PubMed HealthSearch

Biomedical subjects

J T Murphy

Publications and source records attributed to J T Murphy.

At least 19 recordsLinked to original sources

A comparison of the myocardial metabolic and haemodynamic changes produced by propofol-sufentanil and enflurane-sufentanil anaesthesia for patients having coronary artery bypass graft surgery.

The purpose of this study was to compare propofol-sufentanil with enflurane-sufentanil anaesthesia for patients undergoing elective coronary artery bypass graft (CABG) surgery with respect to changes in (1) haemodynamic variables; (2) myocardial blood flow and metabolism; (3) serum cortisol, triglyceride, lipoprotein concentrations and liver function; and (4) recovery characteristics. Forty-seven patients with preserved ventricular function (ejection fraction greater than 40%, left ventricular end diastolic pressure less than or equal to 16 mmHg) were studied. Patients in Group A (n = 24) received sufentanil 0.2 microgram.kg-1 and propofol 1-2 mg.kg-1 for induction of anaesthesia which was maintained with a variable rate propofol (50-200 micrograms.kg-1.min-1) infusion and supplemental sufentanil (maximum total 5 micrograms.kg-1). Patients in Group B (n = 23) received sufentanil 5 micrograms.kg-1 for induction of anaesthesia which was maintained with enflurane and supplemental sufentanil (maximum total 7 micrograms.kg-1). Haemodynamic and myocardial metabolic profiles were determined at the awake-sedated, post-induction, post-intubation, first skin incision, post-sternotomy, and pre-cardiopulmonary bypass intervals. Induction of anaesthesia produced a larger reduction in systolic blood pressure in Group A (156 +/- 22 to 104 +/- 20 mmHg vs 152 +/- 26 to 124 +/- 24 mmHg; P less than 0.05). No statistical differences were detected at any other time or in any other variable including myocardial lactate production (n = 13 events in each group), time to tracheal extubation and time to discharge from the ICU. We concluded that, apart from hypotension on induction of anaesthesia, propofol-sufentanil anaesthesia produced anaesthetic conditions equivalent to enflurane-sufentanil anaesthesia for CABG surgery.

Adult

Single unit analysis of the human ventral thalamic nuclear group. Activity correlated with movement.

During neurosurgical operations for the relief of movement disorders, single thalamic neurons (n = 107) were identified with activity which was related to verbally cued active movements (movement-related cells). The activity of each neuron was examined during different contralateral movements in order to determine the movement which was associated with the most consistent and pronounced change in firing rate (the optimal response). The optimal response was determined by analysis of histograms of neuronal activity which were constructed by using the onset of EMG activity to synchronize successive repetitions of the active movement. Movement-related cells exhibited optimal responses associated with such movements as making a fist, extension or flexion of the wrist, flexing or extending the elbow, pointing with the entire upper extremity, extending the tongue and lifting the leg. Most movement-related cells recorded in a single parasagittal plane in an individual patient had optimal responses related to movements involving the same part of the body. Movement-related cells were classified into those that were activated in response to somatosensory stimulation (combined cells, n = 20) and those which were not (voluntary cells, n = 87). Combined cells were activated in advance of EMG activity during active movement and so could be distinguished from cells responding only to sensory stimulation (sensory cells). Movement-related cells (combined and voluntary cell types) were located anterior to sensory cells and tended to show a mediolateral somatotopic organization parallel to that of sensory cells with cutaneous receptive fields. Combined cells responded to somatosensory stimulation of the same part of the body as that involved in the active movement related to the optimal response of the cell. Combined cells responding to passive movements of a joint always had their optimal response during active movement about the same joint. The activity of combined cells during parkinsonian tremor may clarify the role of sensory feedback in tremor.

Electric Stimulation

Binding of transcription factors to the promoter of the human U1 RNA gene studied by footprinting.

