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Biomedical subjects

J T Murphy

Publications and source records attributed to J T Murphy.

At least 37 records · Page 2Linked to original sources

Randomized trial comparing intermittent antegrade warm blood cardioplegia with multidose cold blood cardioplegia for coronary artery bypass.

Forty patients were randomized to receive antegrade multidose warm (WBC) or cold blood cardioplegia (CBC) during coronary artery bypass. Cardioplegia was infused at a predetermined dose every 10 min during cardioplegia arrest and core temperature was maintained at 37 degrees C in both groups during extracorporeal circulation. Patient profiles were similar in the two groups. Cardiac index, left ventricular stroke work index, and myocardial oxygen consumption were measured before bypass and during the first 7 h of reperfusion. There was no significant difference in myocardial metabolic and function recovery, the incidence of myocardial infarction, low cardiac output or death. Our data suggests that similar protection is provided with the two techniques of myocardial protection.

Coronary Artery Bypass↗

Renal autotransplantation after horseshoe kidney injury: a case report and literature review.

We present a patient with lap seatbelt trauma to a previously unsuspected horseshoe kidney. Preoperative single film intravenous pyelography did not suggest the presence of this renal anomaly or define the extent of renal injury. Because of the severity of the injury, nephrectomy was life-saving, but inadvertently rendered the patient anephric. Recognition of horseshoe kidney anatomy, microvascular back-bench reconstruction, and renal autotransplantation allowed the salvage of both the patient and her renal function.

Accidents, Traffic↗

Continuous fluorescence assay of phytochrome assembly in vitro.

Incubation of recombinant apophytochrome with the phycobiliprotein chromophore precursor phycoerythrobilin produces a covalent adduct that exhibits a fluorescence excitation maximum at 576 nm and an emission maximum at 586 nm. Using these fluorescence parameters, we have developed a kinetic assay for quantitative analysis of the assembly of the plant photoreceptor phytochrome in real time. Kinetic measurements performed with different phycoerythrobilin concentrations confirm that bilin attachment to apophytochrome involves two steps, an initial formation of a reversible non-covalent complex followed by thioether bond formation. The kinetic constants for both steps of phycoerythrobilin attachment to apophytochrome were estimated with this assay. Methodology for determining the kinetic constants for the assembly of both the natural phytochrome chromophore precursor, phytochromobilin, and the analog phycocyanobilin is also described. Since the latter two bilins yield covalent, nonfluorescent adducts with apophytochrome, their co-incubation with phycoerythrobilin reduces the rate of formation of the fluorescent phycoerythrobilin adduct in an irreversible, competitive manner. Competition experiments were also performed with biliverdin, a structurally related bilin which does not form a covalent adduct with apophytochrome. Such measurements show that biliverdin reversibly binds to apophytochrome with a submicromolar binding constant, an affinity which is very similar to that of phytochromobilin. The utility of this fluorescence assay for identification of novel inhibitors of phytochrome assembly and for characterization of the structural features of both bilin and apophytochrome necessary for photoreceptor assembly is discussed.

Apoproteins↗

Pediatric grease burn injury.

OBJECTIVES: To evaluate the incidence and severity of grease and oil burns in children and to discuss prevention. DESIGN: All pediatric patients admitted with hot grease burns were compared with the general pediatric burn population. SETTING: All admissions to a regional burn center during a 20-year period were reviewed using a computerized database. PATIENTS: Eight thousand three hundred sixteen patients with acute burn injuries were admitted. Children less than 15 years old accounted for 31.9% of this population (2651 patients). Two hundred fifteen children had burns caused by hot grease or oil. INTERVENTIONS: Sixty-nine patients (32%) in the pediatric grease burn group were admitted to the intensive care unit. Thirteen patients (6%) required intubation, and six (46%) eventually required tracheostomy. Sixty-three patients (29.3%) required operative procedures for wound care. MAIN OUTCOME MEASURES: Grease burn patients had a significantly higher incidence of full-thickness burns, wound infection, and burns involving the face, neck, chest, and arms but lower mortality compared with the general pediatric burn population. Fifty percent of grease burns were caused by home deep fryers. RESULTS: There was no difference between the groups regarding age, sex, or ethnic distribution, size of injury, length of hospitalization, number of intensive care unit admissions, pulmonary infections, operative procedures, or mechanical ventilator requirements. CONCLUSIONS: Grease burns often result in long-lasting, disfiguring, and debilitating injuries. Home deep fryers are frequently involved in these injuries. Careful use of these appliances is mandatory. Increased public awareness is vital to this effort.

Adolescent↗

Myocardial metabolic and hemodynamic changes during propofol anesthesia for cardiac surgery in patients with reduced ventricular function.

This study examined the hypothesis that the use of propofol for induction and maintenance of anesthesia in patients with reduced ejection fraction (< 0.5) undergoing coronary artery revascularization would not be associated with a greater degree or incidence of myocardial ischemia as compared to patients receiving a moderate dose sufentanil-enflurane anesthetic technique. Two groups of patients were assigned randomly to receive one of two propofol anesthetic regimes. Group A (n = 21) received propofol 1-2 mg/kg as the induction drug and sufentanil 0.03 micrograms.kg-1.min-1 (fixed rate) plus propofol 50-200 micrograms.kg-1.min-1 (variable rate) infusions for maintenance of anesthesia. Group B (n = 21) received sufentanil 5 micrograms/kg for induction and propofol 50-200 micrograms.kg-1.min-1 (variable rate) infusion for maintenance of anesthesia. For comparison, a third group (Group C, n = 18) was studied subsequently. This group received sufentanil 5 micrograms/kg for induction of anesthesia which was maintained with enflurane. Adverse hemodynamic changes (hypertension, tachycardia) were managed by additional propofol (Groups A and B), sufentanil (Group C), or vasopressors (hypotension). Hemodynamic and myocardial metabolic profiles were measured when awake and sedated and at postinduction, postintubation, postincision, poststernotomy, and precardiopulmonary bypass times. Ischemia was assessed by measuring myocardial lactate production. The incidence of myocardial lactate production was reduced in Group B as compared to Group C (Group A, 45/126; Group B, 23/126; Group C, 58/107; P < 0.05). Myocardial lactate flux declined in all groups as surgery progressed; but apart from the reduction in flux (indicative of increased ischemia) noted in Group C versus Group B postinduction, no between-group differences were detected.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

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↗