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Biomedical subjects

C H Brown

Publications and source records attributed to C H Brown.

At least 37 records · Page 2Linked to original sources

A technique for distal tibial bone graft for arthrodesis of the foot and ankle.

Hindfoot and forefoot arthrodeses procedures are commonly performed using autogenous bone graft harvested from the distal tibia. A new technique is described for obtaining cancellous bone graft from the distal tibia using a bone graft harvesting system specifically designed to obtain morsellized material through a small incision site. The use of this device in association with low dose fluoroscopy and backfilling of the defect with osteoconductive synthetic graft material is also discussed.

Ankle↗

Revision anterior cruciate ligament surgery.

An increasing number of revision ACL reconstructions are being performed each year. Revision ACL surgery is challenging and cannot be approached in the same manner as primary ACL surgery. Successful revision ACL surgery requires a detailed history, a comprehensive physical examination, appropriate radiologic studies, and careful preoperative planning. The results of revision ACL surgery do not equal the results of primary ACL surgery, and this should be explained to the patient prior to surgery. In order to avoid repeating errors that led to failure of the primary reconstruction, the etiology of the primary failure must be clearly understood before proceeding with the revision procedure. Although graft failure is the most common reason for failure of the original reconstruction and revision surgery, other non-graft-related problems, such as loss of motion, extensor mechanism dysfunction, and degenerative arthritis, can also result in an unsatisfactory outcome and residual complaints. Errors in surgical technique, specifically nonanatomic graft placement and failure to address associated ligamentous injuries at the time of the original procedure, are responsible for graft failures in most reported series. Preoperative planning must address the issues of graft selection, skin incisions, hardware removal, tunnel placement, graft fixation, and associated ligamentous injuries. Loss of motion and in some cases enlarged bone tunnels may require a staged approach. Because of the weaker initial graft fixation, laxity of secondary restraints, the potential need to address associated ligamentous injuries, and the presence of more significant articular cartilage changes, an accelerated rehabilitation program is inappropriate in most revision cases. Successful revision ACL surgery requires a motivated and compliant patient, a well thought out plan, and an experienced surgeon who is knowledgeable and proficient with a variety of different surgical techniques, graft sources, and graft fixation techniques.

Anterior Cruciate Ligament↗

Physiological pathways regulating the activity of magnocellular neurosecretory cells.

Magnocellular oxytocin and vasopressin cells are among the most extensively studied neurons in the brain; their large size and high synthetic capacity, their discrete, homogeneous distribution and the anatomical separation of their terminals from their cell bodies, and the ability to determine their neuronal output readily by measurements of hormone concentration in the plasma, combine to make these systems amenable to a wide range of fundamental investigations. While vasopressin cells have intrinsic burst-generating properties, oxytocin cells are organized within local pattern-generating networks. In this review we consider the rôle played by particular afferent pathways in the regulation of the activity of oxytocin and vasopressin cells. For both cell types, the effects of changes in the activity of synaptic input can be complex.

Afferent Pathways↗

Proximal impact of two first-grade preventive interventions on the early risk behaviors for later substance abuse, depression, and antisocial behavior.

We assessed the immediate effects of two universal, first-grade preventive interventions on the proximal targets of poor achievement, concentration problems, aggression, and shy behaviors, known early risk behaviors for later substance use/abuse, affective disorder, and conduct disorder. The classroom-centered (CC) intervention was designed to reduce these early risk behaviors by enhancing teachers' behavior management and instructional skills, whereas the family-school partnership (FSP) intervention was aimed at improving parent-teacher communication and parental teaching and child behavior management strategies. Over the course of first and second grades, the CC intervention yielded the greatest degree of impact on its proximal targets, whereas the FSP's impact was somewhat less. The effects were influenced by gender and by preintervention levels of risk. Analyses of implementation measures demonstrated that greater fidelity to the intervention protocols was associated with greater impact on behavior ratings and on achievement scores, thus providing some evidence of specificity in the effect of the interventions.

Baltimore↗

Principles for designing randomized preventive trials in mental health: an emerging developmental epidemiology paradigm.

