Rostral ventrolateral medullary and caudal medullary raphe neurons with activity correlated to the 10-Hz rhythm in sympathetic nerve discharge.

1. The current study is the first to identify medullary neurons whose naturally occurring discharges were correlated to the 10-Hz rhythm in sympathetic nerve discharge (SND). Spike-triggered averaging showed that 44 of 164 rostral ventrolateral medullary (RVLM) and 44 of 174 caudal medullary raphe neurons had activity correlated to the 10-Hz rhythm in inferior cardiac postganglionic SND of 23 baroreceptor-denervated, decerebrate cats. 2. When the frequency of the rhythm in SND was decreased by lowering body temperature, the discharges of the 10 neurons tested (6 RVLM and 4 raphe) remained locked to the peak of the next 10-Hz sympathetic nerve slow wave rather than to the peak of the preceding slow wave. This observation supports the contention that the 10-Hz rhythm in basal SND was generated in the brain stem rather than in the spinal cord. 3. Frequency-domain analysis was used to characterize further the relationship between the 10-Hz rhythm in SND and the discharges of 30 RVLM and 24 raphe neurons. The autospectra of the discharges of eight RVLM and four raphe neurons contained a sharp peak near 10 Hz, although the mean firing rates of these neurons were lower than the frequency of the rhythm in SND. Coherence values as high as 0.76 characterized the relationship between the discharges of these "rhythmically firing neurons" and the 10-Hz rhythm in SND. A coherence value of 1.0 indicates a perfect correlation. The autospectra of the discharges of the 22 RVLM and 20 raphe neurons did not contain a peak near 10 Hz. The mean firing rates and coherence values relating the discharges of these "nonrhythmically firing neurons" and the 10-Hz rhythm in SND were significantly lower than those for the rhythmically firing neurons. Because the frequency of the population rhythm recorded from the inferior cardiac nerve was higher than the firing rates of individual medullary neurons, the 10-Hz rhythm in SND appears to be an emergent property of a network of neurons whose discharges are probabilistically related to the population rhythm. 4. In addition to the peak near 10-Hz, the autospectrum of SND often contained considerable power at frequencies < 6 Hz. This component of SND is called the 2- to 6-Hz rhythm.(ABSTRACT TRUNCATED AT 400 WORDS)


Oscillatory discharge in the visual system: does it have a functional role?

1. The discharge of individual neurons in the visual cortex and lateral geniculate nucleus (LGN) of anesthetized and paralyzed cats and kittens was examined for the presence of oscillatory activity. Neural firing was evoked through the monoptic or dichoptic presentation of drifting gratings and random sequences of flashed bars. The degree to which different oscillatory frequencies were present in neural discharge was quantified by computation of the power spectra of impulse train responses. 2. Action potentials from single cells were recorded extracellularly and isolated on the basis of amplitude. Receptive-field properties of the neurons under study were characterized initially by their discharge in response to gratings of sinusoidal luminance. By varying orientation and spatial frequency, optimal stimulus characteristics were determined. Oscillation analysis was performed on spike trains acquired during repeated presentations of the optimal stimulus by identification of power spectra peaks in the frequency range of rhythmic potentials observed in electroencephalograph studies (30-80 Hz). The amplitude and frequency of the largest peak in this range was used to characterize oscillatory strength and frequency. All discharge in which the peak amplitude exceeded the high-frequency noise by a factor > 1.5 was classified as oscillatory. 3. Of the 342 cortical cells examined, 147 cells displayed oscillatory activity in the 30 to 80-Hz range during portions of their visual response. Sixty out of 169 simple cells, 82 out of 166 complex cells, and 5 out of 7 special complex cells exhibited oscillations. There was no laminar bias in the distribution of oscillatory cells; the proportions of oscillatory cells were similar in all layers. All oscillatory discharge was variable with respect to frequency and strength between successive presentations of the same optimal stimulus. In as little as 10 s, for example, peak frequencies shifted by a factor of two. For many cells, these trial-to-trial variations obscured detectable oscillations when all trials were averaged together. 4. The potential role of neuronal maturation in the generation of oscillatory activity was investigated by studying neuronal responses from kittens at 4 wk postnatal. Of the 80 kitten cells studied, 27 exhibited oscillatory discharge. Although oscillations in the kitten visual cortex spanned the same frequency range as that seen in the adult, oscillations in the midfrequency range (36-44 Hz) are more common in the adult cortex. 5. To explore the possibility that oscillations might play a functional role in vision, we investigated the dependence of oscillations on different stimulus parameters.(ABSTRACT TRUNCATED AT 400 WORDS)


Segmental organization of visceral and somatic input onto C3-T6 spinothalamic tract cells of the monkey.

1. Referred pain of visceral origin has three major characteristics: visceral pain is referred to somatic areas that are innervated from the same spinal segments as the diseased organ; visceral pain is referred to proximal body regions and not to distal body areas; and visceral pain is felt as deep pain and not as cutaneous pain. The neurophysiological basis for these phenomena is poorly understood. The purpose of this study was to examine the organization of viscerosomatic response characteristics of spinothalamic tract (STT) neurons in the rostral spinal cord. Interactions were determined among the following: 1) segmental location, 2) effects of input by cardiopulmonary sympathetic, greater splanchnic, lumbar sympathetic, and urinary bladder afferent fibers, 3) location of excitatory somatic field, e.g., hand, forearm, proximal arm, or chest, 4) magnitude of response to hair, skin, and deep mechanoreceptor afferent input, and 5) regional specificity of thalamic projection sites. 2. A total of 89 STT neurons in segments C3-T6 were characterized for responses to visceral and somatic stimuli. Neurons were activated antidromically from the contralateral ventroposterolateral oralis or caudalis nuclei of the thalamus. Cell responses to visceral and somatic stimuli were not different on the basis of the thalamic site of antidromic activation. Recording sites for 61 neurons were located histologically; 87% of lesion sites were located in laminae IV-VII or X. There was no relationship between response properties of the neurons and spinal laminar location. 3. Different responses to visceral stimuli were observed in three zones of the rostral spinal cord: C3-C6, C7-C8, and T1-T6. In C3-C6, urinary bladder distension (UBD) and electrical stimulation of greater splanchnic and lumbar sympathetic afferent fibers inhibited STT cells. Electrical stimulation of cardiopulmonary sympathetic afferents increased cell activity in C5 and C6 and either excited or inhibited STT cells in C3 and C4. In the cervical enlargement (C7-C8), STT cells generally were either inhibited or showed little response to stimulation of visceral afferent fibers. In T1-T6, input from greater splanchnic and cardiopulmonary sympathetic afferent nerves increased activity of STT cells. Lumbar sympathetic afferent input inhibited cells in T1-T2 and had little effect on cells in T3-T6, whereas UBD decreased cell activity in all segments studied. 4. In general, stimulation of somatic structures increased activity of STT neurons in segments that received primary afferent innervation from the excitatory somatic receptive field or in the segments immediately adjacent to these segments. Only input from the forelimb, especially the hand, markedly excited cells in C7 and C8.+


Dynamic range of neural rate responses in the ventral cochlear nucleus of awake cats.

1. Response thresholds and dynamic range properties of neurons in the ventral cochlear nucleus (VCN) of awake cats were measured by fitting a computational model to rate-level functions for best frequency (BF) tone bursts and for bursts of broad-band noise. Dynamic range measurements were performed in quiet and in the presence of continuous background noise. 2. The sample of neurons obtained in the VCN of awake cats exhibited a variety of peristimulus histograms (PSTHs) and thresholds. All PSTH response types previously described in the VCN of anesthetized cats were found in awake cats. The lowest thresholds for neural responses were observed at sound pressure levels that were equivalent to behavioral thresholds of absolute auditory sensitivity. 3. When responses to BF tones or bursts of broad-band noise were recorded in quiet backgrounds, the dynamic range properties of most units in the VCN of awake cats were not significantly different from dynamic range properties of auditory nerve fibers (ANFs) in anesthetized cats or VCN units in decerebrate cats. All auditory units showed a larger dynamic range for noise bursts than for tone bursts, but VCN units with primary-like and onset PSTHs showed larger dynamic ranges for responses to noise bursts than that of ANFs and VCN chopper units. 4. When tests were performed in the presence of continuous noise, rate-level functions for BF tone bursts shifted to higher tone levels and showed a more compressed range of driven rates in comparison with data obtained in quiet. Compression of the rate-level function in noise resulted from an increase in driven rate at low tone levels and a decrease in rate at high tone levels. These changes in the rate-level function suggest that noise may reduce the range of BF tone levels that are potentially encoded by a unit's rate responses. By exhibiting larger shifts and less compression in background noise, VCN units in awake cats better preserved the dynamic range of their rate responses to BF tones than ANFs in anesthetized cats or VCN units in decerebrate cats. 5. Rate-level functions were obtained from a small sample of VCN units not only with the cat performing the behavioral task but also with the cat awake and sitting quietly in the testing apparatus. No differences in noise-induced shift or compression were noted between the two testing conditions.(ABSTRACT TRUNCATED AT 400 WORDS)


Activity-dependent potentiation and depression of visual cortical responses to optic nerve stimulation in kittens.

