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Biomedical subjects

N R Jones

Publications and source records attributed to N R Jones.

At least 19 recordsLinked to original sources
PubMed2006

Patterns of global tobacco use in young people and implications for future chronic disease burden in adults.

BACKGROUND: Tobacco use is a leading preventable risk factor for many chronic disorders, which are expected to account for an increasing share of the global disease burden. As part of the Global Youth Tobacco Survey (GYTS), we aimed to assess the effect of tobacco use by young people on global mortality. METHODS: GYTS is a school-based survey of students aged 13-15 years. The survey was undertaken at 395 sites in 131 countries and the Gaza Strip and West Bank. We questioned students about current tobacco use, susceptibility to smoking among non-smokers, and exposure to secondhand smoke at home and in public places. FINDINGS: The difference in current cigarette smoking between boys and girls is narrower than expected in many regions of the world. Use of tobacco products other than cigarettes by students is as high as cigarette smoking in many regions. Almost one in five never-smokers reported they were susceptible to smoking in the next year. Student exposure to secondhand smoke was high both at home (more than four in ten) and in public places (more than five in ten). Never-smokers were significantly less likely than current smokers to be exposed to secondhand smoke at home (prevalence 39.1% [95% CI 36.6-41.6] vs 72.8% [64.0-81.6]) and in public places (49.5% [46.7-52.3] vs 81.2% [74.2-88.2]). INTERPRETATION: Our findings are troubling for the future of chronic disease and tobacco-related mortality. Reduction of tobacco consumption will require a redoubling of efforts to prevent initiation and promote cessation among the large proportion of young people who currently use tobacco. High exposure to secondhand smoke suggests a need for countries to pass strong and effective smoke-free policies.

Adolescent↗
PubMed2004

Neuropsychological and information processing performance and its relationship to white matter changes following moderate and severe traumatic brain injury: a preliminary study.

Reductions in information processing speed have frequently been reported following moderate and severe traumatic brain injuries (TBIs), consistent with the effects of diffuse white matter damage. Although the corpus callosum (CC) is a common site for diffuse damage following TBI, the effects of this damage on information processing speed have not been adequately examined. This study assessed a TBI group and a matched control group on tests of attention, memory, fluency, and set shifting ability, together with reaction time (RT) tasks requiring the inter- and intrahemispheric processing of visual and tactile information. The RT tasks were designed to target the cognitive functions that are likely to be affected by diffuse white matter damage, including damage to the CC. The TBI group demonstrated deficits in verbal and visual fluency and verbal memory. They were also slower on the visual and tactile RT tasks, were more affected by task complexity, and slower on RT tasks requiring the interhemispheric transfer of information. In fact, one of the interhemispheric tactile RT tasks proved to be the most discriminating of all the cognitive and RT measures. MRIs completed on a subset of TBI participants indicated that the mean CC measurements were 5% to 19% smaller than a normative control group, with the most atrophied areas being the isthmus and anterior midbody. Although white matter atrophy was moderately related to visual and tactile RT performance, and total hippocampal volume related to memory performance, CC area was not related to many of the tasks that were designed to tap interhemispheric processing. None of the standard cognitive tests correlated with outcome in the TBI group, but 1 of the tactile RT measures was significantly related to 2 measures of outcome.

Adolescent↗
PubMed2001

Excitotoxic model of post-traumatic syringomyelia in the rat.