An emerging population-based paradigm is now being used to guide the design of preventive trials used to test developmental models. We discuss elements of the designs of several ongoing randomized preventive trials involving reduction of risk for children of divorce, for children who exhibit behavioral or learning problems, and for children whose parents are being treated for depression. To test developmental models using this paradigm, we introduce three classes of design issues: design for prerandomization, design for intervention, and design for postintervention. For each of these areas, we present quantitative results from power calculations. Both scientific and cost implications of these power calculations are discussed in terms of variation among subjects on preintervention measures, unit of intervention, assignment, balancing, number of pretest and posttest measures, and the examination of moderation effects.

Bias↗

Kappa-opioid receptor activation inhibits post-spike depolarizing after-potentials in rat supraoptic nucleus neurones in vitro.

Endogenous agonists acting at kappa-opioid receptors modulate the discharge activity of hypothalamic supraoptic nucleus vasopressin cells in vivo. Phasic activity in vasopressin cells is known to depend critically on intrinsic mechanisms involving post-spike depolarizing after-potentials and we hypothesized that inhibition of phasic bursting by an endogenous kappa-agonist may result from reducing the magnitude of depolarizing after-potentials. To investigate this possibility, intracellular sharp electrode recordings were obtained from supraoptic nucleus cells impaled in superfused explants of rat hypothalamus. Bath application of the selective kappa-agonist, U50,488H (0.1-1 microM), decreased the spontaneous firing rate of magnocellular neurosecretory cells (by 94. 0+/-4.5% at 1 microM, mean+/-SEM; P = 0.02, n = 4). U50,488H did not alter membrane potential (0.9+/-0.8 mV hyperpolarization at 1 microM, P = 0.17, n = 8) or input resistance (11.0+/-4.5% increase at 1 microM, P = 0.09, n = 5). U50,488H (0.1 and 1 microM, both n = 5) reduced depolarizing after-potential amplitude (by 29.9+/-9.3 and 78.0+/-10. 6%, respectively, P<0.001) in eight cells in which the baseline membrane potential was kept constant by dc-current injection and in which a depolarizing after-potential was evoked every 25-40 s by a brief (40-80 ms) train of 3-6 action potentials (the number of spikes in the trains was kept constant for each cell). Thus, kappa-opioid receptor activation reduces depolarizing after-potential amplitude in supraoptic nucleus cells and this may underlie the reduction in burst duration of vasopressin cells caused by an endogenous kappa-agonist in vivo.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Chronic central infusion of growth hormone secretagogues: effects on fos expression and peptide gene expression in the rat arcuate nucleus.

Growth hormone (GH) secretagogues induce GH release, in part, by direct actions upon anterior pituitary somatotropes and, in part, by actions upon the neuroendocrine circuitry that regulates GH secretion. In particular, acute systemic administration of GH secretagogues results in increased neuronal activity and Fos protein expression in the arcuate nucleus of the hypothalamus. Prolonged administration of GH secretagogues has been reported to have long-lasting effects upon GH release, promoting increased pulsatile secretion. Here, we investigated how chronic central infusion of GH secretagogues affects the response of arcuate nucleus neurons to acute systemic administration of GH secretagogues. In male rats, after central infusion of GH secretagogues for 5 days, there was no sustained expression of Fos in the arcuate nucleus, no significant induction of Fos expression in response to acute GH secretagogue challenge, and a greatly attenuated secretion of GH in response to acute GH secretagogue challenge, all reflecting loss of funtional responsiveness to GH secretagogues. In situ hybridisation revealed that, in the arcuate nucleus of GH secretagogue-infused rats, mRNA levels for GH-releasing hormone, neuropeptide Y and somatostatin were not different than in saline-infused animals. However, somatostatin mRNA levels in the periventricular nuclei of GH secretagogue-infused rats were significantly higher than those of saline-infused rats, indicating that this nucleus may play an important role in mediating the effects of chronic GH secretagogue administration.

Animals↗

Hamstring tendon grafts for reconstruction of the anterior cruciate ligament: biomechanical evaluation of the use of multiple strands and tensioning techniques.

