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Biomedical subjects

R Boyle

Publications and source records attributed to R Boyle.

At least 19 recordsLinked to original sources

Cytoskeletal involvement during hypo-osmotic swelling and volume regulation in cultured chick cardiac myocytes.

The membrane skeleton in spherical cardiac myocytes subjected to hypo-osmotic challenge was examined by laser scanning confocal microscopy. A distinct cortical layer intimately localized under the plasmalemma was revealed for spectrin and actin (including filamentous actin and alpha-sarcomeric actin). Desmin filaments were abundant and in close contact with the plasmalemma. During swelling and subsequent regulatory volume decrease (RVD) the structural integrity of these cytoskeletal elements remained intact, and the close association between actin and plasmalemma persisted as confirmed by double immunolabeling. Subplasmalemmal beta-tubulin labeling was sparse. Hypo-osmotic conditions disrupted the microtubules and depolymerized tubulin. Neither pretreatment with taxol nor with colchicine, resulted in any effect on cell volume regulation. The present results show that actin, desmin, and spectrin contribute to a subplasmalemmal cytoskeletal network in spherical cardiac myocytes, and that this membrane skeleton remains structurally intact during swelling and RVD. It is suggested that the integrity of this membrane skeleton is important for stabilization of the plasmalemma and the membrane-integrated proteins during hypo-osmotic challenge, and that it may participate in the regulation of the cell volume.

Actins↗

International Guidelines for Neonatal Resuscitation: An excerpt from the Guidelines 2000 for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care: International Consensus on Science. Contributors and Reviewers for the Neonatal Resuscitation Guidelines.

The International Guidelines 2000 Conference on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiac Care (ECC) formulated new evidenced-based recommendations for neonatal resuscitation. These guidelines comprehensively update the last recommendations, published in 1992 after the Fifth National Conference on CPR and ECC. As a result of the evidence evaluation process, significant changes occurred in the recommended management routines for: * Meconium-stained amniotic fluid: If the newly born infant has absent or depressed respirations, heart rate <100 beats per minute (bpm), or poor muscle tone, direct tracheal suctioning should be performed to remove meconium from the airway. * Preventing heat loss: Hyperthermia should be avoided. * Oxygenation and ventilation: 100% oxygen is recommended for assisted ventilation; however, if supplemental oxygen is unavailable, positive-pressure ventilation should be initiated with room air. The laryngeal mask airway may serve as an effective alternative for establishing an airway if bag-mask ventilation is ineffective or attempts at intubation have failed. Exhaled CO(2) detection can be useful in the secondary confirmation of endotracheal intubation. * Chest compressions: Compressions should be administered if the heart rate is absent or remains <60 bpm despite adequate assisted ventilation for 30 seconds. The 2-thumb, encircling-hands method of chest compression is preferred, with a depth of compression one third the anterior-posterior diameter of the chest and sufficient to generate a palpable pulse. * Medications, volume expansion, and vascular access: Epinephrine in a dose of 0.01-0.03 mg/kg (0.1-0.3 mL/kg of 1:10,000 solution) should be administered if the heart rate remains <60 bpm after a minimum of 30 seconds of adequate ventilation and chest compressions. Emergency volume expansion may be accomplished with an isotonic crystalloid solution or O-negative red blood cells; albumin-containing solutions are no longer the fluid of choice for initial volume expansion. Intraosseous access can serve as an alternative route for medications/volume expansion if umbilical or other direct venous access is not readily available. * Noninitiation and discontinuation of resuscitation: There are circumstances (relating to gestational age, birth weight, known underlying condition, lack of response to interventions) in which noninitiation or discontinuation of resuscitation in the delivery room may be appropriate.

Blood Volume↗

Sensory processing in the vestibular nuclei during active head movements.

Many secondary vestibular neurons are sensitive to head on trunk rotation during reflex-induced and voluntary head movements. During passive whole body rotation the interaction of head on trunk signals related to the vestibulo-collic reflex with vestibular signals increases the rotational gain of many secondary vestibular neurons, including many that project to the spinal cord. In some units, the sensitivity to head on trunk and vestibular input is matched and the resulting interaction produces an output that is related to the trunk velocity in space. In other units the head on trunk inputs are stronger and the resulting interaction produces an output that is larger during the reflex. During voluntary head movements, inputs related to head on trunk movement combine destructively with vestibular signals, and often cancel the sensory reafferent consequences of self-generated movements. Cancellation of sensory vestibular signals was observed in all of the antidromically identified secondary vestibulospinal units, even though many of these units were not significantly affected by reflexive head on trunk movements. The results imply that the inputs to vestibular neurons related to head on trunk rotation during reflexive and voluntary movements arise from different sources. We suggest that the relative strength of reflexive head on trunk input to different vestibular neurons might reflect the different functional roles they have in controlling the posture of the neck and body.

