Fluorescence spectroscopy guidance of laser ablation of atherosclerotic plague

Laser-induced fluorescence (LIF) spectroscopy can only be used for laser angioplasty guidance if high-power laser ablation does not significantly alter the pattern of tissue fluorescence. Although the spectra of normal and atherosclerotic arteries differ, the change in fluorescence spectra following laser angioplasty has not been well studied. Therefore, the purpose of this study was to assess whether laser-induced fluorescence spectroscopy could guide selective laser ablation of atherosclerotic plaque and, if so, to develop a quantitative LIF score that could be used to control a "smart" laser angioplasty system. Baseline LIF spectroscopy of 50 normal and 50 atherosclerotic human aortic specimens was performed using an optical fiber coupled to a He-Cd laser and optical multichannel analyzer. LIF was then serially recorded during erbium:YAG laser ablation of 27 atherosclerotic specimens. Laser ablation was terminated when the arterial LIF spectrum visually appeared normal. Histologic analysis revealed a mean initial plaque thickness of 1,228 +/- 54 microns and mean residual plaque thickness of 198 +/- 27 microns. Ablation of the media occurred in only three specimens. A discriminant function was derived to discriminate atherosclerotic from normal tissue for computer guidance of laser angioplasty. The LIF score, derived from stepwise multivariate linear regression analysis of the LIF spectra, correctly classified 93% of aortic specimens. The spectra obtained from the atherosclerotic specimens subjected to fluorescence-guided laser revealed a change in score from "atherosclerotic" to "normal" following plaque ablation. Seven atherosclerotic specimens were subjected to laser angioplasty with on-line computer control using the LIF score. Mean initial plaque thickness was 1,014 +/- 86 microns, and mean residual plaque thickness was 78 +/- 29 microns. There was no evidence of ablation of the media. Therefore, LIF guidance of laser ablation resulted in minimal residual plaque without arterial perforation. These findings support the feasibility of an LIF-guided laser angioplasty system for selective atherosclerotic plaque ablation.     

Modulation of cutaneous reflexes in arm muscles during walking: further evidence of similar control mechanisms for rhythmic human arm and leg movements

Stimulation of cutaneous nerves innervating the hand evokes prominent reflexes in many arm muscles during arm cycling. We hypothesized that the mechanisms controlling reflex modulation during the rhythmic arm swing of walking would be similar to that documented during arm cycling. Thus, we expected cutaneous reflexes to be modulated by position in the walking cycle (phase dependence) and be different when walking compared to contraction while standing (task dependence). Subjects performed static postures similar to those occurring during walking and also walked on a treadmill while the superficial radial nerve was electrically stimulated pseudorandomly throughout the step cycle. EMG was recorded bilaterally from upper limb muscles and kinematic recordings were obtained from the elbow and shoulder joints. Step cycle information was obtained from force-sensing insoles. Analysis was conducted after averaging contingent upon the occurrence of stimulation in the step cycle. Phase-dependent modulation of cutaneous reflexes at early (~50–80 ms) and middle (~80–120 ms) latencies was observed. Coordinated bilateral reflexes were seen in posterior deltoid and triceps brachii muscles. Task dependency was seen in that reflex amplitude was only correlated with background EMG during static contraction (75% of comparisons for both early and middle latency reflexes). During walking, no significant relationship between reflex amplitude and background EMG level was found. The results show that cutaneous reflex modulation during rhythmic upper limb movement is similar to that seen during arm cycling and to that observed in leg muscles during locomotion. These results add to the evidence that, during cyclical movements of the arms and legs, similar neural mechanisms observed only during movement (e.g. central pattern generators) control reflex output. Electronic Publication     

The effect of erroneous responses on response monitoring in patients with major depressive disorder: a study with event-related potentials

Perceived failure is reported to have detrimental effects on subsequent performance in patients with major depressive disorder. We investigated the error-related negativity (ERN)/error negativity (Ne), an electrophysiological correlate of response monitoring, using a 64-channel EEG. Sixteen patients with DSM-IV major depressive disorder and 16 matched controls participated in an Eriksen flanker task with continuous performance feedback that signaled monetary reward. Compared to controls, patients with major depressive disorder showed a less negative ERN/Ne in error trials following error trials. This result might reflect impaired response monitoring processes in major depressive disorder resulting from an underactivity in a central reward pathway and/or a deficit in strategic reasoning.     

Finger opening in an overarm throw is not triggered by proprioceptive feedback from elbow extension or wrist flexion

 Accuracy in an overarm throw requires great precision in the timing of finger opening. We tested the hypothesis that finger opening in an overarm throw is triggered by proprioceptive feedback from elbow extension or wrist flexion. The hypothesis was tested in two ways: first, by unexpectedly perturbing elbow extension or slowing wrist flexion and determining whether changes occurred in finger opening, and second, by measuring the latency from the start of these joint rotations to the start of finger opening. Subjects threw balls fast and accurately from a sitting or standing position while joint rotations were recorded with the search-coil technique. Elbow extension was unexpectedly blocked near the start of forward motion of the hand by a rope attached to the wrist that passed through a catch mechanism located behind the subject. In spite of a slowing or complete block of elbow extension, and in some cases a replacement of elbow extension by elbow flexion, finger opening always occurred and at the same latency as for normal throws. Wrist flexion was slowed in seven of eight subjects when subjects changed from throwing with a light ball (14 g, 70 mm diam.) to a heavy ball (210 g, 65 mm diam.). For the first throw with the heavy ball, this slowing was neither fully anticipated by the subject nor compensated for by the changed proprioceptive feedback associated with the slowing. Consequently, the timing of finger opening was unchanged and (to the surprise of the thrower) the ball went high. Furthermore, in unperturbed throws with tennis balls, the latency from onset of wrist flexion or elbow extension to onset of finger opening was too short for either to have triggered finger opening (across subjects means were 4 ms for wrist flexion and 21 ms for elbow extension). In additional analysis, no relation was found between the time of onset of earlier occurring rotations at the shoulder and the time of onset of finger opening. We concluded that, although a role for all proprioceptive feedback in triggering finger opening cannot be disproved by these experiments, it can be ruled out for feedback arising from elbow extension and wrist flexion, and it seems unlikely for feedback arising from events occurring very early in the throw. The more likely possibility is that finger opening in an overarm throw is triggered by a central command based on an internal model of hand trajectory. Received: 6 July 1998 / Accepted: 16 October 1998     

Renal nerve stimulation restores tubuloglomerular feedback after acute renal denervation

Renal nerves play an important role in the setting of the sensitivity of the tubuloglomerular feedback (TGF) mechanism. We recently reported a time-dependent resetting of TGF to a lower sensitivity 3–4 h after acute unilateral renal denervation (aDNX). This effect persisted after 1 week, but was then less pronounced. To determine whether normal TGF sensitivity could be restored in aDNX kidneys by low-frequency renal nerve stimulation (RNS), the following experiments were performed. Rats with aDNX were prepared for micropuncture. In one experimental group proximal tubular free flow (P_t) and stop flow pressures (P_sf) were measured during RNS at frequencies of 2, 4 and 6 Hz. In another series of experiments the TGF sensitivity was evaluated from the P_sf responses at different loop perfusion rates after 20 min of RNS at a frequency of 2 Hz. The maximal drop in P_sf (ΔP_sf) and the tubular flow rate at which half the maximal response in ΔP_sf was observed (turning point, TP), were recorded. At RNS frequencies of 2, 4 and 6 Hz, P_t decreased from the control level of 14.1 ± 0.8–13.1 ± 1.0, 12.4 ± 1.1 and 11.2 ± 0.8 mmHg (decrease 21%, P < 0.05), respectively, while at zero perfusion and during RNS at 2 and 4 Hz P_sf decreased from 42.5 ± 1.6 to 38.2 ± 1.4 and 32.8 ± 4.3 mmHg (decrease 23%, P < 0.05), respectively. The TGF characteristics were found to be reset from the normal sensitivity with TP of 19.0 ± 1.1 nL min^–1 and ΔP_sf of 8.7 ± 0.9 mmHg to TP of 28.3 ± 2.4 nL min^–1 (increase 49%, P < 0.05) and ΔP_sf of 5.8 ± 1.2 mmHg (decrease 33%) after aDNX. After 20 min of RNS at 2 Hz TP was normalized and ΔP_sf was 33% higher. Thus the present findings indicate that the resetting of the TGF sensitivity that occurred 2–3 h after aDNX could be partially restored by 20 min of RNS at a frequency of 2 Hz. These results imply that renal nerves have an important impact on the setting of the sensitivity of the TGF mechanism.     

The interaction of conflicting retinal motion stimuli in oculomotor control

Summary Oculomotor response has been assessed in humans during the presentation of conflicting retinal motion stimuli. In the majority of experiments a background stimulus was made to move with a constant velocity ramp in one direction followed by rapid resets at regular intervals. In the absence of an adequate fixation target this ramp-reset stimulus induced a nystagmus with a slow-phase velocity and saccadic frequency which remained almost constant as reset frequency was increased from 2 to 5 Hz. Moreover, the induced eye velocity could be considerably increased if the subject attempted active matching of display velocity. During both active and passive responses eye velocity gain reached a peak when display velocity was between 2°/s and 5°/s. The presence of small stationary targets induced a suppression of the passive ramp-reset response which was modified by target eccentricity and by tachistoscopic target illumination. When subjects pursued a sinusoidally oscillating target against a stationary structured background, eye velocity gain was significantly less than for pursuit against a blank background. The degree of interaction between conflicting stimuli was found to be dependent on their relative size, peripheral location and velocity. However, it appears that the human observer is able selectively to enhance feedback gain from one particular source in order to dominate stimuli from other unwanted sources.     

The role of visual feedback of hand position in the control of manual prehension

 Although it is obvious that vision plays a primary role in reaching and grasping objects, the sources of the visual information used in programming and controlling various aspects of these movements is still being investigated. One source of visual information is feedback relating to the characteristics of the reach itself – for example, the speed and trajectory of the moving limb and the change in the posture of the hand and fingers. The present study selectively eliminated this source of visual information by blocking the subject’s view of the reaching limb with an opaque barrier while still enabling subjects to view the goal object. Thus, a direct comparison was made between standard (closed-loop) and object-only (open-loop) visual-feedback conditions in a situation in which the light levels and contrast between an object and its surroundings were equivalent in both viewing conditions. Reach duration was longer with proportionate increases in both the acceleration and deceleration phases when visual feedback of the reaching limb was prevented. Maximum grip aperture and the proportion of movement time at which it occurred were the same in both conditions. Thus, in contrast to previous studies that did not employ constant light levels across closed- and open-loop reaching conditions, a dissociation was found between the spatial and temporal dimensions of grip formation. It appears that the posture of the hand can be programmed without visual feedback of the hand – presumably via a combination of visual information about the goal object and proprioceptive feedback (and/or efference copy). Nevertheless, maximum grip aperture (like the kinematic markers examined in the transport component) was also delayed when visual feedback of the reaching limb was selectively prevented. In other words, the relative timing of kinematic events was essentially unchanged, reflecting perhaps a tight coupling between the transport and grip components. Received: 3 July 1998 / Accepted: 18 November 1998     

Heterogeniety in regulation of glomerular function

The aim was to study differences in filtration driving forces and glomerular filtration rates between superficial and deep nephrons when urine flow rate was altered at the macula densa region. In young rats stop-flow pressures and single nephron glomerular filtration rates (SNGFR) were measured in the superficial proximal tubules and in the loops of Henle in the papilla. SNGFR was also measured with a modified Hanssen technique. The stop-flow pressures of superficial nephrons amounted to 30.9±0.8 mmHg (mean ± SE) and those of juxtamedullary nephrons to 52.2±1.6 mmHg. In the stop-flow condition the net driving filtration forces were calculated to be about 19 mmHg and 50 mmHg for the superficial and deep glomeruli, respectively. In free flow conditions both net driving forces were calculated to be 19 mmHg. The micropuncture technique gave a SNGFR value for superficial nephrons of 29.6±2.9 and for deep nephrons of 84.1±8.5 nl±min^-1 g^-1 kidney weight (KW). With a modified Hanssen technique the corresponding values were 25.8±3.3 and 27.7±2.9 nl. min^-1.g^-1KW. The tubuloglomerular feedback mechanism is considered to have a powerful regulatory influence on the glomerular filtration rate of deep nephrons.     

Continuous Biofeedback and Discrete Posttrial Verbal Feedback in Frontalis Muscle Relaxation Training

During training to relax the frontalis muscle, continuous biofeedback (BF) was compared to discrete verbal feedback (VF) delivered immediately after each trial. Both feedback modalities were based on frontalis electromyographic (EMG) activity. Training consisted of 3 consecutive daily session-each comprised of 3 baseline (nonfeedback) trials followed by 10 training trials of 128 see. The presence or absence of the two informationally positive feedback modalities were combined factorially to define four training conditions: BF + VF, NO BF + VF, BF + NO VF, and NO BF + NO VF. Results indicated that while VF alone facilitated muscle relaxation, BF was clearly prepotent ill effecting consistent decreases in EMG activity both across trials and days of training. Additionally, the facilitating effect of BF transferred to nonfeedback trials while VF did not affect performance on nonfeedback trials. Finally, accuracy of self-evaluations of performance on a trial by trial basis was markedly improved by BF, while VF improved accuracy only for trials having a very large absolute difference between levels of EMG activity. Ss receiving no feedback neither reduced muscle tension during training not were able to evaluate their performance accurately even when large absolute differences occurred between trials in frontalis EMG activity.     

Simple mechanical-chemical systemic pressure-control device

An implantable mechanical-chemical device was constructed to act as a feedback mechanism in controlling the blood pressure. It consisted of a balloon connected to a rubber catheter ending in a slit valve. Flow-pressure curves were derived fromin vitro testings for three valve thresholds (120, 140 and 170 mmHg). Five fast-acting hypotensive drugs subsequently filled the device during 40 noradrenaline infusions in 25 dogs, with the balloon in the abdominal aorta and the catheter in the inferior vena cava. The results were as follows: (i) Following a short initial increase in systolic aortic pressure, significantly lower (p<0·001) than in control experiments, the device prevented any pressure rise above its threshold. (ii) The time needed for pressure lowering at the device's threshold depended on the drug used being 3·34±0·84 (mean ± s.e. in minutes) for sodium nitroprusside, 5·99±0·96 for phentolamin, 11·63±2·97 for hydralazine, 14·54±2·43 for a-methyl-dopa and 23·32±2·07 for diazoxide.