The promoter structure of the known small nuclear RNA (snRNA) genes contains two major effectors of transcriptional activity: a proximal sequence element and a distal sequence element. In addition to these two functional elements (called elements B and D), the human U1 snRNA gene contains at least three minor elements (elements A, C, and E) that contribute to overall transcriptional efficiency (Murphy, J.T., Skuzeski, J.M., Lund, E., Steinberg, T.H., Burgess, R.R., and Dahlberg, J.E. (1987) J. Biol. Chem. 262, 1795-1803). To elucidate further the function of these transcription elements, we carried out a computer search to look for sequences in the U1 gene homologous to known transcription factor consensus sequences. Where such homology was found, DNase I and MPE-Fe(II) (methidiumpropyl-EDTA-Fe(II] footprinting was employed to study the interactions of these promoter regions with proteins partially purified from extracts of HeLa cells or human placenta. Footprints were observed over element D (the distal element) corresponding to sequences homologous to the octanucleotide binding protein (OCTA) and activator protein 1 (AP1). Protection was also observed over element B (the proximal element) corresponding to possible sites for stimulatory protein 1 (Sp1), enhancer core, major late transcription factor (MLTF), and a U1-specific transcription factor. Prior to this study, no specific transcription factor footprints had been observed over proximal elements of any snRNA gene. Footprints were also found over elements A and E. The results of the computer search and the footprinting are discussed in light of what is known about snRNA promoter activity.

Base Sequence

Single-unit analysis of the human ventral thalamic nuclear group: somatosensory responses.

1. We have studied the functional and somatotopic properties of 531 single mechanoreceptive thalamic neurons in humans undergoing stereotactic surgery for the control of movement disorders and pain. The majority of these somatosensory cells had small receptive fields (RFs) and were activated in a reproducible manner by mechanical stimuli applied to the skin or deep tissues. These neurons, which we termed "lemniscal," could be further classified into those responding to stimulation of cutaneous (76% of lemniscal sensory cells) or deep (24%) structures. 2. The incidence of neurons having cutaneous or mucosal RFs in the perioral region, thumb, and fingers (66%) was much higher than that of neurons having RFs elsewhere on the body. Most of the deep cells were activated by movements of and/or mechanical stimuli delivered to muscles or tendons controlling the elbow, wrist, and fingers. 3. Sequences of cells spanning several millimeters in the parasagittal plane often exhibited overlapping RFs. However, RFs changed markedly for cells separated by the same distances in the mediolateral direction. This suggests that the cutaneous somatotopic representation of each region of the body is organized into relatively thin sheets of cells oriented in the parasagittal plane. 4. By comparing neuronal RFs in different parasagittal planes in thalamus of individual patients we have identified a mediolateral representation of body surface following the sequence from: intraoral structures, face, thumb through fifth finger to palm, with forearm and leg laterally. 5. Along many trajectories in the parasagittal plane the sequence of cells with overlapping RFs was interrupted by another sequence of cells with RFs corresponding to a different body region. The RFs of the intervening sequence characteristically represented body regions known to be located more medially in thalamus (see 3 above). These findings could be explained if the lamellae postulated above were laterally convex. 6. Cells responding to deep stimulation (deep cells) could be further classified into those responding to joint movement (63%), deep pressure (15%), or both (22%). Deep cells were found usually at the anterior-dorsal border and sometimes at the posterior border of the region containing cells responding to cutaneous stimuli. Although there was some overlap in the RFs, deep cells representing wrist were found medial to those representing elbow, and both of these were found medial to cells representing leg.(ABSTRACT TRUNCATED AT 400 WORDS)

Brain Mapping

Methods for microstimulation and recording of single neurons and evoked potentials in the human central nervous system.

An apparatus and technique are described for microstimulation and recording of both slow wave and single neuron (single unit) activities during functional stereotaxic procedures. This method facilitates microstimulation and evoked potential and single unit analysis which, in combination, provide optimum definition of stereotaxic targets in the treatment of functional disorders of the human central nervous system.