STUDY DESIGN: A rat model was developed to elucidate the role of excitatory amino acids and spinal subarachnoid block in the genesis of post-traumatic syringomyelia. This excitotoxic model produces intramedullary cavities rather than the dilation of the central canal (canalicular syringomyelia) created by previous animal models. OBJECTIVES: To produce extracanalicular cysts in the rat spinal cord with quisqualic acid, a potent agonist of multiple excitatory amino acid receptors, and to compare the effects of excitotoxic injury only with that of excitotoxic injury and subarachnoid block with kaolin. SUMMARY OF BACKGROUND DATA: In post-traumatic syringomyelia, primary injury and excitotoxic cell death secondary to elevated levels of excitatory amino acids may initiate a pathologic process leading to the formation of spinal cavities. Subarachnoid block by arachnoiditis may promote enlargement of the cavities. METHODS: Three control rats received a unilateral injection of normal saline into the spinal cord, and another five rats received an injection of kaolin into the spinal subarachnoid space. Quisqualic acid was injected unilaterally into the spinal cord of 20 rats, and 13 additional rats received a unilateral injection of quisqualic acid into the spinal cord after injection of kaolin into the subarachnoid space. Histologic and immunocytochemical assessments were undertaken. RESULTS: In the control groups, no parenchymal cyst developed in any of the animals. Spinal cord cyst formation was observed in 16 of 19 animals in the quisqualic acid groups, but no cysts exceeding two segments in the length of the spinal cord developed in any of the rats. Much larger cavities were seen in 9 of 11 animals in the group with quisqualic acid and kaolin, and cysts exceeding two segments developed in all 9 of these (9/11; 82%). CONCLUSIONS: In post-traumatic syringomyelia, excitotoxic cell death occurring secondarily to elevated levels of excitatory amino acids may contribute to the pathologic process leading to the formation of spinal cord cysts. Subarachnoid block by arachnoiditis is likely to cause enlargement of the cavity.

Animals↗
PubMed2000

Topography and severity of axonal injury in human spinal cord trauma using amyloid precursor protein as a marker of axonal injury.

STUDY DESIGN: Axonal injury was examined in 18 human cases of acute spinal cord compression using amyloid precursor protein as a marker of AI. OBJECTIVES: To topographically map and semiquantitate axonal injury in spinal cord compression of sufficient severity to produce para- or quadriplegia. SUMMARY OF BACKGROUND DATA: Amyloid precursor protein is carried along the axon by fast axoplasmic transport and has been extensively used as a marker of traumatic axonal injury. METHODS: The study group comprised 18 cases of spinal cord compression (17 due to fracture dislocation of the vertebral column and 1 iatrogenic compression from Harrington rods) and two normal control. All the cords were examined according to a standard protocol, and at least 10 segmental levels were immunostained using a monoclonal antibody to amyloid precursor protein and immunopositive AI was semiquantitated using a grading system to provide the axonal injury severity score (AISS). The focal injury at the site of cord compression (haemorrhage, haemorrhagic necrosis, ischaemic necrosis) was also semiquantitated to provide the focal injury area score (FIAS). AI occurring around the site of focal compression (focal axonal injury severity score or FAISS) was distinguished from AI distant to the focal injury (nonfocal axonal injury severity score or NFAISS). RESULTS: All 18 cases showed widespread amyloid precursor protein immunoreactive axonal injury and the AISS ranged from 28 to 60%. In all cases, the FAISS was greater than the NFAISS and there was a statistically significant relationship between the AISS and the FIAS. CONCLUSION: Acute spinal cord compression of sufficient severity to produce permanent paralysis causes widespread axonal damage that is maximal at the site of compression but also present throughout the length of the cord in segments far distant from the site of the focal injury.

Adolescent↗
PubMed2000

Cervical and thoracic juxtafacet cysts causing neurologic deficits.

STUDY DESIGN: Case reports and review of the literature. OBJECTIVES: To review the clinical features, treatment, and outcome of juxtafacet cysts. SUMMARY OF BACKGROUND DATA: There have previously been 4 reported cases of thoracic juxtafacet cysts and 19 cases of cervical juxtafacet cysts. Cervical cysts have usually originated from the cruciate ligament and caused myelopathy. Thoracic cysts are usually signaled by myelopathy. METHODS: The records of the Neurosurgery Department of Royal Adelaide Hospital from 1980 through 1995 were reviewed for cases of intraspinal juxtafacet cysts. RESULTS: Eight cases of intraspinal juxtafacet cysts were identified; six were in the lumbar spine. One patient had a cervical cyst related to a facet joint and had unilateral radiculopathy. A second patient with a thoracic cyst had the gradual onset of myelopathy. Both patients had surgical excision of the cyst without resection of the adherent dura. The symptoms and neurologic signs improved in each case. CONCLUSIONS: Cervical and thoracic juxtafacet cysts are rare lesions that are usually signaled by myelopathy. Results of surgery are excellent in most cases, even if the cyst is not completely excised.