1. To see whether long-lasting changes in synaptic efficacy are induced in the developing visual cortex (VC), field potentials evoked by test stimulation given alternatively to each of the optic nerves (ONs) were recorded from VC of kittens ranging in age from 4 to 8 wk. In some experiments, field potentials were recorded simultaneously from the dorsal lateral geniculate nucleus (LGN) in addition to VC. 2. Tetanic stimulation was applied to one of the ONs for 1-60 min at 5 Hz. Homosynaptic potentiation of cortical responses, defined as an increase lasting > 2.5 h in the cortical field potential evoked by test stimulation of the ON that was tetanized, was induced without any changes in LGN responses in 3 of the 12 kittens tested. Heterosynaptic depression, defined as a decrease lasting > 0.5 h in the field potential evoked by stimulation of the ON that was not tetanized, was also induced in two of those three kittens. 3. To elucidate a role of inputs originating from spontaneous activity of retinal ganglion cells in induction of potentiation and depression in the cortex, tetrodotoxin (TTX) was injected into both eyes of 11 kittens. After we confirmed the suppression of retinal activity by TTX, tetanic stimulation was applied to ON. Homosynaptic potentiation of cortical responses was induced in 6 of the 11 kittens, and the ratio of the mean amplitude of posttetanic responses to that of pretetanic responses for the 11 kittens was on average larger than that for the 12 control kittens. Heterosynaptic depression was not observed in any of the 11 kittens. 4. To see a role of postsynaptic activity in induction of potentiation and depression, gamma-aminobutyric acid (GABA) was applied continuously to the VC by an infusion pump in 10 kittens. Tetanic stimulation was given to ON while cortical activities were suppressed by GABA. After recovery of cortical activities, homosynaptic depression was found to be induced in 3 of the 10 kittens, but homosynaptic potentiation was not observed at all. The ratio of amplitude of posttetanic to pretetanic responses at the tetanized side for the 10 kittens was on average smaller than that for the 11 TTX-injected kittens. 5. These results can be accounted for by the modified covariance model in which the relation of postsynaptic activity and direction of changes in synaptic efficacy is formulated.(ABSTRACT TRUNCATED AT 400 WORDS)


Inactivation of the DSCF area of the auditory cortex with muscimol disrupts frequency discrimination in the mustached bat.

1. The Jamaican mustached bat uses a biosonar signal (pulse) with eight major components: four harmonics each consisting of a long constant frequency (CF1-4) component followed by a short frequency-modulated (FM1-4) component. While flying, the bat adjusts the frequency of its pulse so as to maintain the CF2 of the Doppler-shifted echo at a frequency to which its cochlea is very sharply tuned. This Doppler shift (DS) compensation likely is mediated or influenced by the Doppler-shifted CF (DSCF) processing area of the primary auditory cortex, which only represents frequencies in the range of echo CF2s (60.6 to 62.3 kHz when the "resting" frequency of the CF2 is 61.0 kHz). 2. We trained four bats to discriminate between different trains of paired tone bursts that mimicked a bat's pulse CF2 and the accompanying echo CF2. The frequency of these CF2s ranged between 61.0 and 64.0 kHz. A discriminated shock avoidance procedure response was employed using a leg flexion. For one stimulus, the S+, the pulse and echo CF2s were the same frequency (delta f = 0, i.e., no Doppler shift). A leg flexion during the S+ turned off both the S+ and the scheduled shock. For a second stimulus, the S-, the echo CF2 was 0.05, 0.1, 0.3, 0.5, or 2.0 kHz higher than the pulse CF2. A delta f of 0.05 kHz was a frequency difference of 0.08%. No shock followed the S-, and leg flexions had no consequences. Correct responses consisted of a leg flexion during the S+ and no flexion during the S-; these responses were added together to compute the percentage of correct responses. When a bat correctly responded at better than 75% for all the delta f s, muscimol, a potent agonist of gamma-aminobutyric acid, was bilaterally applied to inactivate the DSCF area. Performance on each delta f discrimination was then measured. 3. Initial attempts to condition the bats to flex their legs to the CF tones mimicking part of the natural pulses and echoes failed. When broad-band noise bursts were substituted, however, the conditioned response was rapidly established. The noise band-width was gradually reduced and then replaced with the CF tones. Discrimination training with the tone burst trains then commenced. Throughout this procedure, the bats maintained their responding to the stimuli. The bats typically required approximately 20-30 sessions to perform consistently (> or = 75% correct responses) a discrimination involving a 2 kHz delta f.(ABSTRACT TRUNCATED AT 400 WORDS)


Saccade-vergence interactions in humans.

1. We recorded eye movements in four normal human subjects during refixations between targets calling for various combinations of saccades and vergence. We confirmed and extended prior observations of 1) transient changes in horizontal ocular alignment during both pure horizontal saccades (relative divergence followed by relative convergence) and pure vertical saccades (usually divergence for upward and convergence for downward saccades); 2) occasional, high-frequency (20-25 Hz), conjugate oscillations along the axis orthogonal to the main saccade; and 3) the speeding up of horizontal vergence by both horizontal and vertical saccades. 2. To interpret these findings, we developed a hypothesis for the generation of vergence to step changes in target depth, both with and without associated saccades. The essential features of this hypothesis are 1) the transient changes in horizontal ocular alignment during pure horizontal saccades reflect asymmetries in the mechanical properties of the lateral and medial rectus muscles causing adduction to lag abduction; 2) pure vergence movements in response to step changes in target depth are generated by a neural network that uses a desired change in vergence position as its input command and instantaneous vergence motor error (the difference between the desired change and the actual change in vergence) to drive vergence premoter neurons; and 3) the facilitation of horizontal vergence by saccades arises from nonlinear interactions in central premotor circuits. 3. The hypothetical network for generating pure vergence to step changes in target depth is analogous in structure to the local feedback model for the generation of saccades and has the same conceptual appeal. With the assumption of a single nonlinearity describing the relationship between a vergence motor error signal and the output of the neurons that generate promoter vergence velocity commands, this model generates pure vergence movements with peak velocity-amplitude relationships and trajectories that closely match those of experimental data. 4. Several types of models are proposed for the central, nonlinear interaction that occurs when saccades and vergence are combined. Common to all models is the idea that omnidirectional pause neurons (OPN), which are thought to gate activity for saccade burst neurons, also gate activity for saccade-related vergence. In one model we hypothesize the existence of a separate class of saccade-related vergence burst neurons, which generate premotor horizontal vergence commands but only during saccades. In a second model we hypothesize separate right eye and left eye saccadic burst neurons that receive not only conjugate, but also equal but oppositely directed vergence error signals.(ABSTRACT TRUNCATED AT 400 WORDS)


Orthopteran DCMD neuron: a reevaluation of responses to moving objects. I. Selective responses to approaching objects.

1. The "descending contralateral movement detector" (DCMD) neuron in the locust has been challenged with a variety of moving stimuli, including scenes from a film (Star Wars), moving disks, and images generated by computer. The neuron responds well to any rapid movement. For a dark object moving along a straight path at a uniform velocity, the DCMD gives the strongest response when the object travels directly toward the eye, and the weakest when the object travels away from the eye. Instead of expressing selectivity for movements of small rather than large objects, the DCMD responds preferentially to approaching objects. 2. The neuron shows a clear selectivity for approach over recession for a variety of sizes and velocities of movement both of real objects and in simulated movements. When a disk that subtends > or = 5 degrees at the eye approaches the eye, there are two peaks in spike rate: one immediately after the start of movement; and a second that builds up during the approach. When a disk recedes from the eye, there is a single peak in response as the movement starts. There is a good correlation between spike rate and angular acceleration of the edges of the image over the eye. 3. When an object approaches from a distance sufficient for it to subtend less than one interommatidial angle at the start of its approach, there is a single peak in response. The DCMD tracks the approach, and, if the object moves at 1 m/s or faster, the spike rate increases throughout the duration of object movement. The size of the response depends on the speed of approach. 4. It is unlikely that the DCMD encodes the time to collision accurately, because the response depends on the size as well as the velocity of an approaching object. 5. Wide-field movements suppress the response to an approaching object. The suppression varies with the temporal frequency of the background pattern. 6. Over a wide range of contrasts of object against background, the DCMD gives a stronger response to approaching than to receding objects. For low contrasts, the selectivity is greater for objects that are darker than the background than for objects that are lighter.


Orthopteran DCMD neuron: a reevaluation of responses to moving objects. II. Critical cues for detecting approaching objects.

1. We examine the critical image cues that are used by the locust visual system for the descending contralateral motion detector (DCMD) neuron to distinguish approaching from receding objects. Images were controlled by computer and presented on an electrostatic monitor. 2. Changes in overall luminance elicited much smaller and briefer responses from the DCMD than objects that appeared to approach the eye. Although a decrease in overall luminance might boost the response to an approaching dark object, movement of edges of the image is more important. 3. When two pairs of lines, in a cross-hairs configuration, were moved apart and then together again, the DCMD showed no preference for divergence compared with convergence of edges. A directional response was obtained by either making the lines increase in extent during divergence and decrease in extent during convergence; or by continually increasing the velocity of line movement during divergence and decreasing velocity during convergence. 4. The DCMD consistently gave a larger response to growing than to shrinking solid rectangular images. An increase compared with a decrease in the extent of edge in an image is, therefore, an important cue for the directionality of the response. For single moving edges of fixed extent, the neuron gave the largest response to edges that subtended 15 degrees at the eye. 5. The DCMD was very sensitive to the amount by which an edge traveled between frames on the display screen, with the largest responses generated by 2.5 degrees of travel. This implies that the neurons in the optic lobe that drive this movement-detecting system have receptive fields of about the same extent as a single ommatidium. 6. For edges moving up to 250 degree/s, the excitation of the DCMD increases with velocity. The response to an edge moving at a constant velocity adapts rapidly, in a manner that depends on velocity. Movement over one part of the retina can adapt the subsequent response to movement over another part of the retina. 7. For the DCMD to track and continue to respond to the image of an approaching object, the edges of the image must continually increase in velocity. This is the second important stimulus cue. 8. Edges of opposite contrasts (light-dark compared with dark-light) are processed in separate pathways that inhibit each other. This would contribute to the reduction of responses to wide-field movements.


Analysis and modeling of the multisegmental coordination of shortening behavior in the medicinal leech. I. Motor output pattern.

1. To understand how a multisegmental animal coordinates motor activity over more than one segment, we studied shortening behavior in the medicinal leech, in which several segments contract longitudinally in response to a moderately strong mechanical stimulus. 2. We first demonstrated that the neuronal activity responsible for shortening behavior occurred in semi-intact and isolated nerve cord preparations, and then characterized the responses of motor neurons in isolated preparations. The motor output during shortening was simultaneous excitation of motor neurons innervating dorsal longitudinal muscle and of motor neurons innervating ventral longitudinal muscle. 3. The stronger the stimulus, the more segments produced the shortening motor output, with the segments nearest the stimulus recruited first. 4. Although the shortening response was produced in several segments near the site of stimulation, it was never produced in the stimulated segment, where the local bending motor output pattern was produced. The motor pattern suggests that shortening, initially considered a very simple behavior, requires the involvement of at least few segmentally iterated interneurons.


Analysis and modeling of the multisegmental coordination of shortening behavior in the medicinal leech. II. Role of identified interneurons.

1. Mechanical stimulation of the leech, Hirudo medicinalis, elicits withdrawal behavior that has two components: local bending in the segment stimulated and shortening in outlying segments. Local bending is characterized by excitation of longitudinal muscle on one side of the segment and inhibition on the other side. In shortening, all longitudinal muscles are excited. We wished to understand how these distinct motor patterns are produced by a nervous system with segmentally iterated neurons, a configuration that places some limitations on the complexity of connection patterns. 2. We searched for neurons in the segmental nervous system that subserved shortening behavior, expecting to find at least one interneuron in each segment that was involved in shortening behavior exclusively. We found instead that all interneurons involved in shortening are also involved in local bending, and no individual interneuron can completely account for shortening. 3. The motor output caused by individual identified interneurons is not entirely consistent with the shortening motor output pattern. For instance, one interneuron, cell 115, has the same pattern of motor effects from segment to segment, causing excitation of dorsal excitatory motor neurons and inhibition of ventral excitatory motor neurons. These effects would cause dorsal local bending, not shortening, in a few segments. Only one interneuron, cell 125, has motor effects that would cause shortening. 4. Individual interneurons were hyperpolarized while single sensory cells were stimulated, to quantify the contributions of individual interneurons to the observed motor pattern. Interneurons 115 and 125, and the inhibitory motor neuron, cell 1, were found to have significant roles in producing the shortening motor output. 5. A quantitative estimate of the role of each interneuron type showed that the identified interneurons account for most of the excitation of dorsal motor neurons, but for very little of the excitation of ventral motor neurons. This predicts that at least one additional interneuron type remains to be identified, one that would provide excitation to ventral motor neurons in several segments. 6. A back-propagation trained neural network model was constructed to predict the connections of the as yet unidentified interneurons. To match the known properties of interneurons, it was necessary to include a segmental similarity constraint in the training algorithm for segmentally iterated model neurons. The modeled networks predicted that there are at least two kinds of interneurons yet to be found. Also, the modeling showed that interneurons can have input and output patterns that differ very little from segment to segment but yet produce major differences in the motor output.


Transient K current in the somatic membrane of cultured central neurons of embryonic rat.

1. Somatic K currents of cultured hippocampal, striatal, and spinal cord neurons of embryonic rat were recorded under voltage clamp in membrane spheres ("blebs") excised by means of a tight-seal pipette. 2. The somatic K current in blebs was subject to rapid and near complete inactivation during 300-ms depolarizations, whereas whole-cell K currents included a substantial maintained component. Size and kinetic properties of bleb and whole-cell currents were stable throughout the recording period. 3. The steady-state inactivation of somatic A current was steeply voltage dependent and complete near voltage levels that activated current, whereas peak conductances did not saturate during depolarizations up to +90 mV. Activation started with a delay. Half-times of activation decreased with depolarization, but half-times of inactivation varied little with depolarization. Recovery from inactivation followed a sigmoidal time course with half-times of approximately 50 ms. 4. Half-times of activation and inactivation varied over more than an order of magnitude between individual neurons. Midpoint potentials of inactivation and peak conductance varied over approximately 40 mV. The parameter ranges of hippocampal, striatal, and spinal cord neurons overlapped. 5. Individual soma membranes revealed signs of K channel heterogeneity in their 4-aminopyridine block, current fluctuations, and current kinetics. On the other hand, currents elicited after conditioning pulses that established varied degrees of steady-state inactivation or of recovery from full inactivation had superimposable time courses. 6. The described characteristics of the somatic A channels are compared with those reported for the RCK4, Raw3, and mShal products expressed in Xenopus oocytes. Whereas the ranges of voltage dependencies and of most kinetic characteristics are compatible among native and cloned channels, these three cloned channels recover much more slowly from inactivation. In addition, inactivation in native channels, unlike that in RCK4 and Raw3 channels, was stable after excision in a subcellular fragment.


Nociceptive neurons in area 24 of rabbit cingulate cortex.

1. Single-unit responses in area 24 of cingulate cortex were examined in halothane-anesthetized rabbits during stimulation of the skin with transcutaneous electrical (TCES, 3-10 mA), mechanical (smooth or serrated forceps to the dorsal body surface or graded pressures of 100-1,500 g to the stabilized ear) and thermal (> 25 degrees C) stimulation. 2. Of 542 units tested in cingulate cortex, 150 responded to noxious TCES (> or = 6 mA), 93 of 221 units tested responded to noxious mechanical (serrated forceps) and 9 of 47 units tested responded to noxious heat (> 43 degrees C) stimuli. Twenty-five percent of the units that responded to noxious mechanical stimuli also responded to noxious heat stimuli. The only innocuous stimulus that evoked activity in cingulate cortex was a "tap" to the skin and this was effective for 11 of 14 tested units. 3. In 74 units that produced excitatory responses to TCES of the contralateral ear, response latency was 166 +/- 11.3 (SE) ms and response duration was 519 +/- 52.1 ms. 4. Twenty of the 150 units that responded to noxious TCES were initially inhibited. These responses were usually < 1 s in duration (17 of 20 units), whereas responses in the other 3 lasted for over 20 s. 5. Most units had broad receptive fields, because noxious mechanical stimuli anywhere on the dorsal surface of the rabbits, including the face and ears, evoked responses. A small number of units for which the entire body surface was tested (3 of 15 units) had receptive fields limited to the ears, rostral back, and forepaws. 6. Fifteen of 33 units tested had no preferential responses to noxious TCES of the ipsilateral and contralateral ears. Of the remaining units, 10 had a greater response to contralateral and 8 had a greater response to ipsilateral stimuli. 7. The locations of 186 units were histologically verified. Most nociceptive cingulate units were in dorsal area 24b in layers III (n = 35), II (n = 13), or V (n = 9). 8. Cortical knifecut lesions were made in five rabbits to determine if the responses in area 24 were dependent on lateral or posterior cortical inputs. These lesions did not alter the percentage of units driven by noxious stimuli nor response latency. 9. Injections of lidocaine were made into medial parts of the thalamus in six animals and injection and recording sites analyzed histologically.(ABSTRACT TRUNCATED AT 400 WORDS)


Mechanisms underlying excitatory effects of thyrotropin-releasing hormone on rat hypoglossal motoneurons in vitro.

1. The hypoglossal motor nucleus contains binding sites for the neuropeptide thyrotropin-releasing hormone (TRH) and is innervated by TRH-containing fibers. Although excitatory effects of TRH on hypoglossal motoneurons (HMs) have been described, the ionic mechanisms by which TRH exerts such effects have not been fully elucidated. Therefore, we investigated the effects of TRH on HMs in transverse slices of rat brainstem with intracellular recording techniques. 2. TRH was applied by perfusion (0.1-10 microM) or by pressure ejection (1.0 microM), while HMs were recorded in current or voltage clamp. In all cells tested, TRH caused a depolarization and/or the development of an inward current. These effects were fully reversible, dose dependent, and showed only modest desensitization with long applications. In addition, although TRH increased synaptic activity in many cells, the depolarizing response to TRH was maintained in tetrodotoxin (0.5-1.0 microM)-containing or in a nominally Ca(2+)-free perfusate containing 2 mM Mn2+. Thus TRH acts directly on HMs to cause the depolarization. 3. Hyperpolarizing current (or voltage) steps superimposed on the TRH-induced depolarization (or inward current) revealed a decreased input conductance. Extrapolated instantaneous current-voltage relationships obtained before and at the peak of the response to TRH intersected (i.e., reversed) at -101 mV, negative to the expected K+ equilibrium potential (EK). When extracellular [K+] was raised from 3 to 12 mM, the reversal potential was shifted in the depolarizing direction and the magnitude of the TRH-induced depolarization was diminished. Moreover, the TRH response was enhanced in size from depolarized potentials (i.e., further from EK). Taken together, these results indicate that TRH depolarizes HMs, in part, by decreasing a resting K+ conductance. 4. Similar to TRH, bath-application of 2 mM Ba2+ caused a depolarization associated with decreased conductance, suggesting that Ba2+ also blocks a resting K+ conductance. The Ba(2+)-sensitive and TRH-sensitive resting K+ conductances are apparently identical; in the presence of Ba2+, the customary TRH-induced decrease in conductance was occluded. 5. It is noteworthy that the TRH-induced inward current (ITRH), although diminished, was not entirely blocked by Ba2+. This second Ba(2+)-insensitive component of ITRH was not associated with a measurable change in input conductance. It was especially evident during current-clamp recordings, when the diminutive TRH-induced current was still capable of causing a substantial depolarization. The ionic basis of the residual TRH-induced inward current remains to be determined. 6. We investigated the functional consequences of these mechanisms of action of TRH on spike firing behavior of HMs.(ABSTRACT TRUNCATED AT 400 WORDS)


GABAergic circuits sharpen tuning curves and modify response properties in the mustache bat inferior colliculus.

1. The influence of bicuculline on the tuning curves of 65 neurons in the inferior colliculus of the mustache bat was investigated. Single units were recorded with multibarrel electrodes where one barrel contained bicuculline, an antagonist specific for gamma-amino-butyric acid (GABA)A receptors. Fifty-nine tuning curves were recorded from units that were sharply tuned to 60 kHz, the dominant frequency of the bat's orientation call, but six tuning curves were also recorded from units tuned to lower frequencies and whose tuning curves were broader than the 60 kHz cells. Tuning curves were constructed from peristimulus time (PST) histograms obtained over a wide range of frequency-intensity combinations. Thus tuning curves, PST histograms evoked by frequencies within the tuning curve, and rate-level functions at the best frequency were obtained before iontophoresis of bicuculline and compared with the tuning curves and response properties obtained during the administration of bicuculline. 2. Three general types of tuning curves were obtained: 1) open tuning curves that broadened on both the high- and low-frequency sides with increasing sound level; 2) level-tolerant tuning curves in which the width of the tuning curve remained uniformly narrow with increasing sound level; and 3) upper-threshold tuning curves, which did not discharge to high-intensity tone bursts at the best frequency, thereby creating closed or folded tuning curves. 3. One major finding is that GABAergic inhibition plays an important role in sharpening frequency tuning properties of many neurons in the mustache bat inferior colliculus. In response to blocking GABAergic inputs with bicuculline, the tuning curves broadened in 42% of the neurons that were sharply tuned to 60 kHz. The degree of change in most units varied with sound level: tuning curves were least affected, or not affected at all, within 10 dB of threshold and showed progressively greater changes at higher sound levels. These effects were seen in units that had open, level-tolerant, and upper-threshold tuning curves. 4. A second key result is that bicuculline affected rate-level functions and/or temporal discharge patterns in many units. Bicuculline transformed the rate-level functions of 13 cells that originally had nonmonotonic rate level functions, from strongly nonmonotonic into weakly nonmonotonic or monotonic functions. It also changed the temporal discharge patterns in 22 cells, and the changes were often frequency specific.(ABSTRACT TRUNCATED AT 400 WORDS)


Experimental tests of a superposition hypothesis to explain the relationship between the vestibuloocular reflex and smooth pursuit during horizontal combined eye-head tracking in humans.

1. We used a modeling approach to test the hypothesis that, in humans, the smooth pursuit (SP) system provides the primary signal for cancelling the vestibuloocular reflex (VOR) during combined eye-head tracking (CEHT) of a target moving smoothly in the horizontal plane. Separate models for SP and the VOR were developed. The optimal values of parameters of the two models were calculated using measured responses of four subjects to trials of SP and the visually enhanced VOR. After optimal parameter values were specified, each model generated waveforms that accurately reflected the subjects' responses to SP and vestibular stimuli. The models were then combined into a CEHT model wherein the final eye movement command signal was generated as the linear summation of the signals from the SP and VOR pathways. 2. The SP-VOR superposition hypothesis was tested using two types of CEHT stimuli, both of which involved passive rotation of subjects in a vestibular chair. The first stimulus consisted of a "chair brake" or sudden stop of the subject's head during CEHT; the visual target continued to move. The second stimulus consisted of a sudden change from the visually enhanced VOR to CEHT ("delayed target onset" paradigm); as the vestibular chair rotated past the angular position of the stationary visual stimulus, the latter started to move in synchrony with the chair. Data collected during experiments that employed these stimuli were compared quantitatively with predictions made by the CEHT model. 3. During CEHT, when the chair was suddenly and unexpectedly stopped, the eye promptly began to move in the orbit to track the moving target. Initially, gaze velocity did not completely match target velocity, however; this finally occurred approximately 100 ms after the brake onset. The model did predict the prompt onset of eye-in-orbit motion after the brake, but it did not predict that gaze velocity would initially be only approximately 70% of target velocity. One possible explanation for this discrepancy is that VOR gain can be dynamically modulated and, during sustained CEHT, it may assume a lower value. Consequently, during CEHT, a smaller-amplitude SP signal would be needed to cancel the lower-gain VOR. This reduction of the SP signal could account for the attenuated tracking response observed immediately after the brake. We found evidence for the dynamic modulation of VOR gain by noting differences in responses to the onset and offset of head rotation in trials of the visually enhanced VOR.(ABSTRACT TRUNCATED AT 400 WORDS)


Depression of postsynaptic potentials by high-frequency stimulation in embryonic motoneurons grown in spinal cord slice cultures.

1. In embryonic cocultures of spinal cord, dorsal root ganglia, and muscle, excitatory postsynaptic potentials (EPSPs) were recorded in motoneurons during focal electrical stimulation of the dorsal root ganglia or the spinal cord. 2. EPSPs were depressed in amplitude at high-frequency stimulation relative to a control frequency of 0.5 Hz by 47 and 75% at 5 and 10 Hz, respectively. This was true for composite EPSPs and unitary EPSPs. 3. The depression showed a wide range of variability between individual experiments. The degree of depression at 5 Hz was negatively correlated to the rate of spontaneous excitatory input the motoneurons received. There was no correlation to the soma size, the average amplitude of the EPSPs, the rheobase, or the input resistance of the motoneurons. 4. An increase in latency of EPSPs was observed concomitant with or preceding the synaptic depression in most experiments. Total transmission failures, which were absent at low-frequency stimulation, appeared during depression. 5. Large incremental steps in amplitude could be seen during depression, suggesting that several release sites were switched off and on together. 6. Decreasing the extracellular calcium concentration from 5 to 1 mM led to a decrease in the frequency sensitivity of the synaptic efficacy and to a decrease of the EPSP amplitude and latency. 7. Measurements of the antidromic conduction of action potentials evoked in the axons and recorded in the somata of dorsal root ganglion cells revealed an increase in latency and the appearance of conduction failures at stimulation frequencies of 1-10 Hz. The frequency modulation of conduction was decreased in 1 mM compared with 5 mM external calcium. 8. Together these findings suggest that conduction failures in the presynaptic axons contribute to the synaptic depression of EPSPs in embryonic motoneurons.


The recording of odorant-induced mucosal activity patterns with a voltage-sensitive dye.

1. Fluorescence changes in the dye (WW 781) were monitored at 100 contiguous sites in a 10 x 10-pixel array on the bullfrog and salamander olfactory mucosas every 10 ms in response to odorous stimuli. The odorants were d-limonene, butanol, and amyl acetate, each presented at two concentrations with a 3:1 ratio. 2. The fluorescence signals elicited by these odorous stimuli were nearly identical in shape and time course to the electro-olfactograms (EOGs) recorded from the same animal under identical conditions. Like the EOGs, the fluorescence signals exhibited adaptation and were abolished by both Triton X-100 and ether. There was no measurable fluorescence when the tissue was not stained with the dye, and there was no change in fluorescence when, for stained tissue, nonodorized, humidified air was presented as the stimulus. 3. This technique presumably monitors the same events as the EOG, but has the advantage of simultaneously recording the odorant-induced activity from multiple sites across most of the mucosa. Thus this technique preserves subtle differences heretofore lost by other techniques both in the coarseness of their matrices and in the variability generated by trying to piece together, into one collage, results from numerous presentations given at different times. 4. In all preparations, there was a larger difference in the inherent activity patterns (derived from response magnitudes) between different odorants than between different concentrations of the same odorant. These differences were largest on the mucosa lining the floor of salamander's olfactory sac. d-limonene and butanol gave their largest responses near the internal and external nares, respectively, whereas the responses for amyl acetate were more uniform across the mucosal sheet. In contrast to the salamander, smaller differences were observed for both the roof and the floor of the bullfrog's olfactory sac. For the floor, both amyl acetate and d-limonene elicited similar patterns of response magnitude, whereas butanol differed from each of these odorants by eliciting a larger response on the anteriolateral aspect of the mucosa and a lesser response on the remainder. For the roof, different odorants produced different activity patterns, which had profiles not simply described as regions of maximal and minimal responsiveness. 5. Different inherent activity patterns based on temporal characteristics of the fluorescence responses were also observed for different odorants. Each odorant produced a different pixel-by-pixel pattern for the times at which the responses started and ended. For any given odorant, these temporal patterns paralleled the patterns given by response magnitudes.(ABSTRACT TRUNCATED AT 400 WORDS)


Responses of sagittally aligned Purkinje cells during perturbed locomotion: relation of climbing fiber activation to simple spike modulation.

1. The purpose of these experiments is to test the hypothesis that the synchronous activation of sagittally aligned Purkinje cells by a physiologically relevant stimulus is associated with an increase in the simple spike responses of the same neurons. 2. This hypothesis was tested using a perturbed locomotion paradigm in decerebrate locomoting ferrets. The responses of 3-5 sagittally aligned Purkinje cells were recorded simultaneously in response to the intermittent perturbation of the forelimb during swing phase. A data analysis is introduced, the real time postsynaptic response (RTPR), that permits the quantification of the simple spike responses of Purkinje cells in a manner that can be related to their complex spike responses on a trial-by-trial basis. 3. The data support the above hypothesis by illustrating that the amplitude of the combined simple spike responses across the population of Purkinje cells is correlated with the extent to which their climbing fiber inputs are synchronously activated. These findings together with an analysis of the gain-change ratio support the view that the synchronous climbing fiber input may be responsible for mediating this increased responsiveness. 4. More generally, the data suggest that the task- and/or behaviorally dependent activation of sagittal strips of climbing fiber inputs may provide a mechanism whereby the responsiveness of discrete populations of Purkinje cells can be selectively regulated, specifying the groups of neurons that will be most dramatically modulated by mossy fiber inputs activated by the same conditions.


Excitotoxic acid lesions of the primate subthalamic nucleus result in transient dyskinesias of the contralateral limbs.

1. To examine the role of the subthalamic nucleus (STN) in the pathogenesis of dyskinesias, the STN was experimentally lesioned with fiber-sparing excitotoxins in two awake monkeys. 2. A combined recording-injection device was used to locate and lesion the STN accurately under physiological guidance. A small amount (1 microliters) of ibotenic acid (10 micrograms/microliters) or kainic acid (1 micrograms/microliters) was injected into each of four to seven target sites in the STN. Postmortem histology confirmed that lesions were confined to the STN, and the volume of each lesion at each site was 4-11% of the total volume of the nucleus. 3. Approximately 20 min after the end of each injection, the frequency of movements increased in the distal portions of the upper and lower limbs contralateral to the injection site. Severe dyskinesias, involving the proximal joints to a greater degree than the distal, developed in the contralateral limbs after 60-80 min and lasted < or = 4 h. The pattern of involvement and time course were similar after each lesion. In the days after the lesioning, only rare dyskinesias were observed in the contralateral hands and feet, typically occurring when the animals were stimulated. 4. Despite the severe dyskinesias, there was no obvious effect on voluntary movements such as grooming or reaching. 5. These results suggest that reduction of STN activity plays a role in the production of dyskinesias.


Excitotoxic acid lesions of the primate subthalamic nucleus result in reduced pallidal neuronal activity during active holding.

1. To gain a better understanding of the pathophysiology of hemiballismus in primates, and to test directly the hypothesis that the subthalamopallidal projection is excitatory, we studied the effects of lesions of the subthalamic nucleus (STN) on neuronal activity in the globus pallidus (GP) of monkeys during performance of a motor behavioral task. 2. Animals were trained to position and hold a manipulandum to which torque pulses were applied, producing elbow flexion and extension. The activity of neurons in the external (GPe) and internal (GPi) segments of GP was recorded in two monkeys during task performance before and after STN lesions. The STN was lesioned by the fiber-sparing neurotoxins ibotenic acid and/or kainic acid. 3. After lesioning, the firing rate of neurons in both segments of GP, which was measured during the period of holding before torque application, was significantly decreased in both animals. The mean of discharge rates of GPi neurons decreased (P < 0.001) from 69.8 (n = 169, SD = 21.6) to 47.4 spikes/s (n = 180, SD = 22.6) after lesioning. The mean of discharge rates of GPe neurons decreased from 63.6 spikes/s (n = 218, SD = 25.1) before lesions to 41.0 spikes/s (n = 208, SD = 18.1) after lesioning. 4. These results provide further evidence that STN gives rise to a major excitatory input to both segments of the GP and support the hypothesis that dyskinesias result from decreased GPi output.


Primary motor cortical activity related to the weight and texture of grasped objects in the monkey.

1. Two monkeys were trained to grasp an object between the thumb and index finger and lift it to a vertical distance of 12-25 mm. Up to 12 different conditions defined by different combinations of object weights (15, 65, and 115 g) and four surface textures (oiled metal, smooth metal, fine and coarse sandpaper) were used. The apparatus was equipped to measure grip (prehensile) force, vertical (load) force, and object displacement. 2. The monkeys appropriately scaled the grip force for the weight and the coefficient of friction of the object. However, during the dynamic phase of the task (grasping and lifting), the monkeys increased the prehensile force in multiple steps, suggesting that they relied on sensory feedback from the fingers to attain an adequate grip force to lift the object rather than programming the lift in advance. 3. Single-unit activity of 248 neurons was recorded in the hand area of the primary motor cortex while the monkeys performed the task. Of 208 neurons tested for cutaneous and proprioceptive receptive fields (RFs), 96 were sensitive to cutaneous stimulation of the glabrous skin of the hand, whereas 82 received proprioceptive input from wrist and finger muscles. The concentration of neurons with cutaneous input was significantly greater in the rostral bank of the central sulcus compared with cells with proprioceptive RFs, which were more concentrated in the convexity of the precentral gyrus. 4. From the global sample, 199 cells were tested with the three object weights, and 128 of these with at least two surface textures were used in combination with the object weights. The discharge of 58/199 (29%) cells was modulated with the object weight. Cells with cutaneous (20/84, 24%) and proprioceptive (23/71, 32%) RFs were about equally responsive to the object weight. 5. A greater number of motor cortical neurons were influenced by surface texture than by object weight. Of 128 cells tested with at least two surface textures, 67 (52%) showed a modulation of their activity as a function of texture. A significantly greater proportion of neurons with cutaneous RFs (40/63, 63%) showed differential activity as a function of object texture than cells receiving proprioceptive input (21/47, 45%). 6. Weight- and texture-related neurons were not distributed equally in the rostrocaudal dimension of the motor cortex. Only 8% of texture-related cells were located in the convexity of the precentral gyrus, whereas 30% of weight-related neurons were recorded from this rostral zone.(ABSTRACT TRUNCATED AT 400 WORDS)


Primary motor cortical responses to perturbations of prehension in the monkey.

1. Two monkeys were trained to grasp, lift, and hold an object within a vertical position window. A downward force-pulse perturbation was delivered during stationary object holding to simulate slip of the object due to gravity. The responses evoked by the perturbation were studied in 189 neurons of the hand area of the primary motor cortex. In addition, the slip-evoked responses were compared with the modulation of neural discharge with textures and weights described in the previous paper. 2. The perturbation evoked responses with sharp onsets in the majority of motor cortical neurons (115/189, 61%) active during the task. The majority of the responses were of sufficiently short latency (43.17 +/- 17.24 ms, mean +/- SD) to have participated in the reflex grip force increase that followed at latencies from 50 to 100 ms. 3. Although a similar proportion of neurons with cutaneous (43/70) or proprioceptive (35/59) receptive fields (RFs) were responsive to the perturbation, the cutaneous afferents provided a stronger excitation of motor cortical cells than the feedback originating from proprioceptive receptors. 4. The covariation of the neural discharge related to the surface texture of the grasped object and the responsiveness to object slip was studied in 89 cells tested with the perturbation and with more than one surface texture on unperturbed trials. Within this population, motor cortical cells with cutaneous RFs were more sensitive to the perturbation (25/31) than neurons receiving proprioceptive input (8/16). Furthermore, all (17/17) neurons with cutaneous RFs that were more active with the smooth than with the rough surface textures showed a vigorous response to the perturbation. 5. A detectable downward displacement of the object was not always necessary to excite neurons with cutaneous RFs and whose activity increased with the smooth textures. Their sensitivity to the perturbation was consistent with the hypothesis that the cutaneous afferent activity generated by object slips or shear forces on the skin contributed to the increased discharge when lifting objects of slippery surface textures. The activity of these slip- or shear-sensitive cells may have contributed to the reflex grip force increases and to the greater sustained muscular activity needed to lift smooth objects. 6. Ten cells that were excited by stroking of the glabrous skin of the hand decreased their discharge frequency during the task even though their RFs were in direct contact with the object. Most of these neurons (7/10) did not respond to the object slip, and three cells had very weak responses to the perturbation.(ABSTRACT TRUNCATED AT 400 WORDS)


Role of irregular otolith afferents in the steady-state nystagmus during off-vertical axis rotation.

1. During constant velocity off-vertical axis rotations (OVAR) in the dark a compensatory ocular nystagmus is present throughout rotation despite the lack of a maintained signal from the semicircular canals. Lesion experiments and canal plugging have attributed the steady-state ocular nystagmus during OVAR to inputs from the otolith organs and have demonstrated that it depends on an intact velocity storage mechanism. 2. To test whether irregularly discharging otolith afferents play a crucial role in the generation of the steady-state eye nystagmus during OVAR, we have used anodal (inhibitory) currents bilaterally to selectively and reversibly block irregular vestibular afferent discharge. During delivery of DC anodal currents (100 microA) bilaterally to both ears, the slow phase eye velocity of the steady-state nystagmus during OVAR was reduced or completely abolished. The disruption of the steady-state nystagmus was transient and lasted only during the period of galvanic stimulation. 3. To distinguish a possible effect of ablation of the background discharge rates of irregular vestibular afferents on the velocity storage mechanism from specific contributions of the dynamic responses from irregular otolith afferents to the circuit responsible for the generation of the steady-state nystagmus, bilateral DC anodal galvanic stimulation was applied during optokinetic nystagmus (OKN) and optokinetic afternystagmus (OKAN). No change in OKN and OKAN was observed.(ABSTRACT TRUNCATED AT 250 WORDS)


Vestibular inputs to brain stem neurons that participate in motor learning in the primate vestibuloocular reflex.

1. Previous studies have described a subpopulation of interneurons in the vestibuloocular reflex (VOR) pathways that express large changes in their responses to head turns in conjunction with motor learning in the VOR. These neurons are called flocculus target neurons (FTNs) because they are inhibited at monosynaptic latencies by stimulation of the flocculus and ventral paraflocculus. 2. Electrical stimulation of the vestibular labyrinth revealed that FTNs receive excitatory monosynaptic inputs from the ipsilateral vestibular labyrinth and longer-latency, excitatory inputs from the contralateral labyrinth. 3. Our data show that commissural inhibition, which has been thought to be an important feature of vestibular processing, does not provide the dominant inputs from the contralateral labyrinth to FTNs. Instead, the inputs from both labyrinths are excitatory and may be functionally antagonistic. Changes in the balance of excitatory inputs from the two horizontal canals to FTNs could contribute to motor learning in the VOR.


Saccade initiation and latency deficits after combined lesions of the frontal and posterior eye fields in monkeys.

1. Monkeys were trained to perform horizontal visually guided saccades. Latency was measured before and after bilateral lesions of the frontal eye field (FEF) and after combined lesions of both the FEF and the posterior eye field. Destruction of either of these regions alone causes only modest deficits of eye movement, but destruction of both together produces profound oculomotor impairment. The results support the proposal that purposeful eye movements are controlled by a distributed corticocortical network that includes nodes in frontal and parieto-occipital regions.


Endogenous nitric oxide required for an integrative respiratory function in the cat brain.

1. The involvement of nitric oxide (NO) in the respiratory function of the pons was examined by microinjecting NO synthase-related drugs into discrete regions of the pontine respiratory group (PRG) in decerebrate and decerebellate cats. 2. Microinjection of N omega-nitro-L-arginine (L-NNA, inhibitor of NO synthase), but not D-NNA (the inactive enantiomer), significantly prolonged the duration of inspiration in all 10 cats when lung inflation was withheld. 3. The prolongation of inspiration produced by L-NNA was partially reversed in three cats by microinjections of L-arginine (NO synthase substrate) at the same sites. 4. We conclude that endogenous production of NO from L-arginine in the PRG region is involved in the normal function of the pontine pneumotaxic mechanism. These findings provide the first conclusive evidence that endogenous NO formation is involved in the mechanisms associated with respiratory rhythm generation.


Intermittent mandatory ventilation with continuous negative pressure compared with positive end-expiratory pressure for neonatal hypoxemia.

The use of continuous negative pressure was prospectively studied in 30 preterm and term hypoxemic (PaO2 < 45 mm Hg) neonates. Infants were randomly assigned to either positive end-expiratory pressure or continuous negative pressure if conventional positive pressure ventilation failed to improve oxygenation. Crossover to the alternative therapy occurred if infants remained hypoxemic after 2 hours. In the continuous negative pressure group, 2 (13%) crossed over to positive end-expiratory pressure, whereas 11 (73%) in the positive end-expiratory pressure group crossed over to continuous negative pressure (p = 0.003). Only five patients remained in the positive end-expiratory pressure group 36 hours after randomization. Compared with positive end-expiratory pressure, continuous negative pressure significantly increased PaO2 (69 +/- 17 mm Hg vs 36 +/- 8 mm Hg) and arterial-alveolar ratio (0.098 +/- 0.070 vs 0.057 +/- 0.014) 30 minutes after randomization and after crossover to continuous negative pressure (60 +/- 12 mm Hg vs 37 +/- 5 mm Hg, and 0.154 +/- 0.096 vs 0.058 +/- 0.009). The use of continuous negative pressure did not increase morbidity. Overall survival was 83.3%. Only three infants were referred to extracorporeal membrane oxygenation. Rescue therapy with continuous negative pressure is effective in infants with refractory hypoxemia and may be considered before referral for extracorporeal membrane oxygenation.


Dysphoric distress in childbearing women.

Previous research on depression in childbearing women has focused on the presence or absence of clinical depression. Little attention has been paid to the distress caused by the presence of depressive symptoms in the absence of the full syndrome of clinical depression. A convenience sample of 202 healthy, married, primigravid women who were free of psychiatric symptoms were assessed at 10 to 14 weeks and 30 to 32 weeks of pregnancy and at 1 to 2 weeks and 14 weeks post partum. Depression symptoms were measured by using the Schedule of Affective Disorders and Schizophrenia, the standardized clinical interview for research and depression of The National Institute of Mental Health. Data from the Schedule of Affective Disorders and Schizophrenia indicated that only 5% of the women met criteria for clinical depression but approximately 50% of the sample reported clinical levels of three or more depressive symptoms. Anger, fatigue, psychic anxiety, and worry were the most frequently endorsed symptoms at each assessment point. The implications of these findings for symptom management and health promotion for childbearing women are discussed.


Do postsuctioning transcutaneous PO2 values change when a neonate's movements are restrained?

The purpose of this research was to examine the effects of containment (restraint of an infant's movements) on premature infants' postsuctioning transcutaneous PO2 values. The hypothesis was that premature infants receiving containment would have significantly different postsuctioning transcutaneous PO2 levels than infants receiving no containment. Premature infants with respiratory disease require suctioning to remove excess secretions from their lungs. Research studies document a variety of infant responses to suctioning; hypoxia, hypoxemia, increased blood pressure, bradycardia, increased intracranial pressure, and increased cerebral blood flow velocity. Most studies have examined only a few isolated variables and the magnitude and duration of hypoxemia in response to suctioning. Our sample comprised 24 infants less than 72 hours of age, who had respiratory distress syndrome and had been born at between 24 and 33 weeks' gestational age. The setting was a neonatal intensive care unit of a large county hospital. The same nurse performed the suctioning and containment procedures in all subjects. Student's t-tests and analysis of variance were carried out to determine the effect of the technique.


Nonimmune hydrops fetalis: case reports and brief review.

We report two cases of nonimmune hydrops fetalis diagnosed prenatally. One fetus died in utero, and the second fetus survived and the infant was discharged from the intensive care nursery at 4 weeks of age. A brief review of the literature and the difficulties in arriving at a diagnosis and the management are described, along with certain prognostic factors determining the outcome.


Evolution of a neonatal gentamicin dosing protocol in a small community hospital.

The effects of conventional dosage of gentamicin of 2.5 mg/kg given every 12 hours was retrospectively investigated in a small community hospital. Consistent with previous results in large hospitals, the conventional dosage of gentamicin commonly resulted in serum concentrations associated with toxicosis. Results were compared with those obtained prospectively according to a gentamicin dosing protocol that used a formula based on gestational age. The gestational age regimen provided similar peak and significantly lower trough serum concentrations; statistical analysis indicated no demographic differences in the compared groups. Very few neonates who received gentamicin according the gestational age formula were exposed to gentamicin serum concentrations associated with an increased risk of toxicosis. An absence of any significant differences in mean peak and trough serum concentrations in subgroups of neonates treated according to the gestational age formula suggested that use of the gentamicin dosing protocol was appropriate for all neonates. The dose of 3.5 mg/kg used in the gestational age formula was predicted to have resulted in initial gentamicin peak serum concentrations > 5 micrograms/ml in nearly 90% of neonates. The experience obtained with the gestational age formula allowed revision of the gentamicin dosing protocol to provide for more cost-responsible serum concentration monitoring.


Effect of exercise on uterine activity in the patient in preterm labor.

Preterm labor patients are at risk for physiologic complications associated with long-term bed rest. Although conditioning exercise programs are recommended for patients confined to bed rest, no studies have been reported that have evaluated the effects of exercise on uterine activity in women with preterm labor. A pilot study with 10 women was conducted to evaluate the short-term effects of exercise with a protocol involving pretesting and posttesting of uterine activity. The results indicated minimal changes in the frequency of uterine contractions after exercise. Future research is recommended with larger and more diverse samples to evaluate both short- and long-term effects of exercise throughout high-risk pregnancies.


Significantly improved peripheral intravenous catheter performance in neonates: insertion ease, dwell time, complication rate, and costs.

A prospective, randomized, controlled study was performed in neonates in an intensive care nursery to compare the performance of a peripheral intravenous catheter made of Aquavene material (test catheter) with that of a conventional peripheral catheter made of Teflon material (control catheter). Aquavene is a newly developed biomaterial that softens and expands on contact with body fluids. A total of 105 catheters (50 test and 55 control) were inserted in 63 neonates. The median time to a catheter-related complication was 3.60 days for the test catheters and 1.75 days for the control catheters (p = 0.0007). Infiltration rate for the test catheters was 56% as compared with 78% for the control catheters (p = 0.03). The test catheters provided fewer catheter-related complications (p = 0.006), with 34% of the test catheters reaching end of therapy as compared with 9% of the control catheters (p = 0.004). On average, 1.8 test catheters were used per insertion versus 2.3 control catheters (p = 0.08). The test catheters were rated easier to insert (p = 0.05), with a shorter time required for insertion. Because of improved performance, cost savings were realized with the test catheters after the first day of therapy, even though the per unit cost of the test catheter was greater. These data indicate that the test catheter, made of Aquavene material, is superior to the Teflon catheter for peripheral intravenous therapy in neonates.


Acute hemorrhagic gastritis in the newborn infant.

We report three cases of hemorrhagic gastritis in term infants that led to massive bleeding of life--threatening proportions in the first 24 hours of life. In all three cases, bleeding was controlled by conservative therapeutic management. Management of this unusual entity in the newborn infant is discussed.


Modeling the power of the aging human eye.

A hypothesis is presented that may explain why the aging eye does not become myopic with age. The power of the eye lens is predicted with a modeling approach to determine how the form of the refractive-index gradient within the lens can change to maintain a constant power in spite of age-related curvature increase. Methods used include published age-dependent data on the optical parameters of the eye, a mathematical model of the lens based on elliptical isoindicial contours, and a refractive-index profile that can be expressed as a power series in the distance from the lens center. The kinds of change in profile required to prevent the eye from becoming myopic as its lens grows are shown.


Survival, excision repair and inhibition of DNA synthesis in normal human skin fibroblasts exposed to simulated sunlight.

The responses of normal human skin fibroblasts exposed to simulated sunlight produced by a solar simulator were examined. The parameters investigated were cellular survival, excision repair and the inhibition and recovery of DNA synthesis. The latter two effects were examined using the bromodeoxyuridine photolysis assay and the alkaline step elution assay respectively. The results of these experiments are consistent with the conclusion that the lesions induced by simulated sunlight represent a mixture of damage which elicits cellular responses and repair mechanisms similar to those manifested by cells irradiated with UVC and UVA radiation.


The extra-weak chemiluminescence generated during oxidation of some tetracycline antibiotics. II. Peroxidation.

This study was undertaken to establish the mechanism of chemiluminescence during the oxidation reaction of tetracycline antibiotics in the presence of molecular oxygen and H2O2. The spectral distribution of chemiluminescence and fluorescence and the quantum yields of chemiluminescence were measured. The chemiluminescence spectrum measured with cut-off filters revealed one broad blue-green band and bands with maxima at 580, 640 and 700 nm. The bands at 580, 640 and 700 nm were similar to those observed for singlet molecular oxygen. The effect of superoxide radical, hydroxyl radical inhibitors, singlet oxygen quenchers and D2O as solvent on the light emission was also studied. The formation of singlet oxygen during the oxidation of the investigated tetracyclines was also checked using the spectrophotometric method based on the bleaching of p-nitrosodimethylaniline. A mechanism for the reactions generating electronically excited compounds is proposed.


Steady state and time-resolved spectroscopic studies on zinc(II) phthalocyanine in liposomes.

Zinc(II) phthalocyanine (ZnPc), a potential second-generation phototherapeutic agent for tumours, has been incorporated into small unilamellar vesicles (SUVs) (diameter, 52 nm) and large unilamellar vesicles (LUVs) (diameter, 84 nm) of dipalmitoyl-phosphatidylcholine (DPPC). Absorption spectroscopy, as well as steady state and time-resolved fluorescence emission studies, indicate that ZnPc is monomeric in SUVs at a stoichiometric concentration below 0.25 microM (corresponding to an actual endoliposomal concentration of about 0.5 mM), while in LUVs it is monomeric below 2 microM. The fluorescence lifetime of the monomer is 3-3.5 ns. Upon increasing the ZnPc concentration, aggregated derivatives are formed, which are characterized by shorter fluorescence lifetimes (1.2-1.5 ns; 0.4-0.6 ns). The possible implications of these observations for the phototherapeutic efficiency of ZnPc are briefly discussed.


Haematoporphyrin derivatives: distribution in a living organism.

Pharmacokinetics of accumulation in organs and tissues was studied for two haematoporphyrin-based photosensitizers. These sensitizers, haematoporphyrin derivative (HpD) and an oligomeric haematoporphyrin (OHp), contained different amounts of monomeric fraction (25% and 5% respectively) and in OHp the macrocycles were bonded together with ether bonds. OHp was shown to accumulate in tumours in higher amounts than HpD. The maximal tumour to tissue concentration ratio for OHp was 6.7 observed 54 h after injection; the same ratio for HpD was 2.8 after 48 h.


Cytokine production after helium-neon laser irradiation in cultures of human peripheral blood mononuclear cells.

The effects of laser light on the immune system have not been extensively characterized. Low-power laser sources, such as the helium-neon (He-Ne) laser with a wavelength of 632.8 nm, have been found to produce photobiological effects with evidence of interference with immunological functions. We have investigated the effects of He-Ne laser irradiation on Ficoll-Hypaque-isolated human peripheral blood mononuclear cells (PBMC). Cultured cells were irradiated for various times at two selected intensities and then stimulated with different mitogens. The rate of incorporation of 3H-thymidine into the DNA of stimulated cells decreased with increasing energy density. The levels of interleukin-1 alpha (IL-1 alpha), interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) in supernatants of the cultures were determined (irradiated either before or after stimulation). When stimulating cells after irradiation, significantly increased levels of all cytokines were detected after 30 min of irradiation (18.9 J cm-2), whereas after 60 min of irradiation (37.8 J cm-2) cytokine levels were found to be significantly decreased.


Monoline argon laser (514 nm) treatment of benign pigmented lesions with long pulse lengths.

A dichroic filter was adjusted in order to make use of the green line of an argon laser for the treatment of pigmented lesions (actinic and senile lentigo, ephelis, café-au-lait marks and spilus nevus). Using a power of 1.5 W, a spot size of 0.5 mm and pulse lengths of 200 or 300 ms, satisfactory elimination of 620 pigmented cutaneous lesions was achieved. Although the pulse lengths used were much longer than the thermal relaxation time of the melanosomes, the histology after treatment showed little damage of adjacent structures. Good restoration of the epidermis and a return of normal pigmentation led to excellent cosmetic results, with few complications.


A novel method for measuring intracellular pH: effect of neutron irradiation on pHi of transformed cells.

A new flow cytometric method was developed for measuring the intracellular pH (pHi) of mammalian cells using a fluorescent pH indicator dye 2',7-bis-(2-carboxyethyl)-5(and-6)-carboxyfluorescein (BCECF). Emission intensities (or their ratios) measured from BCECF-loaded cells can be converted into absolute pHi values using appropriate calibration curves. By comparison of several possible measuring and data evaluation procedures a double-ratio method was suggested as the most advantageous protocol to yield reliable intracellular pH data. This method allows pHi to be determined on a cell-by-cell basis corrected for cell volume and change in geometry of input-output optics of the flow cytometer. Our method applies a standard calibration curve and does not necessitate its reconstruction for each new set of measurements. Cells of the OKT-4 and OKT-8 hybridoma lines were exposed to neutron irradiation of different doses. Irradiated cells underwent a biphasic alkalinization; an instantaneous effect detected within 1.5 h was found to be intensified over 24 h. For the interpretation of data we suggest that the increase in cytoplasmic pH following neutron treatment is evoked by two mechanisms.


Cytogenetic effects of singlet oxygen.

Singlet oxygen was generated in the gas phase at atmospheric pressure by the method of heterogeneous photosensitization. In vitro exposure of human lung WI-38 fibroblasts to gas-phase singlet oxygen resulted in sister chromatid exchange.


Conformity, peer pressure, and adolescent receptivity to treatment for substance abuse: a research note.

To explore the possibility that peer influences not only contribute to adolescent substance abuse but shape feelings about being in treatment for substance abuse, forty adolescent inpatients were surveyed. Misconduct, including substance abuse, was predicted best by perceived peer pressure toward misconduct, low opinions of the value of treatment by disposition to conform to antisocial peers, and sense of stigma associated with being treated by perceived peer pressure toward conformity. Concerns over peer acceptance may be one basis for resistance to substance abuse treatment.


Personal and social drinking motives, family drinking history, and problems associated with drinking in two university samples.

Two drinking motives scales, Negative Personal (NP) motives and Positive Social (PS) motives, derived from Mulford and Miller's Definitions of Alcohol Scales, and a Negative Family Models (NFM) scales designed to reflect family modeling of drinking-related problems were evaluated for internal consistency and association with college students' scores on a drinking-related Social Complications (SOCCOMP) scale. In both initial (n = 553) and cross-validation (n = 293) samples, all four scales demonstrated high internal consistency. Multiple regressions of NP, PS, and NFM scales, together with measures of quantity and frequency of drinking on SOCCOMP for both samples, yielded highly significant multiple R's, confirming the additive association of these measures with problem drinking outcomes. An unanticipated finding of positive associations between PS drinking motive and SOCCOMP is reported.


Campus attitudes toward alcohol and drugs in a deep southern university.

In our zeal to deal with alcohol and drug abuse, we may have a distorted picture of what the majority of college students actually think about alcohol and drug use. Students in this study done at a public university located in the Deep South report being generally intolerant of substance abuse.


Environmental and personality differences between children of alcoholics and their peers.

Nonclinical, adolescent children of alcoholics (COAs) and their peers from nonalcoholic homes (CONAs) responded to questionnaires of environmental variables, depression, and anxiety. Multivariate (discriminant) analyses revealed several meaningful differences between the two groups. Although the two groups differed on the measures of anxiety and depression, environmental stressors contributed most to the discriminant function that differentiated between the two groups. Also, gender differences were discovered, suggesting that males and females perceive problem drinking differently and that home environments may be different for the two genders. Implications for research and intervention are discussed.


Drug abuse and eating disorders: prevention implications.

This article explores the relationship between drug and alcohol abuse and eating disorders in a sample of adolescent females using a self-report methodology. An Eating Disorders Risk (EDR) Scale is adopted and correlated with drug and alcohol use, other forms of deviance, family and peer relationships, and depression. The findings support the concept of a generalized theory of addictions based on psychosocial, family, and peer factors. Family and peer prevention applications and a need for further research on the correlates of depression are discussed.


An investigation of cognitive style and alcohol/work-related problems among Naval personnel.

This study examines the relationship between cognitive style (i.e., information, normative, and diffuse orientation, and commitment) and alcohol/work-related problems. A random sample of Naval personnel (n = 2000) with less than two years of service toward their first enlistment was sent a questionnaire to assess cognitive style [1] and alcohol/work-related problems. A total of 899 respondents (45.0%) returned their questionnaires. Findings support prevention strategies that incorporate problem-solving, decision-making, and coping strategies, particularly among participants who employ diffuse problem-solving/coping strategies (lack of exploration and commitment, avoidance of problems). Correlations between cognitive style and alcohol/work-related problems are theoretically compatible. Diffuse orientation scores are positively related to both alcohol- and work-related problems, while norm and information orientation scores are negatively related to both measures. Collectively, cognitive style measures explain 11.4 percent of the variability in alcohol-related problems, and 14.0 percent of the variability in work-related problems.


Perception of alcoholism among Jewish, Moslem and Christian teachers in Israel.

This article describes a survey which investigated perception of alcoholism among Jewish, Moslem and Christian teachers in the north of Israel during the spring of 1991. Data were obtained from a sample of 553 teachers. The teachers were asked to agree or disagree with items associated with the disease concept or with the moral concept of alcoholism. The findings indicate differences in the perception of alcoholism among teachers of different religions, education levels, gender, and drinking practices. No differences were found among teachers of different ages or among those working in different types of schools.


Tools for drug and alcohol education: using decision worksheets in personal problem solving.

Previous research has indicated that poor decisions with regard to drugs (including alcohol) and other issues involving personal risks often stem from poor decision-making strategies. This study examines the use of decision worksheets in training individuals to employ better decision-making strategies. Forty-two students enrolled at Texas Christian University participated in a two-session, four-hour study. An experimental group and a control group were asked to read decision-making scenarios related to alcohol usage. Participants were then requested to rate a given list of possible alternatives, and to write a persuasive essay defending their ratings. The experimental group was given the same written scenario with a decision worksheet related to the scenario as a supplement. The essays were scored on several dimensions by two raters. Multivariate analyses indicated that the experimental group had higher mean scores than the control group on measures of "overall goodness," intensity, and inclusion of elements of feasibility, costs, and benefits. In addition to decision worksheets appearing to be a promising approach to training decision-making skills related to alcohol, persuasive essays appear to have promise in evaluating and extending the usage of decision worksheets.


Surgical complications in children after liver transplantation.

The frequency of surgical complications after liver transplantation remains high. Sixty transplants were done in 48 patients during 4 years. Eleven patients were retransplanted (re-transplant rate, 20%) for primary nonfunction (6), arterial thrombosis (3), warm ischemia (1), and rejection (2). Right pleural effusions were drained in 13 patients and left ones in 2. Forty-eight re-explorations excluding retransplantation were performed in 20 patients. Twelve laparotomies were for control of postoperative intraabdominal bleeding. The majority of these patients (8/10, 80%) were transplanted with reduced-size grafts. Early postoperative vascular complications were detected in 12 grafts (5 portal vein occlusions, 7 arterial thromboses). All 5 patients with portal vein (PV) occlusions were reexplored, and PV flow was reestablished in all 5. Biliary leaks were diagnosed in 6 patients and were associated with arterial thromboses in 2 cases. Reoperation was required in 4 of 6 patients. Bowel perforation occurred in 4 patients; 2 small bowel, 1 duodenum, and 1 colon. There was 1 postoperative bowel obstruction requiring laparotomy. Two splenectomies were required in 4 patients with splenic infarction. Resection of part of a transplanted liver was done in 1 patient to exclude septic infarcts. Pancreatitis was diagnosed in 4 patients and one required laparotomy for control of pancreatic hemorrhage. Intraabdominal abscesses required open drainage in 2 patients and percutaneous drainage in 4. Seven thoracotomies were done in 6 patients: 5 open lung biopsies, 1 for control of hemorrhage, and 1 for diaphragmatic plication. The current high survival rates following liver transplantation require aggressive surgical management of a myriad of complications and numerous procedures are necessary both as treatment modalities and as diagnostic aids.


Risk of malignancy in bilateral streak gonads: the role of the Y chromosome.

Although girls with Turner's syndrome (45,X) are not at risk for malignancy, patients with feminizing testicular syndrome with XY chromosome composition and patients with "mixed gonadal dysgenesis" are at risk for malignancy, and bilateral gonadectomy is performed. We have treated seven girls with "Turner-like" syndrome, who we believe are also "at risk" for development of malignancy and in whom gonadectomy should be performed. We present seven cases of phenotypically typical females, without sexual ambiguity, who presented with primary amenorrhea and short stature (5) and/or minor dysmorphic features (2). Chromosome analysis showed 45,X karyotype plus a fragment that we could not rule out as being part of a Y chromosome (in one patient a complete Y chromosome). In two patients, the fragment was subsequently positively identified as a Y, using a DNA probe. In view of the known high incidence of development of gonadoblastoma in the dysgenetic gonads of phenotypic females with a Y chromosome, bilateral gonadectomy was performed in these girls. Bilateral genital streaks with normal uterus and Fallopian tubes were found in all patients. In two patients unsuspected gonadoblastoma, without metastases, was found. In five cases, Leydig cells and tubular structures resembling rete testes were found, cells that are associated with Y-chromosomal tissue. We stress the need for complete chromosomal evaluation of phenotypically female patients with primary amenorrhea or features of Turner's syndrome. If a Y chromosome or the possibility of a Y chromosome cannot be excluded, gonadectomy should be performed because of the risk of malignancy.


Atypical tuberculosis in the pediatric patient: implications for the pediatric surgeon.

Atypical species of mycobacteria (AMB) are now the most common cause of granulomatous lymphadenopathy. It is important for pediatric surgeons to be aware of this disease, because excision is the mainstay of therapy. We have reviewed the experience with this disease in Alberta by reviewing the records of the Provincial Laboratory of Public Health from 1979 to 1990. This facility reviews all tuberculosis cultures for the province. A total of 74 cases of infection caused by AMB were identified in patients under the age of 15. Complete records were available for 53 of these cases. These infections were characterized by a short history (11.2 weeks) of remarkably nontender regional lymphadenopathy (usually cervicofacial, 45/50) in young (average age, 13.6 months), caucasian (48/53) children. Attempts to treat these lesions by incision and drainage or drug therapy were unsuccessful (12/12 failed), whereas primary excision was successful in 33 of 37 cases. Secondary excisions were also successful in 16 of 16 cases where required. The annual rate of AMB over the study period was 1.21 cases per 100,000 children; the rate of M tuberculosis lymphadenopathy was 0.3 per 100,000. In the absence of specific risk factors for human tuberculosis (family history, native Indian or Asian ethnic origin) AMB is the most likely cause of prolonged painless lymphadenopathy and should be treated early by complete excision.


Spinning the wheels: a CAPS survey of ethical issues in pediatric surgery.

To evaluate decision-making factors of pediatric surgeons when faced with ethical dilemmas in a clinical setting, questionnaires were mailed to members of the Canadian Association of Paediatric Surgeons. The surgeons were asked to respond to scenarios regarding ethical dilemmas in the treatment of children. Fifty-one responses (57%) were computer analyzed based on chosen responses to the clinical dilemma and demographic factors such as age, sex, marital status, country of citizenship, religion, and "religiousness," a determination of religious conviction as viewed by the respondent. In addition, ethical convictions were sought regarding abortion, fetal research, AIDS, HIV testing, denial of medical care due to religious beliefs (Jehovah's Witness), and limitations in health care access for indigents. In general, respondents found it difficult to separate ethical guidelines for determining aggressive treatment--absolute value of life; best interests of the child; parental authority; and ability of the child to engage in social, intellectual, or emotional attachments (quality of life)--in the face of actual patient care issues. In fact, results of this survey indicate that the operating surgeon applies his/her medical knowledge and surgical "experience" to each individual case, incorporating his or her own ethical beliefs (in a respondent's words: "In the operating room, the surgeon must satisfy his own conscience in making decisions") while cognizant of legal guidelines for "standard care" ("Decisions would be based on personal experience, and what the local society believes to be right").(ABSTRACT TRUNCATED AT 250 WORDS)


Facilitating the operative exposure of the portal plate in cases of biliary atresia by dislocating the whole liver onto the abdominal wall.

Obtaining adequate exposure of the portal plate in cases with biliary atresia can tax the ingenuity of the surgeon. The successful completion of a hepatic portoenterostomy depends on it. Mobilising the liver and dislocating it into an ex vivo-like position on the anterior abdominal wall simplifies this step of the operation. It achieves maximal visualisation and access to the anatomy of the liver port. When used correctly by the surgeon this technique is not complicated by hepatic or caval blood flow occlusion. Its use in over 40 clinical cases has not resulted in any major mishap.


Infections in severely traumatized children.

To study the incidence and types of infection among severely traumatized children, we reviewed the medical charts of 212 children, hospitalized following traumatic injury, who received antibiotics at sometime during their hospitalization. Infection occurred in 19%. Eleven children had trauma-related infections, whereas 29 (71% of those infected) had 36 nosocomial infections. Tracheitis, sepsis, and urinary tract infections were the most common nosocomial infections and were diagnosed in the second week (10 +/- 3 days) following injury. Nosocomial infections were more likely to develop in children who were more severely injured and who had a greater number of invasive procedures. Severe head injury (cerebral edema or subarachnoid hemorrhage) was more common in those with nosocomial infection (P < .0002, odds ratio 6.8, 95% confidence interval 2.2 to 21.3). Those without these injuries were much less likely to develop nosocomial infections (specificity 97% and negative predictive value 86%). Finally, the development of any nosocomial infection prolonged the hospitalization by a mean of 16 +/- 6 days when comparing children with the same degree of traumatic injury. Prevention of nosocomial infection in children with severe trauma will significantly reduce length of hospitalization.


Is the metabolic response to sepsis in skeletal muscle different in infants and adults? An experimental study in rats.

In this study we compared the effect of sepsis on muscle protein metabolism in infant (3 to 4 weeks) and adult (3 to 4 months) rats. Sepsis was induced by cecal ligation and puncture (CLP). Control animals underwent sham operation. Sixteen hours after CLP or sham operation, metabolic studies were performed in incubated intact extensor digitorum longus muscles from infant rats or in strips of the same muscle from adult rats. Protein synthesis rate was determined as incorporation of 3H-phenylalanine into protein; total and myofibrillar protein breakdown rates were determined as release of tyrosine and 3-methylhistidine, respectively. Mortality rate following CLP was similar in both age groups. Basal protein synthesis rate was 3 times higher, total protein breakdown rate was 50% higher, and myofibrillar protein breakdown rate was 3 times higher in infant than in adult animals. However, the relative changes in protein turnover rates induced by sepsis were similar in infant and adult rats: protein synthesis rate decreased by approximately 30%, total protein breakdown increased by 40% to 50%, and myofibrillar protein breakdown increased severalfold. The data suggest that despite prominent differences in basal protein turnover rates between infant and adult rats, the effect of sepsis on muscle protein metabolism is not age dependent.


Intralingual cysts of foregut origin.

Intralingual cysts lined by epithelium of foregut origin are rarely reported. We present 16 patients seen over an 8-year period (1983 to 1990) with such lesions. Respiratory and squamous epithelium were the most commonly encountered. These unusual cysts generally presented in the neonatal period with feeding difficulty. Two children had multiple cysts. Histological varieties of epithelia are described and the clinical features are discussed. From our experience we conclude that these cysts are adequately treated by complete surgical excision through a sagittal glossal split. This can be safely done electively in the neonatal period. Cyst aspiration was found to be inadequate definitive treatment.


Solitary thyroid nodules in 71 children and adolescents.

Seventy-one children and adolescents with a solitary nodule of the thyroid gland were seen over a 27-year period and all had their nodules removed surgically. All of the patients had preoperative thyroid scintiscans, 55 of which showed a cold nodule. The most common cause of solitary thyroid nodules was follicular adenoma. Fourteen of the 55 cold nodules were malignant (25.5%) while no malignancies were present in warm or hot nodules. Available diagnostic methods for attempting differentiation of benign from malignant solitary nodules are reviewed and recommendations to their clinical management as derived from our experience are presented.


Limited pulmonary resections for congenital cystic adenomatoid malformation of the lung.

Congenital cystic adenomatoid malformations (CAMs) are rare lung lesions characterized by the presence of a multicystic mass of pulmonary tissue. To clarify the surgical management of CAM of the lung, we reviewed our institutional experience with 34 patients with histologically documented CAM. Symptoms developed in the first 2 days of life in 20 patients; 14 patients developed symptoms a median of 69 days (range, 22 days to 15 years) after birth. A diagnosis of CAM was confirmed at thoracotomy in all patients. Four patients were treated with a limited pulmonary resection for disease confined to one lobe. Seven patients underwent a composite resection involving a lobectomy plus limited resection of the second lobe. One patient underwent pneumonectomy for a severely malformed lung. The remainder of the patients were treated with anatomic lobectomy. The only recurrence was a patient who had a partial cystectomy performed at the initial operation. We conclude that in the appropriate malformation subtype, limited pulmonary reactions can preserve lung tissue and may prevent subsequent complications of CAM.


Prenatal ultrasonography and early surgery for congenital cystic disease of the lung.

With the recent advent of prenatal ultrasound as a routine screening procedure, diagnosis of congenital cystic lung disease has been made in utero, raising the possibility of elective surgery for these lesions early in infancy before the patient develops respiratory distress or potentially life-threatening infection. From 1979 to 1989 six cases of congenital lung cyst were diagnosed in utero by prenatal ultrasound and followed during pregnancy. Two of the six were not confirmed after birth because the mothers preferred an abortion. The remaining four cases were studied periodically during gestation by ultrasonography. At birth, the first infant developed respiratory distress and underwent urgent left upper lobectomy and left lower segmentectomy at age 18 hours. The other three underwent elective lobectomy at age 10 days, 3 months, and 7 months, respectively. The fourth infant had a normal chest x-ray and ultrasound at birth, and the congenital cysts were confirmed by computed tomography scan. The pathological diagnosis in all four cases was cystic adenomatoid malformation. In two cases, intraoperative measurement of pulmonary function demonstrated significant improvement after resection of the affected lobe. We conclude that congenital lung cysts can be accurately diagnosed by prenatal ultrasound "screening" as early as 18 to 24 weeks' gestation. Advantages of early diagnosis include the option of moving the mother and unborn child to a high-risk obstetrical center for urgent operation on the newborn infant if necessary. Otherwise, once the diagnosis is confirmed, surgical correction can be performed electively and safely before respiratory distress or pulmonary infection complicates the infant's growth and development.