Brain

Single unit analysis of the human ventral thalamic nuclear group: correlation of thalamic "tremor cells" with the 3-6 Hz component of parkinsonian tremor.

Although cells firing at tremor frequency, called "tremor cells" (Guiot et al., 1962), have often been recorded in the thalamus of parkinsonian patients, the extent of correlation between these spike trains and tremor has rarely been assessed quantitatively. This paper describes spectral cross-correlation functions calculated between the activity of "tremor cells" and electromyogram (EMG) signals recorded from several muscles in the contralateral arm. The power occurring in the spike train at tremor frequency was described in absolute terms by the spike autopower, and in relation to the average for all spectral components by the spike autopower signal-to-noise ratio (spike autopower SNR). The probability of significant cross-correlation between the thalamic spike train and EMG at tremor frequency was assessed by the coherence at tremor frequency. Autopower spectra of the activity of many of these cells exhibited a concentration of power at tremor frequency, indicated by spike autopower SNRs as high as 18. Of the EMG signals studied, signals recorded from finger flexors were most often significantly correlated at tremor frequency. Significant correlation between the thalamic spike train and finger flexor EMG activity was found in 34% of cells analyzed. Tremor frequency coherence was significantly correlated with tremor frequency spike autopower (r = 0.46, p less than 0.0001) and spike autopower SNR (r = 0.533, p less than 0.0001). The proportion of cells with a spike autopower SNR greater than 2 that were significantly correlated with finger flexor EMG activity was greater than that of cells with a spike autopower SNR of less than 2 (p less than 0.001; chi-square). Therefore, cells exhibiting a large amount of power at tremor frequency were those best correlated with EMG activity during tremor. Some of these cells may be involved in the generation of tremor.

Action Potentials

Functional elements of the human U1 RNA promoter. Identification of five separate regions required for efficient transcription and template competition.

We have determined the structure of the human U1 snRNA promoter by microinjection of several mutant U1 templates into Xenopus laevis oocytes. These deletion templates were assayed for their ability to express mature U1 RNA and for their ability to compete for limiting transcription factors. We have mapped five separate regions, called promoter elements A, B, C, D, and E. Element A, located between positions -8 and -50, stimulates transcription 3- to 5-fold increases the accuracy of initiation; element B (between -50 and -80) fixes the site of initiation and stimulates transcription greater than 100-fold; element C (upstream of -129) increases the efficiency of element B 3- to 5-fold; element D (between -191 and -231) is an orientation-independent and partially position-independent enhancer responsible for a 100-fold stimulation of transcription; element E (between -335 and -393) increases the ability to compete with other snRNA genes 4-fold. All five promoter elements are required for effective competition with the wild-type U1 promoter suggesting that binding of transcription factor(s) to the complex is cooperative. The U1 RNA and some mRNA gene transcription complexes appear to share one or more transcription factors.

Animals

Interaction between neurons in precentral cortical zones controlling different joints.

The relationship of the strength of interaction between precentral cortical neurons and their distance of separation during active reaching movements was studied in adult primates. Chronic unit recording experiments with two independent microelectrodes were performed in the left precentral forearm area of monkeys trained to execute reaching movements with the right arm in response to a visual cue. Neurons were identified by the joint actions produced by intracortical microstimulation. Cross-correlation analysis was employed to assess the strength of interaction between units. Unit pairs which exhibited the highest strength were recorded by the same electrode. For unit pairs derived from separate electrodes, the incidence and strength of interaction fell as the separation between the units was increased. Neurons identified by intracortical microstimulation as controlling the same or contiguous joints tended to interact with each other with much higher probability than did those neurons identified as controlling non-contiguous joints. When the direction of flow of information was assessed, these was a preferential flow from neurons controlling proximal joints to those controlling distal ones. These results are consistent with recent findings of tight kinematic coupling between contiguous joints and the observation of proximal-to-distal sequence of activation at the neuronal and electromyogram levels during voluntary movement.

Animals

Adult onset systemic carnitine deficiency: favorable response to L-carnitine supplementation.

