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Biomedical subjects

S A Reid

Publications and source records attributed to S A Reid.

At least 19 recordsLinked to original sources

3-D computer animation of electrophysiological responses.

Traditional methods for displaying electrophysiological data, that use time as the axis on a plot, are inadequate for displaying data from simultaneous multi-channel recordings. New methods proposed here plot the instantaneous value of the data on a third axis over a 2-dimensional spatial map of the tissue. The resulting 3-D computer-generated surfaces are animated over time to reveal simultaneous coherent waves of activity over the entire slice. This method was implemented for displaying multi-channel evoked potential data from rat hippocampal and human cortical slices. In rat hippocampal slice, stimulation of the Schaffer collateral-commissural pathway in stratum radiatum (SR) near CA2 elicited evoked extracellular responses along the length of CA1 from the alveus to stratum lacunosum moleculare (SLM). 3-D plotting and subsequent animation of these responses translated differential latencies of activation elicited across the slice into coherent moving patterns. These evoked waves of extracellular activity appeared to propagate along hippocampal laminae and were not readily visible in the individual plots. Human temporal cortical slices were stimulated in the white matter and evoked responses recorded in an array format. Upon plotting and animation, activity was seen to propagate vertically to the pial surface and thereafter move radially away from the stimulation site. Animation of 3-D plots of electrophysiological activity can provide instantaneous visual information on correlated changes in amplitude and latency over an entire brain slice. This means of displaying data can reduce a large number of complex wave forms to simple events and allow the simultaneous visualization of general patterns of activity in a large group of neurons.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Absence of cortical white matter changes in three patients undergoing long-term vigabatrin therapy.

Chronic administration of the experimental antiepileptic drug vigabatrin (gamma-vinyl GABA) to animals has been shown to cause dose-dependent neuropathological changes characterized by a microvacuolation in specific white matter tracts. This finding has led to some concern as to whether similar pathologic changes might occur in patients taking this medication. Here we report on analysis of tissue specimens taken during neurosurgery from three patients undergoing chronic vigabatrin therapy (4 g/day). The first patient, a 34-year-old woman, had taken vigabatrin for 2 years prior to surgery, the second, a 50-year-old man, had taken the drug for 1 year, and a 34-year-old man had taken the drug for 5.3 years. For comparison, similar specimens were taken from three other patients not taking vigabatrin who were undergoing surgery for intractable epilepsy. Specimens from each subject were prepared in an identical manner and examined with light and electron microscopy. All specimens were examined in a blinded fashion. There was some minor nonspecific myelinic splitting seen in both controls and vigabatrin-treated patients but there was no evidence for any drug-induced lesions similar to that seen in experimental animals.

Adult

Epidural lipomatosis in steroid-treated patients.

Epidural lipomatosis is a condition in which excess adipose tissue is deposited circumferentially about the spinal cord in the epidural space. It is most frequently seen in patients on chronic steroid treatment for a variety of medical problems and can present as nonspecific back pain, radiculopathy, or frank spinal cord compression. Diagnosis and treatment have generally relied on multi-level decompressive laminectomy after myelography and computed tomography. The immunocompromised state and the reported postoperative mortality (22%) of these patients, however, suggests that nonoperative therapy may be preferable whenever possible. Five cases of epidural lipomatosis are reported, and previous literature is reviewed for presentation, evaluation, and treatment of this condition.

Adult

Inhibition of hematopoietic progenitor colony growth by a monoclonal antibody against the transferrin receptor: comparison of unconjugated antibody with an immunotoxin containing recombinant ricin A chain.

We studied an immunotoxin consisting of recombinant ricin A chain (rRA) conjugated to 454A12 MoAb, a monoclonal antibody which recognizes an epitope on the human transferrin receptor, and compared the ability of 454A12 MoAb-rRA immunotoxin to inhibit the growth of erythroid burst-forming units (BFU-e) and myeloid colony-forming units (CFU-c) with unconjugated 454A12 MoAb. A significant reduction in BFU-e colony growth was observed at 0.001 microgram/ml of 454A12 MoAb-rRA versus 0.1 microgram/ml of unconjugated 454A12 MoAb (p = 0.005). Comparison of the effects of 454A12 MoAb-rRA and 454A12 MoAb on myeloid colony development gave markedly different results. Unconjugated antibody had no effect on CFU-c colony growth; in contrast, 0.01 microgram/ml of 454A12 MoAb-rRA reduced the number of colonies from 139 per 1 X 10(5) to 75 per 1 X 10(5) cells plated (p = 0.0005). No myeloid progenitor colonies developed at 0.1 microgram/ml of immunotoxin. These observations suggest that 454A12 MoAb-rRA inhibits growth by a potent, ricin A chain-mediated toxic effect on any proliferating cells expressing transferrin receptors, whereas the 454A12 MoAb exerts a selective inhibitory effect primarily on erythroid progenitors by perturbing the transferrin cycle. While growth factor receptors expressed on hematopoietic cells represent promising targets for immunotoxin therapy, our data indicate that an immunotoxin could inhibit cellular proliferation by a different mechanism than the corresponding unconjugated MoAb. Depending on the antibody used, these differences may be important in trials using immunotoxins for in vivo treatment or in vitro purging of malignant hematopoietic cells.