Animals↗

Treatment of spit tobacco users with transdermal nicotine system and mint snuff.

The purpose of this study was to examine the effects of nicotine patch and mint snuff (a nonnicotine product) on craving, withdrawal symptoms, and treatment outcome. This study involved a 2 x 2 factorial design, with Active Nicotine Versus Placebo Patch as one of the factors and Mint Snuff Versus No Mint Snuff as the other factor. Spit tobacco users (N = 402, n = 100-101 in each condition) were randomly assigned to 1 of the 4 treatment conditions for a period of 10 weeks. Treatment outcome was measured up to 62 weeks. The results showed that the nicotine patch was effective in increasing short-term abstinence over the placebo patch and in reducing craving and withdrawal signs and symptoms from spit tobacco. Although mint snuff was not effective in enhancing treatment outcome, it reduced craving and withdrawal symptoms. No interaction effects were observed. At this time, the use of the nicotine patch and mint snuff should be primarily considered for the reduction of craving and withdrawal symptoms.

Administration, Cutaneous↗

Morphology of lumbar-projecting lateral vestibulospinal neurons in the brainstem and cervical spinal cord in the squirrel monkey.

The lateral vestibulospinal tract (LVST) is one of the major descending pathways controlling the extensor musculature of the body. To determine whether individual LVST neurons terminating in the lumbosacral spinal segments issue collaterals more rostrally to exert an influence of the cervical ventral horn intracellular recording and biocytin labeling techniques were used in the squirrel monkey. Only neurons monosynaptically related to the 8th nerve and antidromically identified to project below T12 were selected for study. The axon course through the brainstem and cervical spinal cord was examined in 37 LVST neurons. The average distance of recovered axon was 17.3 mm (4.5-31.7 mm). None could be antidromically activated from shocks applied to the rostral medial longitudinal fasciculus near the 3rd nuclei; and no collaterals were observed in the brainstem. Of the 37 neurons, only 1 axon issued a collateral to innervate the ventral horn, primarily in the region of the spinal accessory motoneurons; this single collateral provided a relatively minor input compared to that of LVST neurons terminating in the cervical cord. Thus, secondary, caudal-projecting LVST neurons represent a private, and mostly rapid, communication pathway between dorsal Deiters' nucleus and the motor circuits controlling the lower limbs and tail.

Animals↗

Membrane skeleton in cultured chick cardiac myocytes revealed by high resolution immunocytochemistry.

Distribution of cytoskeletal proteins with emphasis on the membrane-cytoskeleton interface was examined in cultured cardiac myocytes. Using specific antibodies recognizing alpha-sarcomeric actin, desmin, beta-tubulin, spectrin/alpha-fodrin and ankyrin, respectively, the cellular localization of these cytoskeletal proteins was detected by laser scanning confocal microscopy. In addition, the fine filamentous structure of these proteins was identified by combining silver-enhanced immunogold labelling with electron microscopy. The latter technique employed the sequence of quick-freezing, deep-etching and rotary shadowing of the specimens. Conventional transmission electron microscopy of the spherical cardiac myocytes revealed a filamentous submembranous layer, approximately 100 nm thick. Specific immunolabelling of alpha-sarcomeric actin and spectrin/alpha-fodrin as well as ankyrin was seen beneath the plasmalemma. A three-dimensional meshwork of spectrin/alpha-fodrin was shown. Numerous desmin filaments that exhibited a tortuous course throughout the cells were also observed running in parallel with the surface in the submembranous area, whereas beta-tubulin was infrequently detected in these areas. In conclusion, the present study shows that spherical cardiac myocytes contain a distinct and complex three-dimensional membrane skeleton. Major constituents of this distinct submembranous layer were spectrin/alpha-fodrin fibres as well as actin and desmin filaments.

Animals↗

Identification of head motions by central vestibular neurons receiving linear and angular input.

Most naturally occurring displacements of the head in space, due to either an external perturbation of the body or a self-generated, volitional head movement, apply both linear and angular forces to the head. The vestibular system detects linear and angular accelerations of the head separately, but the succeeding control of gaze and posture often relies upon the combined processing of linear and angular motion information. Thus, the output of a secondary neuron may reflect the linear, the angular, or both components of the head motion. Although the vestibular system is typically studied in terms of separate responses to linear and angular acceleration of the head, many secondary and higher-order neurons in the vestibular system do, in fact, receive information from both sets of motion sensors. The present paper develops methods to analyze responses of neurons that receive both types of information, and focuses on responses to sinusoidal motions composed of a linear and an angular component. We show that each neuron has a preferred motion, but a single neuron cannot code for a single motion. However, a pair of neurons can code for a motion by the relative phases of firing-rate modulation. In this way, information about motion is enhanced by neurons combining information about linear and angular motion.