We report the case of a patient who at age 39 first developed an episode of muscle weakness and transient ketoacidosis with biopsy proven fatty infiltration of the liver. Over the next several years, myopathy ensued; biopsy revealed extensive deposition of lipid globules in type 1 muscle fibres. Further investigations established the diagnosis of systemic carnitine deficiency (SCD) with skeletal muscle, hepatic, and cardiac involvement. The patient has benefited from L-carnitine supplementation. Our case represents an unusually late onset of SCD and highlights the necessity, when appropriate, of a high index of suspicion of this rare but treatable disorder.

Carnitine

Selection of the optimal lesion site for the relief of parkinsonian tremor on the basis of spectral analysis of neuronal firing patterns.

Techniques for quantitatively describing the firing properties of neurons have been used to identify thalamic cells with a firing pattern which is correlated with EMG activity during tremor. By locating these cells relative to the anterior border of the somatosensory nucleus and the anterior commissure-posterior commissure line, it may be possible to select the optimal lesion site for the relief of parkinsonian tremor on a rational rather than an empirical basis.

Humans

Evoked potentials from passive elbow movements. II. Modification by motor intent.

Subjects were instructed to remain passive or to react to a forearm perturbation by opposing the imposed movement. Evoked potentials (EPs) were recorded at 8 scalp sites in both conditions. In the React condition, reflexes were observed in the EMG (mean onsets of 67 and 81 msec) and the EP was modified. Source derivation techniques revealed that the earliest cortical response (31 msec) across the central sulcus was not changed. Therefore the intention to react did not seem to affect afferent transmission to the primary sensorimotor cortex. Two periods of modulation were observed. In both, parietal and frontal potentials were modulated together, prior to the reflex components. After 70 msec, the pattern of potential gradients which occurred in the Passive case was accelerated and intensified in the React condition. The overall effect was to focus a larger zone of negativity over motor cortex at the time of triggered EMG output (109 msec). The earlier changes in cortical activity could be causally related to the appearance of the late stretch reflex. Since parietal and frontal areas were principally involved and not the motor area, it is suggested that the former exert a modulatory influence on spinal and brain-stem reflex centres.

Elbow

Measurements of human forearm viscoelasticity.

In human subjects, stiffness of the relaxed elbow was measured by three methods, using a forearm manipulandum coupled to a.d.c. torque motor. Elbow stiffness calculated from frequency response characteristics increased as the driving amplitude decreased. Step displacements of the forearm produced restoring torques linearly related to the displacement. The stiffness was very similar to that calculated from natural frequencies at amplitudes above 0.1 rad. Thirdly, elbow stiffness was estimated from brief test pulses, 120 ms in duration, by mathematically simulating the torque-displacement functions. Stiffness values in the limited linear range (under +/- 0.1 rad) were higher than in the linear range of the first two methods. A major component of elbow stiffness appears to decay within 1 s. The coefficients of viscosity determined from the simulation were, however, very similar to those calculated from the frequency response. Test pulse simulation was then used to determine joint impedance for different, actively maintained elbow angles. Joint stiffness and viscosity increased with progressive elbow flexion.

Adult

Properties of visual cue responses in primate precentral cortex.

Monkeys were trained to perform a visuomotor task involving the alignment of a cursor over a vertical target line on a videomonitor by flexion or extension movements of the wrist. The forelimb area of the contralateral precentral cortex was thoroughly explored during the task. Intracortical microstimulation was employed to classify the forelimb region into wrist flexion--extension and non-wrist flexion--extension populations. Unit recording revealed an initial response to the cue for movement, viz. the appearance of the cursor and target line on the videomonitor, while visual signals not related to the task failed to evoke any response. The mean latency of these visual cue responses was approximately 150 ms. A great majority of the responses (96%) were bidirectional in character, in that they did not correlate with the directional information embedded in the visual cue, nor were they good predictors for the direction or timing of the subsequent movement. They were uniformly distributed in both the wrist and non-wrist regions of the forelimb area; the non-forelimb areas were devoid of the cue response. Further, when the variability of response to the visual cue for the wrist and non-wrist populations was compared, no significant difference was observed. These observations are consistent with an interpretation that the visually triggered cue responses provide a generalized activation over the task-related area of precentral cortex, paving the way for later and more specific activations leading to the execution of the task.

