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Biomedical subjects

A B Schwartz

Publications and source records attributed to A B Schwartz.

At least 19 recordsLinked to original sources

Neural signals for command control and feedback in functional neuromuscular stimulation: a review.

In current functional neuromuscular stimulation systems (FNS), control and feedback signals are usually provided by external sensors and switches, which pose problems such as donning and calibration time, cosmesis, and mechanical vulnerability. Artificial sensors are difficult to build and are insufficiently biocompatible and reliable for implantation. With the advent of methods for electrical interfacing with nerves and muscles, natural sensors are being considered as an alternative source of feedback and command signals for FNS. Decision making methods for higher level control can perform equally well with natural or artificial sensors. Recording nerve cuff electrodes have been developed and tested in animals and demonstrated to be feasible in humans for control of dorsiflexion in foot-drop and grasp in quadriplegia. Electromyographic signals, being one thousand times larger than electroneurograms, are easier to measure but have not been able to provide reliable indicators (e.g., of muscle fatigue) that would be useful in FNS systems. Animal studies have shown that information about the shape and movement of arm trajectories can be extracted from brain cortical activity, suggesting that FNS may ultimately be directly controllable from the central nervous system.

Electric Stimulation Therapy

A method for detecting the time course of correlation between single-unit activity and EMG during a behavioral task.

The chance that a change in excitability of one neuron leads to a change in excitability of another is likely to vary within a single volitional act. This temporal variability in functional connectivity is impossible to assess with standard analytical procedures to accurately that measure the correlation between such elements. This reports describes a technique designed to overcome this limitation by expressing a correlation measure calculated repeatedly in short epochs throughout a behavioral trial. The activity of two elements, a motor cortical neuron and a shoulder muscle, that might take place during a drawing task was first simulated so that the correlation could be manipulated. Various correlation algorithms (standard cross-correlation, spike-triggered average, impulse-response function, impulse-response surface) were tested with these data. Spike trains from a monkey's motor cortex and rectified EMG from its posterior deltoid muscle were compared using the same techniques and shown to have a correlation that changed in a characteristic manner throughout a task that required the monkey to draw a sinusoid.

Algorithms

The effects of recombinant human erythropoietin on mean corpuscular volume in patients with the anemia of chronic renal failure.

In historical studies erythropoietin stimulated bone marrow was shown to produce less stable, macrocytic, "stress erythrocytes". Recent work from our lab suggests that erythropoietin serves as both a growth factor and as a survival factor. To investigate the effects of recombinant human erythropoietin (rHuEPO) on development of red blood cell size of these longer lived erythrocytes, rHuEPO in 50-150 U/kg/dose was administered to patients with the anemia of chronic renal failure (CRF). Mean corpuscular volume (MCV) was determined at control, short term (n = 117, avg. 53 d), intermediate term (n = 73, avg. 136 d) and at long term (n = 66, avg. 221d) for effects of rHuEPO. Statistical evaluation at these time points was made comparing all patients to themselves as their own controls and using contingency tables for distribution of RBC size change. MCV at both short term (p = .02) and intermediate-term (p < .01) was decreased; there was no change (p = .71) at the long term. Analysis of distribution showed a significant (p < .01) trend toward microcytosis at short- and intermediate terms. This decrease of MCV and trend toward microcytosis is consistent with iron deficiency secondary to the early, rapid increase in bone marrow iron utilization and early increased reticulocytosis. Previous reports from our laboratory coupled with data presented in this report refute earlier findings that rHuEPO creates a "stress" mechanism producing less stable macrocytes.

Anemia, Hypochromic

Direct cortical representation of drawing.

How the intention to act results in movement is a fundamental question of brain organization. Recent work has shown that this operation involves the cooperative interaction of large neuronal populations. A population vector method, by transforming neuronal activity to the spatial domain, was used to visualize the motor cortical representation of the hand's trajectory made by rhesus monkeys as they drew spirals. Hand path was accurately reflected by a series of population vectors calculated throughout the task. A psychophysical rule relating speed to curvature, the "power law," was found in this cortical representation. The relative timing between each population vector and the corresponding portion of the movement was variable. The population vectors only preceded the movement in a predictive manner in portions of the spiral where the radius of curvature was greater than 6 centimeters. These results show that the movement trajectory is an important determinant of motor cortical activity and that this aspect of motor cortical activity may contribute only to discrete portions of the drawing movement.