Antibodies, Monoclonal

TDAT--time domain analysis tool for EEG analysis.

An interactive design and analysis tool for displaying and quantifying multiple channels of data is presented. The system allows one to easily visualize multiple data channels and simultaneously observe the effects of filters on the data and to evaluate signal detection algorithms. The software is designed for a workstation environment; it will find application in a variety of applications where one needs to simultaneously visualize multiple data channels. TDAT is being used for the design and evaluation of filters and detection algorithms for electroencephalogram (EEG) waveforms, and it is serving as a prototype of a paperless system to be used by electroencephalographers. This paper describes the general software structure of the system and illustrates many of the system features with examples.

Algorithms

Efficacy and safety of vagus nerve stimulation in patients with complex partial seizures.

A clinical trial of chronic intermittent vagal stimulation in five patients suggests that the procedure may be safe and effective as adjunctive treatment of medically intractable seizures of partial onset. Patients tolerated well the implantation of the neurocybernetic prosthesis and the vagal stimulation without serious physiological or lifestyle changes. Stimulation of the vagus nerve either reduced the seizure frequency or decreased the duration or intensity of seizures. Adverse side effects were limited to a tingling sensation in the throat and hoarseness during stimulation. A major complication was mechanical interruption of the wire-electrode circuitry, with consequent cessation of stimulation. The small number of patients and the relatively short follow-up period make this a pilot study, but the results are promising.

Adult

Vagus nerve stimulation in humans: neurophysiological studies and electrophysiological monitoring.

Evidence from studies of experimental animals indicates that electrical stimulation of the vagus nerve alters behavioral and electrographic seizure activity. We report on effects of electrical stimulation of the vagus nerve in five patients with medically intractable seizures as part of a clinical trial of chronic vagal stimulation for control of epilepsy. The mechanism of action of the vagal antiepileptic effect is unknown, and it is hoped that analysis of electrophysiological effects of vagal nerve stimulation will help elucidate which brain areas are affected. Stimulation of the left vagus nerve in the neck was accomplished with a programmable implanted stimulator. Effects of stimulus amplitude, duration, and rate were studied. Noncephalic reference recording of the vagus-nerve-evoked potential showed some unusual properties: a scalp negative component occurred with latency of 12 ms, very high amplitude (up to 60 microV), and widespread scalp distribution. Field distribution studies indicate that this potential is generated in the neck, in the region of the stimulating electrodes. Muscle paralysis confirms this observation. Stimulation at various frequencies had no noticeable effect on electroencephalographic (EEG) activity regardless of whether the patient was under general anesthesia, awake, or asleep.

Adult

Distribution and physical properties of BCA200, a Mr 200,000 glycoprotein selectively associated with human breast cancer.

Of 122 mouse monoclonal antibodies selective for human breast cancer, 13 immunoprecipitated an acidic glycoprotein from SK-Br-3 and ZR-75-30 human breast cancer cells. The antigen (BCA200) migrates with an apparent molecular weight of 200,000 on reducing and 180,000 on nonreducing sodium dodecyl sulfate-polyacrylamide gel electrophoresis, suggesting a single polypeptide chain with a folded domain stabilized by a disulfide bond. Cross-blocking and sandwich immunoassays detected at least three distinct antigenic determinants on BCA200. Scatchard experiments measured 1,000,000 to 5,000,000 antigen copies per SK-Br-3 cell. The tissue distribution of BCA200 was studied using two monoclonals to different epitopes. Neither antibody stained any cells in human blood. When frozen sections of 20 normal human tissues were immunoperoxidase stained, the only positive structures were mucinous glands of colon, transitional epithelium of bladder, sweat glands of skin, and acinar epithelium of breast. Antibody 454C11 stained 16 of 21 breast tumor frozen sections and 9 of 12 breast cancer cell lines, while antibody 520C9 stained 5 of 20 breast tumors and 4 of 10 breast cancer lines. Cross-reaction was observed with lung, prostatic, pancreatic, endometrial, and ovarian cancer, but not with lymphoma, melanoma, colon, stomach, bladder, or esophageal cancer. When conjugated to ricin A chain, 10 of 13 antibodies produced immunotoxins selectively cytotoxic to SK-Br-3 breast cancer cells.