Animals↗

Absence of demonstrable immune dysregulation in motor neuron disease.

Patients with motor neuron disease (MND) (n =33) free of infection were assessed for symptoms of autoimmunity and evidence of peripheral immune activation. Clinical features of autoimmune disease and antinuclear antibodies were notably absent in all patients. Compared with healthy controls, patients with MND had no significant difference in lymphocyte subsets (CD4/8 T cells, B and NK cells). Serum and whole blood endotoxin and phytohaemagglutinin stimulated levels of interferon gamma, granulocyte macrophage colony stimulating factor, interleukin (IL) 1beta, IL4, IL10, tumour necrosis factor alpha and soluble CD23 were no different between patients with MND and healthy controls. Our results confirm the absence of significant elevations of immune regulatory proteins in the peripheral circulation of patients with MND. Copyright 1999 Harcourt Publishers Ltd.

Journal Article↗

Firing behavior of vestibular neurons during active and passive head movements: vestibulo-spinal and other non-eye-movement related neurons.

The firing behavior of 51 non-eye movement related central vestibular neurons that were sensitive to passive head rotation in the plane of the horizontal semicircular canal was studied in three squirrel monkeys whose heads were free to move in the horizontal plane. Unit sensitivity to active head movements during spontaneous gaze saccades was compared with sensitivity to passive head rotation. Most units (29/35 tested) were activated at monosynaptic latencies following electrical stimulation of the ipsilateral vestibular nerve. Nine were vestibulo-spinal units that were antidromically activated following electrical stimulation of the ventromedial funiculi of the spinal cord at C1. All of the units were less sensitive to active head movements than to passive whole body rotation. In the majority of cells (37/51, 73%), including all nine identified vestibulo-spinal units, the vestibular signals related to active head movements were canceled. The remaining units (n = 14, 27%) were sensitive to active head movements, but their responses were attenuated by 20-75%. Most units were nearly as sensitive to passive head-on-trunk rotation as they were to whole body rotation; this suggests that vestibular signals related to active head movements were cancelled primarily by subtraction of a head movement efference copy signal. The sensitivity of most units to passive whole body rotation was unchanged during gaze saccades. A fundamental feature of sensory processing is the ability to distinguish between self-generated and externally induced sensory events. Our observations suggest that the distinction is made at an early stage of processing in the vestibular system.

Animals↗

Influence of surgical plugging on horizontal semicircular canal mechanics and afferent response dynamics.

Mechanical occlusion of one or more of the semicircular canals is a surgical procedure performed clinically to treat certain vestibular disorders and used experimentally to assess individual contributions of separate canals and/or otoliths to vestibular neural pathways. The present experiments were designed to determine if semicircular canal afferent nerve modulation to angular head acceleration is blocked by occlusion of the endolymphatic duct, and if not, what mechanism(s) might account for a persistent afferent response. The perilymphatic space was opened to gain acute access to the horizontal canal (HC) in the oyster toadfish, Opsanus tau. Firing rate responses of HC afferents to sinusoidal whole-body rotation were recorded in the unoccluded control condition, during the process of duct occlusion, and in the plugged condition. The results show that complete occlusion of the duct did not block horizontal canal sensitivity; individual afferents often exhibited a robust firing rate modulation in response to whole-body rotation in the plugged condition. At high stimulus frequencies (about >8 Hz) the average sensitivity (afferent gain; spikes/s per degrees /s of head velocity) in the plugged condition was nearly equal to that observed for unoccluded controls in the same animals. At low stimulus frequencies (about <0.1 Hz), the average sensitivity in the plugged condition was attenuated by more than two orders of magnitude relative to unoccluded controls. The peak afferent firing rate for sinusoidal stimuli was phase advanced approximately 90 degrees in plugged canals relative to their control counterparts for stimulus frequencies approximately 0.1-2 Hz. Data indicate that afferents normally sensitive to angular velocity in the control condition became sensitive to angular acceleration in the plugged condition, whereas afferents sensitive to angular acceleration in the control condition became sensitive to the derivative of acceleration or angular jerk in the plugged condition. At higher frequencies (>8 Hz), the phase of afferents in the plugged condition became nearly equal, on average, to that observed in controls. A three-dimensional biomechanical model of the HC was developed to interpret the residual response in the plugged condition. Labyrinthine fluids were modeled as incompressible and Newtonian; the membranous duct, osseous canal and temporal bone were modeled as visco-elastic materials. The predicted attenuation and phase shift in cupular responses were in close agreement with the observed changes in afferent response dynamics after canal plugging. The model attributes the response of plugged canals to labyrinthine fluid pressure gradients that lead to membranous duct deformation, a spatial redistribution of labyrinthine fluids and cupular displacement. Validity of the model was established through its ability to predict: the relationship between plugged canal responses and unoccluded controls (present study), the relationship between afferent responses recorded during mechanical indentation of the membranous duct and physiological head rotation, the magnitude and phase of endolymphatic pressure generated during HC duct indentation, and previous model results for cupular gain and phase in the rigid-duct case. The same model was adjusted to conform to the morphology of the squirrel monkey and of the human to investigate the possible influence of canal plugging in primates. Membranous duct stiffness and perilymphatic cavity stiffness were identified as the most salient model parameters. Simulations indicate that canal plugging may be the most effective in relatively small species having small labyrinths, stiff round windows, and stiff bony perilymphatic enclosures.

Afferent Pathways↗

Antenatal and preoperative genetic and clinical assessment in myotonic dystrophy.

The antenatal investigation of an obstetric patient with a history of myotonia is described. The smooth and striated muscle dysfunction in myotonic dystrophy renders these patients, as a group, liable to surgical correction and exposure to anaesthesia. A caesarean section is reported to illustrate the preferred timing of diagnosis and peripartum management. While regional anaesthesia is preferred, myotonic dystrophy is not a contraindication to general anaesthesia, provided risks are anticipated and steps taken to minimize complications.

Adult↗

Differential central projections of physiologically characterized horizontal semicircular canal vestibular nerve afferents in the toadfish, Opsanus tau.

Anatomical and neurophysiological studies were undertaken to examine the central projection pattern of physiologically characterized horizontal semicircular canal vestibular nerve afferents in the toadfish, Opsanus tau. The variations in individual response characteristics of vestibular nerve afferents to rotational stimulus provided a means of typing the afferents into descriptive classes; the afferents fell into a broad continuum across the spectrum from low-gain, velocity-sensitive to high-gain, acceleration-sensitive responses (Boyle and Highstein [1990b] J. Neurosci. 10:1557-1569; Boyle and Highstein [1990a] J. Neurosci. 10:1570-1582). In the present study, each afferent was typed as a low-gain, high-gain, or acceleration fiber during rotational or mechanical stimulation (Rabbitt et al. [1995] J. Neurophysiol. 73:2237-2260) and was then intracellularly injected with biocytin. The axons were reconstructed, and the morphology, synaptic boutons, and projection pattern of each axon were determined. The results indicated that the three descriptive classes of vestibular nerve afferents have unique as well as overlapping central projection patterns and destinations in the vestibular nuclei, with intranuclear parcellation in the anterior octavus, magnocellularis, tangentialis, posterior octavus, and descending octavus nuclei. In general, increased sensitivity and faster response dynamics were correlated with both a more extensive central projection and a progressive increase in morphological complexity. Low-gain, velocity-sensitive fibers were the simplest morphologically, with the fewest number of branches (n = 17) and shortest length (4,282 microm), and projections were confined to the middle portions of the vestibular nuclei. High-gain, velocity-sensitive fibers were morphologically more diverse than low-gain fibers, with a greater number of branches (n = 26), longer length (6,059 microm), 29% greater volume, and a more widespread projection pattern with projections to both the anterior and the middle portions of the vestibular nuclei. Acceleration fibers were morphologically distinct from low- and high-gain fibers, with more elaborate branching (n = 41), greatest overall length (17,370 microm) and volume (16% greater than high gains), and displayed the most extensive central projection pattern, innervating all vestibular nuclei except tangentialis. Thus, there are anatomically demonstrable differential central projections of canal afferents with different response dynamics within the vestibular complex of the fish.

Animals↗

Determinants of semicircular canal afferent response dynamics in fish.