BACKGROUND: Our hypothesis that multiple, equally tensioned strands of hamstring graft used for reconstruction of the anterior cruciate ligament are stronger and stiffer than ten-millimeter patellar ligament grafts was tested biomechanically with use of tendons from cadavera. METHODS: In the first part of the study, we measured the strength and stiffness of one, two, and four-strand hamstring grafts, from fresh-frozen cadaveric knees, that had been tensioned equally when clamped. In the second part of the study, we compared four-strand grafts to which tension had been applied by hand and then clamped with similar grafts to which tension had been applied with weights and then clamped. The grafts for the two experiments were obtained from thirty-four paired and ten unpaired knees. We also studied the effects of cooling on the biomechanical properties of grafts by comparing patellar ligament grafts tested at 13 degrees Celsius with those tested at room temperature. RESULTS: Two equally tensioned gracilis strands had 185 percent of the strength and 210 percent of the stiffness (1550+/-428 newtons and 336+/-141 newtons per millimeter, respectively) of one gracilis strand (837+/- 138 newtons and 160+/-44 newtons per millimeter, respectively). Two equally tensioned semitendinosus strands had 220 percent of the strength and 220 percent of the stiffness (2330+/-452 newtons and 469+/-185 newtons per millimeter, respectively) of one semitendinosus strand (1060+/-227 newtons and 213+/-44 newtons per millimeter, respectively). Four combined strands (two gracilis strands and two semitendinosus strands) that were equally tensioned with weights and clamped had the additive tensile properties of the individual strands. With the numbers available, four combined strands that were manually tensioned and clamped were not found to be significantly stronger or stiffer than two semitendinosus strands that were equally tensioned with weights (p>0.07). CONCLUSIONS: Four combined strands that were equally tensioned with weights and clamped were stronger and stiffer than all ten-millimeter patellar ligament grafts that have been described in previous reports. All strands of a hamstring graft must be equally tensioned for the composite to have its optimum biomechanical properties. CLINICAL RELEVANCE: Because of the well recognized donor-site morbidity associated with the use of patellar ligament grafts for reconstruction of the anterior cruciate ligament, multiple-strand hamstring-tendon grafts have become an increasingly popular choice. Our data demonstrate that equally tensioned four-strand hamstring-tendon grafts have initial tensile properties that are higher than those reported for ten-millimeter patellar-ligament grafts; thus, from a biomechanical point of view, they seem to be a reasonable alternative.

Aged↗

kappa-opioid regulation of neuronal activity in the rat supraoptic nucleus in vivo.

We investigated the influence of endogenous kappa-opioids on the activity of supraoptic neurons in vivo. Administration of the kappa-antagonist nor-binaltorphimine (200 micrograms/kg, i.v.), increased the activity of phasic (vasopressin), but not continuously active (oxytocin), supraoptic neurons by increasing burst duration (by 69 +/- 24%) and decreasing the interburst interval (by 19 +/- 11%). Similarly, retrodialysis of nor-binaltorphimine onto the supraoptic nucleus increased the burst duration (119 +/- 57% increase) of vasopressin cells but did not alter the firing rate of oxytocin cells (4 +/- 8% decrease). Thus, an endogenous kappa-agonist modulates vasopressin cell activity by an action within the supraoptic nucleus. To eliminate kappa-agonist actions within the supraoptic nucleus, we infused the kappa-agonist U50,488H (2.5 micrograms/hr at 0.5 micrograms/hr) into one supraoptic nucleus over 5 d to locally downregulate kappa-receptor function. Such infusions reduced the spontaneous activity of vasopressin but not oxytocin cells and reduced the proportion of cells displaying spontaneous phasic activity from 26% in vehicle-infused nuclei to 3% in U50, 488H-infused nuclei; this treatment also prevented acute inhibition of both vasopressin and oxytocin cells by U50,488H (1000 micrograms/kg, i.v.), confirming functional kappa-receptor downregulation. In U50, 488H-infused supraoptic nuclei, vasopressin cell firing rate was increased by nor-binaltorphimine (100 and 200 micrograms/kg, i.v.) but not to beyond that found in vehicle-treated nuclei, indicating that these cells were not U50,488H-dependent. Thus, normally functioning kappa-opioid mechanisms on vasopressin cells are essential for the expression of phasic firing.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Interruption of central noradrenergic pathways and morphine withdrawal excitation of oxytocin neurones in the rat.

1. We have tested the hypothesis that morphine withdrawal excitation of oxytocin neurones that follows from administration of naloxone to morphine-dependent rats is a consequence of excitation of noradrenergic neurones. 2. Female rats were made morphine dependent by intracerebroventricular (i.c.v.) infusion of the opioid at increasing doses over 5 days. On the sixth day, the rats were anaesthetized with urethane or pentobarbitone and prepared for blood sampling to determine plasma oxytocin by radioimmunoassay or for in vivo extracellular recording of the firing rate of identified oxytocin neurones from the supraoptic nucleus. Morphine withdrawal was induced by intravenous (i.v.) injection of the opioid antagonist naloxone (5 mg kg-1). 3. In one group of rats the noradrenergic projections to the hypothalamus were lesioned by i.c.v. injection of 6-hydroxydopamine immediately prior to the induction of morphine dependence. In these rats the oxytocin secretion induced by i.v. cholecystokinin was reduced to 9 % of that seen in sham-lesioned rats but in contrast, no attenuation of morphine withdrawal-induced oxytocin secretion was observed. 4. i.c.v. infusion of the alpha1-adrenoreceptor antagonist benoxathian, at up to 5.3 microg min-1, dose- dependently inhibited the withdrawal excitation of oxytocin neurones in morphine-dependent rats under urethane anaesthesia, and benoxathian reduced withdrawal-induced oxytocin secretion to 37 % of that of vehicle-infused rats. i.c.v. benoxathian also inhibited the activity of oxytocin neurones in morphine-naïve rats. Similarly, microdialysis administration of 2 mM benoxathian directly onto the surface of the supraoptic nucleus reduced the activity of oxytocin neurones by 53 %. 5. Thus noradrenergic systems are not essential for the expression of morphine withdrawal excitation, since chronic neurotoxic destruction of the noradrenergic inputs to the hypothalamus did not affect the magnitude of withdrawal-induced oxytocin secretion. However, tonically active noradrenergic inputs influence the excitability of oxytocin neurones, and acute antagonism of this noradrenergic tone can powerfully impair the ability of oxytocin neurones to exhibit morphine withdrawal excitation.

Adrenergic alpha-Antagonists↗

The effect of the level of aggression in the first grade classroom on the course and malleability of aggressive behavior into middle school.

This paper is on the influences of the classroom context on the course and malleability of aggressive behavior from entrance into first grade through the transition into middle school. Nineteen public elementary schools participated in developmental epidemiologically based preventive trials in first and second grades, one of which was directed at reducing aggressive, disruptive behavior. At the start of first grade, schools and teachers were randomly assigned to intervention or control conditions. Children within each school were assigned sequentially to classrooms from alphabetized lists, followed by checking to insure balanced assignment based on kindergarten behavior. Despite these procedures, by the end of first quarter, classrooms within schools differed markedly in levels of aggressive behavior. Children were followed through sixth grade, where their aggressive behavior was rated by middle school teachers. Strong interactive effects were found on the risk of being highly aggressive in middle school between the level of aggressive behavior in the first grade classrooms and each boy's own level of aggressive, disruptive behavior in first grade. The more aggressive first grade boys who were in higher aggressive first grade classrooms were at markedly increased risk, compared both to the median first grade boys, and compared to aggressive males in lower aggressive first grade classrooms. Boys were already behaving more aggressively than girls in first grade; and no similar classroom aggression effect was found among girls, although girls' own aggressive behavior did place them at increased risk. The preventive intervention effect, already reported elsewhere to reduce aggressive behavior among the more aggressive males, appeared to do so by reducing high levels of classroom aggression. First grade males' own poverty level was associated with higher risk of being more aggressive, disruptive in first grade, and thereby increased their vulnerability to classroom level of aggression. Both boys and girls in schools in poor communities were at increased risk of being highly aggressive in middle school regardless of their levels of aggressive behavior in first grade. These results are discussed in terms of life course/social field theory as applied to the role of contextual influences on the development and etiology of severe aggressive behavior.

Adolescent↗

Effects of syllable duration on stop-glide identification in syllable-initial and syllable-final position by humans and monkeys.

Humans and monkeys were compared in their identification of phoneme boundaries along synthetic stop-glide continua in syllable-initial /bo/-/wa/ or syllable-final /bab/-/baw/ contrasts differing in overall syllable duration. For both contrasts, humans were first tested with a conventional written identification procedure. Here, similar phoneme boundaries emerged and shifted with increases in syllable duration toward longer transitions, as has previously been reported in the literature for syllable-initial data (Miller & Liberman, 1979). Humans and monkeys were then tested on these contrasts, using a go/no-go identification procedure specifically designed for monkeys. Here also, stop-glide boundaries emerged and shifted with increased syllable duration for both species, although monkey "boundaries" were at longer durations than humans' in syllable-final position. The results indicate that there are both gross similarities and subtle differences between humans and monkeys with regard to the stop-glide context effect. The results are discussed in relation to the hypothesis that general mammalian auditory mechanisms are responsible for this effect.

Animals↗

Local opioid inhibition and morphine dependence of supraoptic nucleus oxytocin neurones in the rat in vivo.

1. Single neurones of the rat supraoptic nucleus were recorded during microdialysis of naloxone onto the ventral surface of the nucleus in anaesthetized rats. We used this combination of techniques to test whether the acute or chronic effects of systemically or centrally applied opioids upon oxytocin cell activity were due to actions of the opioids within the nucleus itself. 2. Supraoptic nucleus oxytocin neurones were identified antidromically and by an excitatory response to intravenously injected cholecystokinin. Acute intravenous injection of the kappa-agonist U50488H or the mu-agonist morphine (1-5 mg kg-1) reduced the firing rate of identified oxytocin neurones by 97.7 +/- 4.8% (n = 6) and 94.1 +/- 4.1% (n = 7), respectively. The inhibition by each of these opioids was completely reversed after administration by microdialysis (retrodialysis) of the opioid antagonist naloxone (0.1-1.0 microgram microliter-1 at 2 microliters min-1) onto the exposed ventral surface of the supraoptic nucleus. 3. Retrodialysis of naloxone (0.1-10.0 micrograms microliter-1) onto the supraoptic nucleus of rats made dependent by intracerebroventricular morphine infusion for 5 days increased the firing rate of oxytocin neurones from 0.9 +/- 0.4 to 3.1 +/- 0.7 spikes s-1 (P < 0.05, n = 6). This increase in firing rate from basal was 58.5 +/- 15.1% of that following subsequent intravenously injected naloxone (5 mg kg-1). 4. Thus, the acute inhibition of supraoptic nucleus oxytocin neurones which results from systemic administration of opioid agonists primarily occurs within the supraoptic nucleus itself, since the antagonist naloxone was effective when given into the supraoptic nucleus. Furthermore, oxytocin neurones develop morphine dependence by a mechanism which is distinct from an action on their distant afferent inputs. Nevertheless, withdrawal excitation of these afferent inputs may enhance the magnitude of oxytocin neurone withdrawal excitation.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

Oxytocin neurone autoexcitation during morphine withdrawal in anaesthetized rats.

We investigated whether release of oxytocin into the supraoptic nucleus is involved in morphine-withdrawal excitation of oxytocin neurones. Retrodialysis of naloxone into the supraoptic nucleus of morphine-dependent rats increased intranuclear oxytocin release by 56.5p +/- 12.7% whereas no change was seen in vehicle-treated dependent rats. In another experiment, in morphine-dependent rats given intravenous (i.v.) naloxone, intracerebroventricular (i.c.v.) oxytocin receptor antagonist injection reduced the increase of plasma oxytocin concentration (to 28-fold) compared with i.c.v. vehicle (62-fold increase). Finally, the increase in oxytocin neurone firing rate following morphine-withdrawal in the presence of i.c.v. oxytocin antagonist infusion was 28% of the steady state firing rate (15-20 min later) and this was lower (p < 0.05) than the percentage increase in i.c.v. vehicle-infused rats (89%). Thus, central endogenous oxytocin may be involved in withdrawal excitation of oxytocin neurones.

Action Potentials↗