Antibodies, Monoclonal

Spontaneous epileptiform discharges in isolated human cortical slices from epileptic patients.

Human epileptic in vitro brain slices were obtained at ablative neurosurgical procedures and examined for spontaneous extracellular field potentials. Electrical events resembling interictal spikes and seizure discharges were observed in tissue from the electrocorticographic epileptic foci, but not in control tissue. It appears that important differences between the epileptic focus and normal tissue are maintained in vitro.

Cerebral Cortex

Toward the ideal electrocorticography array.

Several features desirable in the design of electrocorticography arrays are listed. A new electrocorticography system is described and compared with types that are commercially available. This system offers several advantages over older systems and results in significant saving of time in the operating room.

Cerebral Cortex

NeuroSIG: the computer network of the Congress of Neurological Surgeons.

A sophisticated computer network has been developed specifically for use by the Congress of Neurological Surgeons. This network provides a variety of communication and information features. These include public and private message transmission, teleconferencing, numerous data libraries, programs that may be downloaded and executed on the user's own computer, high resolution color graphics image transmission, an extensive neurosurgical database, and extensive on-line "help" features. The system can be accessed using almost any personal computer and a telephone modem.

Computer Communication Networks

Changes in the mineral density distribution in human bone with age: image analysis using backscattered electrons in the SEM.

We report a study to test the feasibility of studying mineral density distributions in bone using the backscattered electron signal in scanning electron microscopy. Samples were human sixth ribs ranging in age from 8 weeks to 59 years, embedded in polymethylmethacrylate (PMMA), cut, polished, and carbon coated. The proportions of pixels falling in a uniform set of gray level slices of the BSE signal were determined using a microcomputer-based image analysis system interfaced directly to the SEM. The amount of high-density bone gradually increased with age at the expense of low-density bone, and there was an associated compression of the range of the mineral density distribution. Age-related differences were noted between the density distributions in the outer and inner rib cortices. The distribution in the inner cortex in neonates was influenced by the inclusion of densely mineralized endochondral bone and cartilage trabeculae formed at the growth cartilage zone. In adults it appeared that greater bone turnover occurred in the outer cortex, perhaps reflecting a differential mechanical loading across the rib. The technique enabled rapid, unbiased discrimination between the bone of neonates, children, and adults.

Adolescent

Micromorphological characterisation of normal human bone surfaces as a function of age.

Endosteal surfaces of human bone specimens, principally from the sixth rib, from subjects ranging in age from seven weeks to 87 years were studied using the secondary electron imaging mode in the scanning electron microscope. Specimens were examined after the removal of cells only, or after the removal of cells and organic matrix. Morphological differences made it possible to identify the age group to which a specimen belonged. The most obvious of these was the ratio of active to resting bone surfaces, which collagen matrix which was deposited at endosteal surfaces was different in the different age groups. In neonates, collagen was organised as a parallel fibred continuum. It was present in more discrete bundles in adults, although these still branched and anastomosed with one another. The bundles were parallel over limited domains which described large angles with respect to one another. The conformation of resorbed surfaces indicated that the behaviour pattern of osteoclasts changes with age. Shallow gutters, or annular zones around resorption bays were most common in neonates. The elongation ratio of resorption tracks was greatest in infants and juveniles, indicating that osteoclast translocation was greatest during resorption at these ages. The texture of the floors of resorption bays was smooth in specimens from subjects up to 13 years, while in adults the collagen fibre bundle organisation in the resorbed tissue was often visible. This difference may reflect a more equal mineralization in the ground substance and collagen compartments of the bone matrix in children than in adults.

Adolescent

A study of lamellar organisation in juvenile and adult human bone.

The scanning electron microscope (SEM) has been used to study the three-dimensional organisation of collagen in slices of human rib and femur which were "etched" by chick osteoclasts, mechanically isolated and grown on their surfaces in vitro. Collagen organisation in the two bones showed a spectrum of appearances, ranging from lamellae of approximately equal thickness, but alternating fibre orientations, to an almost exclusive orientation of collagen apparently in a longitudinal direction. The rib contained a smaller component of transversely oriented collagen which may be related to a different functional loading. The thickness of circumferential lamellae was less than that of osteonal lamellae in the two adult ribs examined. Also, in the rib there was a trend towards increased average lamellar thickness with age in the range studied. This may be related to the fact that more of the lamellae in the rib cortex in children have been formed circumferentially. Correlation of results obtained with the SEM and the polarised light microscope (PLM) from the same substratum demonstrated that the latter grossly exaggerated the apparent component of collagen with a transverse orientation. This will always be true unless sections comparable with the lamellar thickness are used with the PLM.