Aged↗
PubMed2000

Mechanisms underlying the formation and enlargement of noncommunicating syringomyelia: experimental studies.

The pathogenesis of noncommunicating syringomyelia is unknown, and none of the existing theories adequately explains the production of cysts that occur in association with conditions other than Chiari malformation. The authors' hypothesis is that an arterial pulsation-driven perivascular flow of cerebrospinal fluid (CSF) is responsible for syrinx formation and enlargement. They investigated normal CSF flow patterns in 20 rats and five sheep by using the tracer horseradish peroxidase; the effect of reducing arterial pulse pressure was examined in four sheep by partially ligating the brachiocephalic trunk; CSF flow was examined in 78 rats with the intraparenchymal kaolin model of noncommunicating syringomyelia; and extracanalicular cysts were examined using the excitotoxic model in 38 rats. In the normal animals there was a rapid flow of CSF from the spinal subarachnoid space into the spinal cord perivascular spaces and then into the central canal. This flow ceased when arterial pulsations were diminished. In animals with noncommunicating syringomyelia, there was rapid CSF flow into isolated and enlarged segments of central canal, even when these cysts were causing pressure damage to the surrounding spinal cord. Exitotoxic injury of the spinal cord caused the formation of extracanalicular cysts, and larger cysts were produced when this injury was combined with arachnoiditis, which impaired subarachnoid CSF flow. The results of these experiments support the hypothesis that arterial pulsation-driven perivascular fluid flow is responsible for syrinx formation and enlargement.

Animals↗
PubMed2000

Upregulation of neuronal amyloid precursor protein (APP) and APP mRNA following magnesium sulphate (MgSO4) therapy in traumatic brain injury.

The aim of this study was to assess and quantitate topographically the effects of posttraumatic intravenous magnesium sulphate (MgSO4) on neuronal perikaryal APP antigen and messenger RNA (mRNA) expression in sheep brains 2 h after a controlled focal head impact. The percentage brain area with APP immunoreactive neuronal perikarya was 71, 56, 27.5 and 5.5%, respectively, in MgSO4-treated head-injured animals, head-injured animals without any treatment, MgSO4 treated nonimpacted animals, and nontreated nonimpacted control sheep. Although there was no statistically significant difference in APP immunoreactive neuronal perikarya in the MgSO4-treated HI group (mean 71%) compared to the HI group without any treatment (mean 56%), northern analysis showed that there was a 2.3-+/-0.2-fold increase in APP mRNA in the thalamus of treated impacted animals compared to untreated impacted animals (p < 0.005). However, MgSO4 treated nonimpacted control animals also showed a 1.6-+/-0.1-fold increase in APP mRNA compared to untreated nonimpacted controls (p < 0.005). MgSO4 therapy results in upregulation of neuronal APP mRNA and APP expression that is quantitatively greater following a focal head impact.

Amyloid beta-Protein Precursor↗
PubMed1999

Upregulation of amyloid precursor protein messenger RNA in response to traumatic brain injury: an ovine head impact model.

There is evidence that the amyloid precursor protein (APP) plays an important role in neuronal growth and synaptic plasticity and that its increased expression following traumatic brain injury represents an acute phase response to trauma. We hypothesized that the previously described increased APP expression in response to injury (Van den Heuvel et al., Acta Neurochir. Suppl. 71, 209-211) is due to increased mRNA expression and addressed this by examining the expression of APP mRNA and APP within neuronal cell bodies over time in an ovine head impact model. Twenty-five anesthetized and ventilated 2-year-old Merino ewes sustained a left temporal head impact using a humane stunner and 9 normal sheep were used as nonimpact controls. Following postimpact survival periods of 15, 30, 45, 60, and 120 min, brains were perfusion fixed in 4% paraformaldehyde and examined according to standard neuropathological protocol. APP mRNA and antigen expression were examined in 5-microm sections by nonisotopic in situ hybridization and APP immunocytochemistry. The percentage of brain area with APP immunoreactivity within neuronal cell bodies in the impacted animals increased with time from a mean of 7.5% at 15 min to 54.5% at 2 h. Control brains showed only very small numbers of weakly APP-positive neuronal cell bodies ranging from 2 to 14% (mean 7%). Increased expression of APP mRNA was first evident in impacted hemispheres at 30 min after impact and progressively increased over time to involve neurons in all sampled regions of the brain, suggesting increased transcription of APP. In contrast, APP mRNA was undetectable in tissue from nonimpacted sheep. These data show that APP mRNA and antigen expression are sensitive early indicators of neuronal injury with widespread upregulation occurring as early as 30 min after head impact.

Amyloid beta-Protein Precursor↗
PubMed1999

Cerebrospinal fluid flow in an animal model of noncommunicating syringomyelia.

OBJECTIVE: The source of fluid and the mechanism of cyst enlargement in syringomyelia are unknown. It has been demonstrated that cerebrospinal fluid (CSF) normally flows from the subarachnoid space through perivascular spaces and into the spinal cord central canal. The aim of this study was to investigate whether this flow continues during cyst formation in an animal model of syringomyelia and to determine the role of subarachnoid CSF flow in this model. METHODS: The intraparenchymal kaolin model of noncommunicating syringomyelia was established in 78 Sprague-Dawley rats. Horseradish peroxidase was used as a tracer to study CSF flow at 1 day, 3 days, 1 week, and 6 weeks after kaolin injection. CSF flow was studied at 0, 10, and 30 minutes after horseradish peroxidase injection into the cisterna magna or thoracic subarachnoid space. RESULTS: The central canal became occluded at the level of the kaolin injection and at one or more rostral levels. Segments of the central canal isolated between occlusions gradually dilated, and axonal retraction balls were detected in the surrounding white matter. There was a partial blockage of subarachnoid CSF flow at the site of the kaolin injection, both in a rostral-caudal direction and in a caudal-rostral direction. Horseradish peroxidase was detected at all time points, in a distinctive pattern, in perivascular spaces and the central canal. This pattern was seen even where segments of the central canal were isolated and dilated. CONCLUSION: In this animal model, noncommunicating syringes continue to enlarge even when there is evidence that they are under high pressure. There may be an increase in pulse pressure rostral to the block of subarachnoid CSF flow, causing an increase in perivascular flow and contributing to syrinx formation. The source of fluid in noncommunicating syringomyelia may be arterial pulsation-dependent CSF flow from perivascular spaces into the central canal.

Animals↗
PubMed1998

A technique for in vivo vascular perfusion fixation of the sheep central nervous system.

A method for perfusion fixation of the sheep central nervous system is described. The technique utilises the vascular anatomy of the spinal cord and brain to provide fixation that is comparable to transcardiac perfusion of the small animal. It can be applied with relative ease, cost effectiveness and without risking premature death of the animal due to complications of a major procedure such as thoracotomy.

Animals↗
PubMed1998

The central canal of the human spinal cord: a computerised 3-D study.

Knowledge of the structure and function of the central canal of the human spinal cord is important in understanding the pathogenesis of syringomyelia. Analysis of the morphology of the central canal is difficult using isolated histological sections. A 3-dimensional reconstruction technique using digitised histological sections was therefore developed to visualise the morphology of the central canal. The technique was used to study the canal in the conus medullaris and filum terminale of 1 sheep and 4 human spinal cords. A variety of morphological features were demonstrated including canal duplication, a terminal ventricle and openings from the canal lumen into the subarachnoid space. The findings suggest the possibility of a functionally important fluid communication in the caudal spinal cord which may have a sink function.

Adult↗
PubMed1997

Arterial pulsation-dependent perivascular cerebrospinal fluid flow into the central canal in the sheep spinal cord.

