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Biomedical subjects

P C Nolan

Publications and source records attributed to P C Nolan.

At least 19 recordsLinked to original sources

Enhancement of human osteoblast proliferation and phenotypic expression when cultured in human serum.

Traditionally, culture medium is supplemented with foetal bovine serum (FBS). However, in cultures of osteoblasts intended for human re-implantation, such serum presents potential risks of foreign protein contamination and transmission of viral or prion-related material, if used. We cultured human osteoblasts from 16 patients in 10% autologous human serum, 10% pooled human serum, 10% FBS or 2% Ultroser G. Non-synthetic sera were tested in both heat-treated and non-heat-treated forms. We determined cell growth and osteoblast phenotype. Cell proliferation in all types of human serum was significantly greater than in FBS. This was most marked in heat-treated autologous human serum. Cells cultured in Ultroser G had less proliferation than all other groups. The phenotypic tests showed that cells cultured in human and foetal bovine serum displayed an osteoblast phenotype, with greater protein expression in cells cultured in human serum. We conclude that culture of human osteoblasts in autologous human serum enhances cell proliferation, while maintaining an osteoblast phenotype. These findings have implications for the use of cultured osteoblasts in self-cell therapy. Human osteoblast growth is supported by autologous human serum, which allows re-implantation of cultured cells, while avoiding the risk of foreign protein carry-over with enhancement of cell proliferation.

Aged↗

Evaluation of electromyographic monitoring during insertion of thoracic pedicle screws.

We prospectively studied the use of intercostal EMG monitoring as an indicator of the accuracy of the placement of pedicle screws in the thoracic spine. We investigated 95 thoracic pedicles in 17 patients. Before insertion of the screw, the surgeon recorded his assessment of the integrity of the pedicle track. We then stimulated the track using a K-wire pedicle probe connected to a constant current stimulator. A compound muscle action potential (CMAP) was recorded from the appropriate intercostal or abdominal muscles. Postoperative CT was performed to establish the position of the screw. The stimulus intensity required to evoke a muscle response was correlated with the position of the screw on the CT scan. There were eight unrecognised breaches of the pedicle. Using 7.0 mA as a threshold, the sensitivity of EMG was 0.50 in detecting a breached pedicle and the specificity was 0.83. Thoracic pedicle screws were accurately placed in more than 90% of patients. EMG monitoring did not significantly improve the reliability of placement of the screw.

Adult↗

Transverse sacral fractures: case series and literature review.

OBJECTIVES: To report experience with transverse sacral fracture, an uncommon injury frequently associated with neurologic deficit, and to perform a meta-analysis of the literature in order to define the role of decompression for the management of sacral fractures. DESIGN: A review of 7 cases. SETTING: A university-affiliated tertiary care centre. PATIENTS: Seven patients with transverse fractures of the sacrum. The mean follow-up was 13 months. INTERVENTIONS: A review of the clinical data and a search of the literature for studies that reported on 4 or more patients with a transverse sacral fracture. MAIN OUTCOME MEASURES: Mechanism of injury, type of neurologic deficit and its management. RESULTS: The most common mechanism in the 7 study patients was a fall from a height. Six patients had neurologic deficits, mostly in the form of bowel or bladder disturbance. Five of these were treated with surgical decompression, and 4 of them had an improvement in neurologic function. The 7 original studies from the literature dealt with a total of 55 patients. As in the study patients, falls from a height and motor vehicle accidents predominated as the mechanisms of injury. In contrast to patients in this study, 20 of 48 patients in the literature review with neurologic deficits were treated conservatively. CONCLUSIONS: The outcomes in this study are similar to those reported in the literature. The place of surgical decompression for patients with neurologic deficit cannot be clearly determined from the evidence currently available.

Accidental Falls↗

Dia-metaphyseal distal tibial fractures--treatment with a shortened intramedullary nail: a review of 15 cases.

Fifteen patients were reviewed retrospectively with distal tibial fractures treated with a reamed intramedullary nail which had approximately 1 cm removed just distal to the lowermost locking screw. There were 15 patients (nine males and six females). All patients had returned to normal activities of daily living. Eleven patients could perform all leisure activities with no symptoms and three had only minor discomfort, which did not preclude sport. All fractures united, 12 uneventfully and three after a secondary surgical procedure. Three patients had malalignment defined as varus-valgus angulation or recurvatum of 5 degrees or greater. Whilst technically challenging, intramedullary nailing for dia-metaphyseal distal tibial fractures represents a safe and reliable method for managing these injuries. This represents the first report in the English Language literature specifically examining treatment with a shortened tibial nail.

Adult↗

The price of peace: the personal and financial cost of paramilitary punishments in Northern Ireland.

The aim of this study was to compare the injuries sustained during paramilitary punishments both before and after the onset of "peace" in Northern Ireland. A retrospective chart review was performed looking at age, injuries, treatments instituted, theatre time, length of hospital stay and overall cost of care. In the 10-month period before the ceasefire, 31 patients were treated after sustaining paramilitary punishment shootings. Mean age was 25.2 years. All patients had small entrance and exit wounds with minimal soft tissue disruption. A total of 18 fractures were recorded in 15 patients and 14 arteries required repair. Mean operative time was 2.6 h, mean hospital stay 7.61 days and mean cost per patient 3102 Pounds. In the following 10-month period 28 patients were admitted after punishments, only one of whom had been shot, all others had been beaten with sticks and clubs. Mean age was 27.4 years. In 52 limbs, 64 fractures were recorded and 44% of these were open; 15 of the fractures were Gustilo and Anderson Grade III or greater and 11 of the fractures were intra-articular. There were no arterial injuries. Mean operative time was 2.6 h, mean hospital stay 12.4 h and mean cost per patient 3849 Pounds.

Cost of Illness↗

In vitro responses of neurons in the periaqueductal gray to hypoxia and hypercapnia.

Hypoxia-sensitive neurons in the caudal hypothalamus (CH) have been shown to project to the periaqueductal gray (PAG) which, in turn, sends descending projections to an area of the ventrolateral medulla (VLM) containing neurons inherently excited by hypoxia. The purpose of this study was to determine if neurons in the PAG are excited by hypoxia or hypercapnia in an in vitro environment. Extracellular responses to hypoxia and hypercapnia of neurons located throughout the PAG were recorded in a rat brain slice (400-500 microm thick) preparation. Hypoxic (10% O(2)/5% CO(2)/85% N(2)) and hypercapnic (7% CO(2)/93% O(2)) stimuli were delivered to the tissue through gas bubbled into the brain slice chamber. A majority (39 of 53) of the neurons tested responded to hypoxia. Of these neurons, 92% responded to hypoxia with an increase in firing rate. Neurons in the dorsolateral/lateral regions increased firing rates to a greater extent than neurons located in ventrolateral regions. All neurons tested (n=6) also responded to hypoxia after perfusion of the tissue with a low Ca(2+)/high Mg(2+) solution to block classic synaptic transmission. Only a small proportion (7/33) of neurons tested responded to hypercapnia. These findings indicate that neurons in the periaqueductal gray region of the brain have an inherent responsiveness to hypoxia and, thus, may contribute to the overall coordination of cardiorespiratory responses to systemic hypoxia.

Animals↗

Ventrolateral medullary neurons show age-dependent depolarizations to hypoxia in vitro.