Adult

Effect of mineral content of human bone on in vitro resorption.

Osteoclasts, mechanically isolated from chick long bones, were grown in vitro on slices of human rib and femur. Evidence of their activity was assessed by secondary electron and backscattered electron (BSE) imaging in the SEM. BSE imaging was also used to study the relative degree of mineralisation of the bone matrix in which resorption had taken place. All bone phases were resorbed, from osteoid through to densely mineralised interstitial bone and reversal (cement) lines. Resorbing osteoclasts crossed reversal lines between osteons of different mineral density and moved both from higher to lower and lower to higher density phases. Where single loci spanned reversal lines, and thus breached bone of two different mineral densities, depth of demineralisation was inversely related to mineral density. The presence of an annular zone around some resorption loci, which may be caused by demineralisation beneath the osteoclast clear zone, was confirmed. Also, BSE imaging of polished substrata showed that significantly more osteoclastic activity had occurred at their surfaces than was apparent from the amount of cavitation present.

Adult

Scanning electron microscopy in bone pathology: review of methods, potential and applications.

This article reviews the applications of SEM methods to human bone pathologies referring to studies made at UCL. We consider the methods which may be most suitable; these prove to be not "routine" in the context of most bio-medical applications of SEM. Valuable information can be obtained from a bone sample if its edges are ground flat, before making either a matrix surface preparation by washing away all the cells or a mineralizing front preparation, by also dissolving the osteoid-for which hydrogen peroxide is recommended to produce a robust specimen. BSE contrast from a cut block surface can be used to measure bone phase volume. SE contrasts from natural surfaces (trabeculae, canals and lacunae) can be used to study forming, resting and resorbing surfaces both qualitatively and quantitatively (except in the case of histological osteomalacia, where the existence of osteoid will go undetected and reversal lines will be difficult to distinguish from recently resorbed surfaces). We also recommend the use of PMMA embedded bone blocks, which can be used as obtained from the pathologist, but are better embedded by a more rigorous procedure. BSE image analysis can be used to quantitate bone density fractions opening up a completely new investigative method for the future. Osteoid can be measured automatically using CL if the bone sample is block stained with brilliant sulphaflavine before embedding or if a scintillant is added to the embeddant. We give examples of observations made from a number of bone diseases: vitamin D resistant rickets, osteogenesis imperfecta; osteomalacia; osteoporosis; hyperparathyroidism; fluorosis; Paget's disease; tumour metastasis to bone.

Adolescent

Membrane electrical properties and prediction of motor-unit type of medial gastrocnemius motoneurons in the cat.

Membrane electrical properties [time constant, action potential afterhyperpolarization (AHP), rheobase, input resistance, and axonal conduction velocity] were measured in motoneurons of cat medial gastrocnemius (MG) motor units. Motor units were classified on the basis of their mechanical responses as fast twitch, fast fatiguing (FF); fast twitch with intermediate fatigue resistance (FI); fast twitch, fatigue resistant (FR); or slow twitch, fatigue resistant (S; 11, 22). Motoneuron membrane time constant, estimated from the voltage response at the onset or termination of long (50-100 ms) current pulses and corrected for voltage-response nonlinearities (32), was found to differ significantly among the major motor-unit types, increasing in the order FF less than FR less than S. Afterhyperpolarization magnitude, half-decay time, and duration were all significantly greater for the fast (FF + FI + FR) versus the slow (S) motor units. The AHP half-decay time was correlated with muscle unit twitch time over the entire motoneuron population and within the type S motor-unit population. There was no significant correlation between twitch time and AHP half-decay time among the types FF and FR motor-unit populations. In agreement with previous studies, we found a significant difference in both rheobase and input resistance among the major motor-unit types, with rheobase increasing in the order S less than FR less than FF and input resistance decreasing in that order (S greater than FR greater than FF). The differences in input resistance were present both before and after correcting for voltage-response nonlinearities (32). Also in agreement with previous studies, the mean axonal conduction velocity was significantly faster among the fast (FF + FI + and FR) compared with the slow (S) motor units. These data were used to examine the properties alone to determine motor-unit type, which has traditionally been defined on the basis of the muscle unit's mechanical properties (11, 22). We used a discriminant analysis program to classify 73 mechanically typed motor units for which we had measures of rheobase, input resistance, membrane time constant, and AHP half-decay time. This model was able to properly classify 71 of the 73 motor units of this data set, indicating that the motor units of this data set could be grouped into three categories representing the three major motor-unit types (FF, FR, and S) on the basis of their rheobase, input resistance, membrane time constant, and AHP half-decay time.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials