mice if administered i.v. or s.c., but is completely inactive if administered p.o.. Thus, absence of immunostimulating activity following p.o. administration might be explained by extensive metabolic degradation of peptidoglycan monomer.     

A computer method for cardiac radionuclide kymography

A technique is presented for the generation of cardiac kymograms by a minicomputer from the data collected during routine multi-image gated cardiac blood pool imaging. A radionuclide kymogram is a data processing and display technique which permits quantitative assessment of boundary motion for cyclic functions such as ventricular contraction. Multiple kymograms can be obtained without any modification of the routine patient data collection protocol. The kymograms focus the observer's attention on specific segments of the cardiac chambers permitting easier extraction of quantitative information to add to these standard wall motion studies.     

The effect of calcium ions and temperature on the binomial parameters that control acetylcholine release by a nerve impulse at amphibian neuromuscular synapses.

1. A study has been made of the effects of changing the external calcium concentration, [Ca](o), and the temperature on both the number of quanta available for release by the nerve impulse (n) as well as the increase in release probability of a quantum p(t) during the release period (from 0 to T) following a nerve impulse at synapses in amphibian striated muscle.2. When [Ca](o) was increased in the low range from 0.25 to 0.4 mM at 18 degrees C, the average quantal content of the e.p.p. (m) increased as the fourth power of [Ca](o) and this was primarily due to a third power dependence of n on [Ca](o); the dissociation constants and power dependence of n on calcium determined in the [Ca](o) range from 0.25 to 1.0 mM were successfully used to predict the changes in size of the e.p.p. in the very high [Ca](o) range from 1 to 10 mM. When the temperature was increased from 7 to 18 degrees C in a [Ca](o) of 0.6 mM or 0.35 mM, n increased with a Q(10) of 2.5.3. When [Ca](o) was increased in the range from 0.25 to 1.0 mM at 18 degrees C, the probability that a quantum initially available for release is released during the release period (p(T)) was very sensitive to [Ca](o), increasing as the third power of [Ca](o) and with a dissociation constant of 0.13 mM. When the temperature was increased from 7 to 18 degrees C in a [Ca](o) of 0.6 mM or 0.35 mM, p(T) decreased.4. The histograms of latencies of individual quanta following a nerve impulse was very temperature dependent: the time to peak of the histograms (i.e. the interval in which most quanta fell) had a Q(10) of over 4 as did the time constant of decline of the histograms in the temperature range from 7 to 18 degrees C.5. The average number of quanta released up to time t during the release period following a nerve impulse, namely np(t), was well described by a stochastic process in which p(t) was determined by two reactions; one of these reactions released available quanta from the nerve terminal whilst the other made some of the available quanta unavailable for release by the nerve impulse.     

Scoliosis evaluation utilising truncal cross-sections

In scoliosis, two basic structural changes, i.e. lateral flexion and axial rotation, result in the characteristic spinal deformity. Radiography has proved satisfactory in measuring the lateral flexion deformity. However, at present there is no satisfactory method to measure the rotational deformity. A method to measure the latter deformity by drawing out cross-sections of the trunk has been developed: the projection of a horizontal laser beam on the body surface is detected by an inclined line sensor camera. The laser and line sensor camera are simultanelously moved around the patient and the camera output data are converted, by a minicomputer, into the cross-section on a graphic display or an x-y plotter. To evaluate the deformity of the cross-sections quantitatively, we introduced deformity indices and proposed algorithms for their calculation. Measuring crosssections of 59 scoliosis patients, we analysed the relationship between the deformity indices and the Cobb angle.