Central mechanisms are likely responsible for the larger respiratory activation in response to hypoxia in the adult compared to the neonatal animal. One possible site for this effect is in the ventrolateral medulla, an area known to be involved in the cardiorespiratory responses to hypoxia. Neurons in this area are stimulated by hypoxia both in vivo and in vitro. The purpose of the present study was to determine if changes in the magnitude of this excitatory response occur during early postnatal development. Whole-cell patch recordings were made from neurons in the ventrolateral medulla (VLM) in a 400-micrograms brain slice preparation. The basal properties and responses to a brief (90 s) hypoxic stimulus (5% CO2/95% N2) were compared between neurons from neonatal (P < 16) and juvenile (P16-38) rats. An excitation consisting of a depolarization, increase in spike frequency and decrease in input resistance was observed during hypoxia in eighty-three percent of juvenile but in only 58% of the neonatal VLM neurons. Moreover, the magnitude of this response was greater in the juvenile (8.2 +/- 1.3 mV) than in the neonatal (4.8 +/- 0.5 mV) neurons. A second type of depolarizing response, consisting of a more pronounced depolarization interrupted by a brief hyperpolarization that returned to a depolarized state and not associated with an increased discharge frequency, occurred in only 3% of the neurons from the juvenile animals compared to 18% of those from neonatal rats. The remaining proportion of the VLM neurons studied were hyperpolarized or were unaffected by hypoxia. Measurements of tissue pO2 indicate that none of the above differences are due to variations in the hypoxic stimulus between neonatal and adult slices. The results of this study suggest that the hypoxic-induced depolarizations observed in VLM neurons change during development. These developmental changes may contribute to the changes that occur in cardiorespiratory responses to acute systemic hypoxia during early development.

Aging↗

The changing pattern of paramilitary punishments in Northern Ireland.

Paramilitary punishments in Northern Ireland traditionally involved shooting in the limbs with low-velocity handguns. During the recent IRA ceasefire they were replaced with beatings by clubs and similar objects. We carried out a retrospective review of patients who had suffered punishment beatings who presented to the Royal Victoria Hospital, Belfast. Patients were more likely to have fractures and more severe soft-tissue injuries. The time spent in hospital was often longer, and there was a greater chance of requiring operations (often multiple).

Fractures, Bone↗

In vitro responses of VLM neurons to hypoxia after normobaric hypoxic acclimatization.

Hypoxic acclimatization involves an initial rapid ventilatory response followed by a more gradual increase in ventilation over a period of 24 to 48 h in both humans and rats. In addition, the acute ventilatory response to hypoxia is accentuated following hypoxic acclimatization. The purpose of the present investigation was to determine if hypoxic acclimatization augments the acute hypoxic response of neurons in the ventrolateral medulla (VLM). Brain slices (400 microns) containing the ventrolateral medulla were prepared from Sprague-Dawley rats acclimatized to hypoxia (10% O2) for 4-5 days (n = 4) and 9-10 days (n = 4) and from rats maintained in a normoxic environment (n = 4). Extracellular recordings demonstrated that there were no significant differences in the basal pattern or discharge rate of VLM neurons from animals exposed to short (10.8 +/- 0.9 Hz, n = 51), or long (10.1 +/- 1.1 Hz, n = 59) periods of hypoxia compared to control neurons (10.8 +/- 1.1 Hz, n = 52). The proportion of neurons stimulated (approximately 70%), inhibited (approximately 20%) and unaffected (approximately 10%) by an acute bout of hypoxia (10% O2) was also similar among groups. However, acute hypoxia elicited a greater increase in discharge frequency in neurons from rats exposed to the short period of hypoxia compared to the responses from neurons in the control and longer acclimatization groups. Thus, the responsivity of VLM neurons during the early stages of hypoxic acclimatization is altered in a manner consistent with the respiratory responses associated with acclimatization.

Acclimatization↗

Biocompatibility of xenogeneic bone, commercially available coral, a bioceramic and tissue sealant for human osteoblasts.

The drawbacks of freshly harvested autologous bone have resulted in the search for an alternative, capable of supporting osteogenic cell growth. This capability was examined in potential bone graft materials by culturing human osteoblasts on each material. Test materials included rat bone, Surgibone, Ostilit, Biocoral and Tisseel. After 3 days osteoblasts had adhered to all materials, except Ostilit. With increasing time the cells multiplied on the materials, to varying extents. Cell affinity was greatest for rat bone and Tisseel. Fewer cells attached to Biocoral and Surgibone. Thus all the materials, with the exception of Ostilit, were biocompatible for human osteoblasts.

Animals↗

In vivo and in vitro responses of neurons in the ventrolateral medulla to hypoxia.

Neurons in the ventrolateral medulla (VLM) are known to be involved in several cardiorespiratory reflexes and to provide tonic drive to sympathetic preganglionic neurons. Recent studies have suggested that VLM neurons modulate the respiratory responses to hypoxia and to hypercapnia. The purpose of the present study was to determine with electrophysiological techniques if the discharge of these neurons is altered by hypoxia and/or by hypercapnia both in vivo and in vitro. Extracellular single-unit activity of VLM neurons (n = 39) was recorded during inhalation of a hypoxic gas (10% O2) and during inhalation of a hypercapnic gas (5% CO2) in anesthetized, spontaneously breathing rats (n = 16). Hypoxia elicited an increase in the discharge frequency in 64% of the VLM neurons studied; hypercapnia stimulated 42% of the neurons. Fifty-two percent of the neurons were stimulated by both hypoxia and hypercapnia. Signal averaging revealed that 76% of the hypoxia-stimulated neurons had a resting discharge related to the cardiac and/or respiratory cycle. Similar percentages of VLM neurons (35/54) were stimulated by hypoxia in a second group of animals (n = 14) that were studied after sinoaortic denervation. A rat brain slice preparation was then used to determine if hypoxia exerts a direct effect upon neurons in the VLM. Perfusing a hypoxic gas over the surface of medullary slices evoked an increase in the discharge frequency in the majority (39/49) of VLM neurons studied; responses were graded in relation to the magnitude of the hypoxic stimulus. Similar responses to hypoxia were observed in VLM neurons studied during perfusion with a synaptic blockade medium. Retrograde labeling of VLM neurons with rhodamine tagged microspheres injected into the thoracic intermediolateral cell column demonstrated that the hypoxia sensitive neurons were located in a region of the VLM that projects to the thoracic spinal cord. These results demonstrate that neurons in the ventrolateral medulla are excited by a direct effect of hypoxia; these neurons may play a critical role in the cardiorespiratory responses to hypoxia.

Animals↗

An excitatory amino acid synapse in the thoracic spinal cord is involved in the pressor response to muscular contraction.

The increase in arterial pressure and heart rate elicited during exercise are produced by descending central command and by feedback from contracting limb muscles. Previous studies from this laboratory have demonstrated that neurons in the ventrolateral medulla (VLM) that project to the intermediolateral (IML) columns of the thoracic spinal cord are involved in the mediation of the pressor response to contraction of hind limb muscles. This study determines if these VLM neurons utilize excitatory amino acids (EAA) as the neurotransmitter at the synapse on IML neurons. The arterial pressure and heart rate responses to static muscular contraction, elicited by stimulation of the L7 and S1 ventral roots, and to electrical stimulation in the caudal hypothalamus were examined in anesthetized cats. Both muscular contraction and hypothalamic stimulation elicited significant increases in arterial pressure and heart rate. Intrathecal administration of the broad spectrum, postsynaptic EAA antagonist, kynurenic acid, greatly reduced (-77%) the pressor response to muscular contraction. A smaller (-27%) decrease in the magnitude of pressor response elicited by muscular contraction was produced by intrathecal administration of 2-amino-4-phosphonobutyric acid which acts on a presynaptic EAA receptor. Neither antagonist affected the heart rate responses associated with muscular contraction or the cardiovascular responses to hypothalamic stimulation. These results indicate that the pressor response elicited by feedback from contracting hind limb muscles is mediated through an excitatory amino acid synapse in the spinal cord.

Amino Acids↗

Living bone grafts.

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Bone Transplantation↗