Algorithms

Distributed motor processing in cerebral cortex.

Responding to a visual cue requires processing throughout many areas in the brain. The anatomical pathways connecting these diffuse areas are numerous. One way to study the cognitive processing associated with volitional movement is to identify common physiological properties in each area. Recently, the discovery that neuronal activity is broadly tuned in many of these cortical areas has led to new insights into the physiological structure of the process underlying cognition in this distributed system.

Animals

Motor cortical activity during drawing movements: population representation during sinusoid tracing.

1. Monkeys were trained to trace sinusoids with their index fingers on a planar surface. During this task, both the direction and speed of movement varied continuously. Activity of individual units in the precentral gyrus contralateral to the moving arm was recorded as the task was performed. These cells responded to passive movement of the shoulder and/or elbow. The relation between discharge rate and movement direction for these individual cells could be described with a cosine tuning function. 2. Data recorded as the sinusoid was traced were divided into 100 bins as each cell was studied during the experiment. In each bin, the activity of a particular cell was represented by a vector. The vector ("cell vector") pointed in the direction of finger movement that corresponded to the highest rate of neuronal discharge. This direction, referred to as the preferred direction, corresponded to the peak of the cosine tuning function. The direction of the vector was constant between bins, but the magnitude of this cell's vector was a function of the instantaneous discharge rate. 3. This cell vector is a hypothetical contribution of a single cell to the population response comprised of 554 similarly derived vectors from different cells. The population response was represented as the vector that resulted from forming the sum of the vector contributions from the individual cells. A separate calculation was made for each bin, resulting in 100 population vectors for each sinusoid. 4. Within a given time series of population vectors, their lengths and directions varied in a consistent relation to the tangential velocity of the drawing movement.(ABSTRACT TRUNCATED AT 250 WORDS)

Algorithms

Motor cortical activity during drawing movements: single-unit activity during sinusoid tracing.

1. This study examines the neuronal activity of motor cortical cells associated with the production of arm trajectories during drawing movements. Three monkeys were trained to perform two tasks. The first task ("center----out" task) required the animal to move its arm in different directions from a center start position to one of eight targets spaced at equal angular intervals and equal distances from the origin. Movements to each target were in a constant direction, and the average rate of neuronal discharge with movements to different targets varied in a characteristic pattern. A cosine tuning function was used to map each cell's discharge rate to the direction of arm movement. This function spanned all movement directions, with a peak firing rate in the cell's preferred direction. 2. The second task ("tracing" task) required the animal to trace curved figures consisting of sine waves of different spatial frequencies and amplitudes. Both the speed and direction changed continuously throughout these movements. The cosine tuning function derived from the center----out task was used to model the activity of the cell during the tracing of sinusoids in the second task. Sinusoidal data were divided into 20-ms bins; instantaneous direction, speed, and discharge rate were analyzed bin by bin. This provided a way to compare directly the tuning parameters during a task with constant direction to a task where the direction varied continuously. 3. Movement direction as it changed during the tracing task was an important factor in the discharge pattern of cells that had discharge patterns that could be represented by the cosine tuning function. 4. The modulation of discharge rate during figure tracing depended on both the cell's preferred direction and the orientation of the figure. The activity of cells with preferred directions perpendicular to the axis of the sinusoidal figure was most modulated, whereas the activity of those cells with preferred directions aligned to the figure's axis was least modulated. 5. The cells with modulated activity tended to have firing rates that differed from the predicted cosine tuning function during the sinusoidal movements for those portions of the trajectory where the movement direction was in the cell's preferred direction. 6. Finger speed during figure tracing varied inversely with path curvature with the same relation that has been found during human drawing. To assess the relation of instantaneous speed to discharge rate, the component of the discharge pattern related to direction was subtracted from the total discharge.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals

RBC improved survival due to recombinant human erythropoietin explains effectiveness of less frequent, low dose subcutaneous therapy.

Effectiveness of less frequent, once weekly, low dose subcutaneous recombinant human erythropoietin (rHuEPO) in maintaining 35% hematocrit in patients with chronic renal failure, predialysis and ESRD receiving dialysis, is dependent on rHuEPO induced prolonged RBC survival. One year of weekly rHuEPO doses to 7 patients originally part of the National Cooperative Protocol were evaluated for a total of 372 weeks for an average of 53 weeks per patient. The original 8 to 12 week dosage was directed by protocol for units per dose at 3 doses per week (4 IV, 3 subcutaneous). Thereafter, all doses were subcutaneous. Units/dose and doses/week were titrated to keep hematocrit at 35-38%. Dosage reduction of rHuEPO was determined by two investigators at the time of each examination. Statistical correlation was performed on effect of rHuEPO on 51Cr T1/2 RBC survival changes and changes of rHuEPO weekly doses. Patients evaluated at specific time points in the study were compared to themselves as their own controls by paired t-test analysis. The long-term increased RBC count correlated with prolonged RBC survival by 51Cr T1/2 rather than reticulocytosis. A relatively increased ease of sustaining the target hematocrit of 35% was demonstrated from the 8th week to 1 year. Thirty-two percent of the expanded RBC mass was older at 12 weeks and 22% was older at 1 year. rHuEPO dosage was reduced to 27% at weeks 8-12, to 21% at weeks 20-24, and to 38% at 1 year corresponding to prolonged RBC survival. 51Cr T1/2 increased from 21.6 days control to 28.6 days at 12 weeks and 26.3 days at 1 year.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Cardiovascular hemodynamic effects of correction of anemia of chronic renal failure with recombinant-human erythropoietin.

The results of 8 to 12 weeks of treatment of the anemia of uremia with rHuEPO in patients with chronic renal failure and uremia are: a sustained increased hematocrit; increased RBC mass, and subsequent increased MAP; and increased TPRI. The observed trends of decreased LVEF, and echo Doppler evidence of a trend toward LV systolic and diastolic dysfunction, although not individually statistically significant, represent 3 separate evaluation techniques coupled with hypertension and TPRI increase during administration of rHuEPO to increase the hematocrit and packed red blood cell volume in patients with chronic renal failure and anemia. Increased TPRI and hypertension associated with correction of uremic anemia vasodilation and the increased blood viscosity have been noted in earlier investigations with transfusions. The hypertension and elevated TPRI demonstrated during rHuEPO therapy in patients with progressive chronic renal failure associated with increased hematocrit, and the trends toward systolic and diastolic cardiac dysfunction are noted herein. These changes were associated with the combined increase of packed RBC mass and plasma volume in this study. The natural progressive course of worsening of renal function exhibited by these patients could have limited their ability to regulate plasma volume, making them vulnerable to volume-dependent hypertension and a significant preload adding to potential cardiac dysfunction in addition to the increased TPRI.

Anemia

Selective reduction of serotonin storage and ATP release in chronic renal failure patients platelets.

Hemorrhagic complications, as monitored by skin bleeding times, occur in a significant number of chronic renal failure (CRF) patients. The etiology of hemostatic defects in these patients is complex and ill defined. Our studies demonstrate, for the first time, that activated platelets, derived from CRF patients, release significantly (P less than .001) less ATP than controls while the percent of releasable serotonin (5HT), assumed to be co-stored with ATP, is unaltered. Analysis of the CRF-derived platelets reflects a selective acquired storage pool defect with significantly (P less than .001) reduced 5HT levels while their dense granule contents of ATP and ADP are normal. The comparison of ATP release from platelets derived from CRF patients whose bleeding times were less than 9 min to those with bleeding times of 9 min or greater was significantly different (P less than .02). This report demonstrates for the first time that there is a statistically significant correlation of ATP release and 5HT content to bleeding times (P less than .001). The perturbation of platelet 5HT uptake, 5HT dense granule content, and ATP release appears to result from newly described altered plasma factors, detected by our in vitro mixing studies. It is proposed that the reduced level of releasable platelet 5HT and ATP contributes to bleeding disorders commonly encountered in CRF patients.

Adenosine Diphosphate

Desmopressin-induced improvement in bleeding times in chronic renal failure patients correlates with platelet serotonin uptake and ATP release.

Hemostatic defects resulting in life-threatening hemorrhagic episodes are a common occurrence in the chronic renal failure patient. Hemorrhagic tendencies correlate best with laboratory tests of bleeding times. The identification of a specific hemostatic defect and its role in bleeding dyscrasias has yet to be elucidated. Our studies demonstrate that factor VIII coagulant activity and factor VIII related antigen (vWF:Ag) are normal or greatly elevated in uremic renal failure patients with greatly prolonged bleeding times. The multimeric state of the von Willebrand factor is also normal in these patients. The bleeding times were normalized in all 15 patients, 90 minutes post-infusion with desmopressin (DDAVP). No significant changes in factor VIII/vWF associated properties, blood cell counts, or coagulation factors were observed post-DDAVP treatment. However, a significant increase in platelet serotonin uptake (p less than .025) and ATP release (p less than .025) was detected after DDAVP treatment. These results indicate that DDAVP acts on the platelet membrane. This is further substantiated by the ability of DDAVP to block vasopressin-induced platelet aggregation in a dose- and time-dependent fashion. Perturbations in the movement and storage of serotonin and the release of adenosine 5'-triphosphate (ATP) in the platelets of uremic individuals are proposed to play a critical role in regulating bleeding times.

Adenosine Diphosphate

Mental rotation of the neuronal population vector.

A rhesus monkey was trained to move its arm in a direction that was perpendicular to and counterclockwise from the direction of a target light that changed in position from trial to trial. Solution of this problem was hypothesized to involve the creation and mental rotation of an imagined movement vector from the direction of the light to the direction of the movement. This hypothesis was tested directly by recording the activity of cells in the motor cortex during performance of the task and computing the neuronal population vector in successive time intervals during the reaction time. The population vector rotated gradually counterclockwise from the direction of the light to the direction of the movement at an average rate of 732 degrees per second. These results provide direct, neural evidence for the mental rotation hypothesis and indicate that the neuronal population vector is a useful tool for "reading out" and identifying cognitive operations of neuronal ensembles.

Animals

Cognitive spatial-motor processes. 3. Motor cortical prediction of movement direction during an instructed delay period.

We studied the activity of 123 cells in the arm area of the motor cortex of three rhesus monkeys while the animals performed a 2-dimensional (2-D) step-tracking task with or without a delay interposed between a directional cue and a movement triggering signal. Movements of equal amplitude were made in eight directions on a planar working surface, from a central point to targets located equidistantly on a circle. The appearance of the target served as the cue, and its dimming, after a variable period of time (0.5-3.2 s), as the "go" stimulus to trigger the movement to the target; in a separate task, the target light appeared dim and the monkey moved its hand towards it without waiting. Population histograms were constructed for each direction after the spike trains of single trials were aligned to the onset of the cue. A significant increase (3-4x) in the population activity was observed 80-120 ms following the cue onset; since the minimum delay was 500 ms and the average reaction time approximately 300 ms, this increase in population activity occurred at least 680-720 ms before the onset of movement. A directional analysis (Georgopoulos et al. 1983, 1984) of the changes in population activity revealed that the population vector during the delay period pointed in the direction of movement that was to be made later.

Evoked Potentials

Electrocardiographic and hemodynamic effects of intravenous cocaine in awake and anesthetized dogs.

Graded bolus and infusion doses of cocaine were given to 18 dogs, 6 under general anesthesia and 12 awake, to determine the range of hemodynamic and electrocardiographic effects. Blood pressure, electrocardiographic measurements, cocaine plasma levels, temperature, electrolytes, and arterial blood gases were measured before and after the initial bolus and/or infusion at 10 minutes and each 30 minutes up to a maximum of 180 minutes. At the end of the infusion, a single large intravenous terminal bolus of cocaine was given. The hemodynamic and electrocardiographic changes occurred by 10 minutes after the bolus and resolved by 30 minutes, independent of the infusion rate and dose. Only anesthetized dogs could tolerate the highest cocaine doses. Three ranges of bolus doses were given: the lowest range was the average initial bolus dose received by the awake group; the intermediate range was the average initial bolus dose received by the anesthetized group; and the highest range was the average terminal bolus dose. The heart rate changes were unpredictable and did not change significantly at any dose range. The blood pressure increased in the lowest dose range, remained unchanged at intermediate doses, and fell at the highest doses in four of six dogs. Electrocardiographic intervals increased as the dose range increased. Only at the highest doses did potentially lethal ventricular arrhythmia (ventricular tachycardia and an idioventricular escape rhythm) occur. Intravenous cocaine causes hemodynamic and electrocardiographic effects that are related to the dose and rate of administration. At high doses, hypotension, arrhythmia, and electrocardiographic changes consistent with infranodal and/or intraventricular conduction slowing can occur.

Anesthesia, General

Electrophysiologic effects of cocaine on the canine ventricle.

To evaluate the electrophysiologic effects of cocaine on the ventricle, 12 conscious dogs were studied before and after a bolus and infusion of cocaine titrated to maximum tolerance or to an increase in the mean blood pressure by at least 15%. Plasma cocaine levels, blood pressure, and surface and intracardiac electrograms were recorded. Programmed electrical stimulation was performed from the right ventricle at drive cycle lengths of 400 and 350 ms with introduction of up to three extrastimuli. The right ventricular effective refractory period decreased by 10% (p less than or equal to 0.01) and the mean blood pressure increased by 19% (p less than or equal to 0.01). No sustained spontaneous or induced ventricular arrhythmias were recorded after cocaine administration. There were no significant changes in pacing threshold, intraventricular conduction, heart rate, QRS or QTc intervals. The cocaine dose infused was 2.1 +/- 1.0 mg/kg; cocaine plasma levels were 1969 +/- 959 ng/ml immediately after the bolus and 508 +/- 234 ng/ml at the end of the study. It is concluded that in a presumably normal canine heart and at the doses given that cocaine decreases right ventricular effective refractory period, does not change intraventricular conduction, and does not result in sustained spontaneous or induced ventricular arrhythmias.

Animals

Lack of antibodies to Legionella pneumophila and Legionella micdadei in hemodialysis patients.

In 231 adult hemodialysis patients and 134 healthy adults, we measured antibodies to Legionella pneumophila (serogroups 1-6) and Legionella micdadei by indirect immunofluorescent antibody tests to assess the risk of Legionnaires' disease. One of the patients had a titer of 1:512 to Legionella pneumophila but he had no history of Legionnaires' disease. Two had a titer of 1:64 to Legionella pneumophila, and none had a titer of greater than or equal to 1:64 to Legionella micdadei. By contrast, none of the control group had a titer greater than or equal to 1:64 to Legionella pneumophila and two had a titer of 1:64 to Legionella micdadei. Thus, our population of maintenance hemodialysis patients did not display increased prevalence of antibodies of Legionella pneumophila and Legionella micdadei, but prospective studies of pneumonia in hemodialysis patients might further evaluate possible risk of Legionnaires' disease.

Adult

Contamination of perfused donor kidneys by starch from surgical gloves.

Starch induces a variety of inflammatory reactions in humans and may contaminate surgical procedures from surgical gloves. Using polarized microscopy and electron microscopy, the authors observed starch particles in renal perfusate and in glomeruli of perfused donor kidneys. Group 1 consisted of 10 unusable kidneys handled with standard concern of glove sterility. Eight other kidneys (Group 2) were perfused with particular attention toward avoidance of starch contamination. The gloves were rinsed five times, and the cuffs were not dipped into the perfusate. Two kidneys (Group 3), deemed unsuitable for transplantation, were perfused for 24 hours with perfusate swished with unwashed sterile gloves. Group 4 consisted of five transplant biopsies performed within one week after transplantation. Perfusates alone were also circulated through the Waters Perfusion Machine continuously for 24, 72, and 188 hours with and without the use of gloves. The number of birefringent crosses were counted in each of 25 glomeruli per specimen. Group 1 displayed a mean of 1.8 birefringent crosses per glomerulus; Group 2, 0; Group 3, 5.3; and Group 4, 4.4. Groups 1 and 3 also exhibited birefringent crosses in peripheral renal vessels. Perfusate alone, handled without gloves, showed no birefringent crosses; by contrast, perfusate handled with gloves showed numerous birefringent crosses. The authors conclude that starch from surgical gloves can enter the perfusate and lodge in glomeruli and other sites of donor kidneys. Rinsing gloves five times and avoiding contact of the perfusate with the glove cuff effectively eliminates the contamination.

Birefringence