Present results separate the relative contributions of semicircular canal biomechanics from hair cell/afferent biophysics in determining the amplitude and phase of afferent responses to sinusoidal motion of the head. Separation was achieved by combining electrical polarization of the endolymph with mechanical indentation of the canal limb to modulate the instantaneous firing rate of horizontal semicircular canal afferents. The electrical stimulus drives hair cell transduction currents via modulation of the Nernst-Planck potential, whereas the mechanical stimulus mimics head rotation and modulates the open probability of the transduction channels. Responses for electrical polarization therefore reflect post-transduction-current (PTC) mechanisms, and responses for mechanical stimulation include the additional influence of canal mechanics. Linear transfer functions defining individual afferent response dynamics were obtained for low levels of each stimuli and are reported in Bode form providing gain (spikes/s per micron or mV) and phase (deg re: peak stim) over the frequency range from 0.02 to 40 Hz. Combined results for electrical and mechanical stimuli distinguish the component of sensory signal processing carried out by canal mechanics from that carried out by the hair cell/afferent complexes. Individual afferents were categorized according to their response to the mechanical stimuli as low-gain velocity (LG), high-gain velocity (HG) or acceleration (A) sensitive, groups as originally defined by Boyle and Highstein to describe interafferent diversity present within the population. In contrast to the results for mechanical stimuli, all afferent groups exhibit nearly equal increases in gain and phase for increasing frequencies of electrical stimulation. Comparison of individual afferent responses for the two stimuli leads to the conclusion that the LG, HG, and A groups are distinguished primarily by diversity in the mechanical activation of associated hair cells and not by PTC mechanisms. Even though PTC processing does not contribute significantly to determining these groups, it is the primary determinant underlying high-frequency gain and phase enhancements observed in the population average. Comparison of mechanical and electrical responses also reveals the mechanical lower-corner responsible for phase enhancements and gain decreases in all afferents at low frequencies of mechanical stimulation (< 0.05 Hz). Results imply that LG afferents encode angular head velocity by canceling a phase lag and gain attenuation due to the mechanics with a phase lead and gain enhancement due to PTC mechanisms above approximately 0.2 Hz. In contrast, A group afferents encode angular head acceleration by combining high-frequency phase leads and gain enhancements present in both the mechanics and PTC mechanisms across the physiological frequency spectrum. HG afferents fall between these two extremes, and, other than the influence of the mechanical lower-corner, their response primarily reflects PTC processing.

Action Potentials↗

The effect of the pediatric clerkship on medical student attitudes toward pediatrics at 11 medical schools.

OBJECTIVES: To investigate how the pediatric clerkship affected student attitudes toward pediatrics, and to determine if correlations existed between changes in attitudes toward pediatrics and in ratings of certain aspects of the clerkship with an increased interest in a pediatric career. METHODS: A one-page survey measuring interest in a career in pediatrics and agreement or disagreement with seven statements about pediatrics was administered at the beginning and end of the pediatric clerkship at 11 medical schools for the 1992-1993 academic year. RESULTS: The proportion of students with a strong interest in a pediatric career increased from 6.7% before the clerkship to 15.2% after the clerkship (for women, 11% to 22%; for men, 4% to 11%). Attitudes toward pediatrics were more favorable at the end vs the beginning of the clerkship. The change that correlated best with change in interest in a pediatrics career was agreement that children are enjoyable to work with. Of the eight aspects of the clerkship rated, the patients worked with on the ward received the most positive mean score. The item that correlated best with increased career interest was a positive feeling toward the ward residents. CONCLUSION: The recent trend for women to have a greater interest in careers in pediatrics than men is continuing. Finding ways to make students more comfortable when they interact with children and improving the teaching skills of residents could improve recruitment of medical students into pediatrics.

Career Choice↗

Effects of irrelevant sounds on phonological coding in reading comprehension and short-term memory.

The effects of irrelevant sounds on reading comprehension and short-term memory were studied in two experiments. In Experiment 1, adults judged the acceptability of written sentences during irrelevant speech, accompanied and unaccompanied singing, instrumental music, and in silence. Sentences varied in syntactic complexity: Simple sentences contained a right-branching relative clause (The applause pleased the woman that gave the speech) and syntactically complex sentences included a centre-embedded relative clause (The hay that the farmer stored fed the hungry animals). Unacceptable sentences either sounded acceptable (The dog chased the cat that eight up all his food) or did not (The man praised the child that sight up his spinach). Decision accuracy was impaired by syntactic complexity but not by irrelevant sounds. Phonological coding was indicated by increased errors on unacceptable sentences that sounded correct. These errors rates were unaffected by irrelevant sounds. Experiment 2 examined effects of irrelevant sounds on ordered recall of phonologically similar and dissimilar word lists. Phonological similarity impaired recall. Irrelevant speech reduced recall but did not interact with phonological similarity. The results of these experiments question assumptions about the relationship between speech input and phonological coding in reading and the short-term store.

Adolescent↗