Animals

The selected use of ultrasound mammography to improve diagnostic accuracy in carcinoma of the breast.

Our initial experience with diagnostic ultrasound mammography (UM) showed it to be of high diagnostic accuracy and improved specificity when compared with x-ray mammography (XRM) in certain categories of patients. To evaluate this modality further, we reviewed our experience with 600 consecutive patients who underwent ultrasound mammography as part of their initial evaluation for breast disease. Five categories of patients were reviewed: I: age 35 or less--129; II: DY or P-2 pattern on XRM--174; III: negative XRM but symptoms requiring additional evaluation--81; IV: high risk remaining breast in patients previously having mastectomy--48; V: refusal of repeat XRM because of pregnancy, lactation, or fear of radiation exposure--168. Fifty-five solid lesions were diagnosed, including 36 carcinomas. Seventeen of these were not diagnosed on x-ray mammography, giving an improved pick-up of carcinoma in this overall group of 2.83%. Of particular interest was that, of the 27 carcinomas that were found in the group having XRM, 8 or 29.6% were missed on that modality alone. Five of these (62.5%) were patients having a DY pattern. All patients have been followed carefully and re-examined at 3-month intervals, with no evidence of a false negative examination. Overall, we feel diagnostic ultrasound mammography is a valuable adjunct to x-ray mammography and recommend its continued use in selected groups of patients where it has a superior diagnostic accuracy over x-ray mammography alone.

Adolescent

Evoked potentials from passive elbow movements. I. Quantitative spatial and temporal analysis.

Evoked potentials following perturbations of the forearm were recorded monopolarly at 8 scalp sites. Successive 10 msec bins of individual EPs were compared across subjects to determine intervals of consistent potential change. From this analysis it was possible to objectively sort subjects into two subpopulations with different common wave forms. Spatial vectors (potential gradient between two adjacent leads) were computed as well as Laplacian derivatives, to identify electrodes closest to source activity. Subsequently, temporal derivatives of the vectors were computed to define the timing of statistically significant response phases. To more precisely localize the largest potential gradients, component vectors (or their derivatives) in the Laplacians were resolved algebraically on a scaled representation of the scalp. Convergence of these resultant vectors from adjacent areas, identified zones of significant potential change which corresponded to known somatosensory areas. The two subpopulations had initial responses of similar topography localized to the central sulcal region. Subsequently, for one group the area of activated cortex expanded to include posterior parietal and more frontal areas. Prestimulus negative potential shifts had different distributions for the two groups and are described in relation to the poststimulus differences.

Adult

Cross correlation studies in primate motor cortex: synaptic interaction and shared input.

Awake, unrestrained monkeys were trained to reach out with the forelimb and touch a button. Extracellular spike trains were recorded from pairs of neurons in contralateral precentral cortex with the same or separate microelectrodes. The neurons were located in the same or different functional columns as defined by intracortical microstimulation and passive sensory stimulation. Cross correlation analysis showed patterns consistent with synaptic excitation and/or inhibition between members of the cell pairs during the voluntary movement. The strength of correlation was inversely related to distance between columns, with the strongest correlations found between cells within the same column. Inhibitory correlations were virtually restricted to cell pairs within a single column. Temporal analysis showed that direct synaptic interaction and shared input patterns could be clearly distinguished in this physiologic setting. Spatial analysis indicated that shared input was concentrated among columns in the same and adjacent joint controlling zones as well as within a single column. No directional preference of shared input was present, a finding which was consistent with the observed nested organization of the forelimb area.

Action Potentials