The impetus for the enlargement of syringes is unknown. The authors hypothesize that there is a flow of cerebrospinal fluid (CSF) from perivascular spaces into the central canal and that the flow is driven by arterial pulsations. Using horseradish peroxidase as a tracer, the CSF flow was studied in normal sheep, in sheep with damped arterial pulsations, and in sheep with lowered spinal subarachnoid pressure. The CSF flow from perivascular spaces into the central canal was demonstrated in the normal sheep, and two patterns of flow were identified: 1) from perivascular spaces in the central gray matter; and 2) from perivascular spaces in the ventral white commissure. Flow into the central canal was also observed in the sheep with lowered spinal subarachnoid pressure, but not in those with reduced arterial pulse pressure. This study provides evidence that CSF flow from perivascular spaces into the central canal is dependent on arterial pulsations. Arterial pulsation-driven CSF flow may be the impetus for the expansion of syringes.

Animals↗
PubMed1996

Evidence for rapid fluid flow from the subarachnoid space into the spinal cord central canal in the rat.

Horseradish peroxidase (HRP) was used as a CSF tracer in Sprague-Dawley rats. One group of rats received an injection of HRP in the cisterna magna and a second group was injected in the thoracic spinal subarachnoid space. The animals were sacrificed 0, 10 or 30 min after HRP injection by rapid perfusion with paraformaldehyde and glutaraldehyde. In both groups, there was rapid HRP labeling of brain and spinal cord perivascular spaces. HRP was present in the central canal in a pattern that was not consistent with flow from the fourth ventricle: in both groups there were segments of unlabeled central canal between the fourth ventricle and central canal segments containing HRP. HRP-labeled perivascular spaces were seen in the central gray matter adjacent to the central canal. There was a distinctive pattern of interstitial HRP between perivascular spaces and the central canal. The results suggest that there is a normal flow of fluid from the subarachnoid space, into the perivascular spaces, across the interstitial space and into the central canal. The function of this flow may be to clear metabolites from the interstitial space. The existence of such a flow would add considerable support to the theory that non-communicating syringomyelia develops in segments of central canal isolated by occlusion or stenosis at each end.

Animals↗
PubMed1996

Choroid plexus arteriovenous malformations. A report of four pathologically proven cases and review of the literature.

The clinical, radiological and pathological findings of four cases of primary intraventricular haemorrhage secondary to choroid plexus arteriovenous malformations (AVM) are described and the relevant literature reviewed. In three of the cases the diagnosis was confirmed or made at autopsy. The fourth case survived to undergo craniotomy followed by radiosurgery with excellent results. All AVMs originated in the choroid plexus of the lateral ventricle, and autopsy confirmation required a high degree of suspicion and the systematic microscopic examination of serial coronal sections of the ventricle with the clot in situ.

Adult↗
PubMed1996

A head impact model of early axonal injury in the sheep.

Axonal injury (AI), one of the principal determinants of clinical outcome after head injury, may evolve over several hours after injury, raising the future possibility of therapeutic intervention during this period. A new head impact model of AI in sheep was developed to examine pathological and physiological changes in the brain resulting from a graded traumatic insult. In this preliminary study 10 anesthetized and ventilated Merino ewes were used. Head injury was produced by impact from a humane stunner to the temporal region of an unrestrained head. Eight sheep were studied for 1, 2, 4, or 6 h after impact. Two sham animals (no impact, 6 h survival) were also examined. Arterial blood pressure, intracranial pressure, and cerebral blood flow were monitored continuously. A physiological index of injury severity was calculated by weighting the percentage shift from preinjury values for each monitored parameter over the first hour after injury. Immunostaining with amyloid precursor protein (APP) was used as a marker of axonal damage and the distribution of APP positive axons was recorded according to a sector scoring method (APPS). Widespread AI was identified in 7 of the 8 impacted animals, around cerebral contusions and in hemispheric white matter, central gray matter, brain stem, and cerebellum, and was detected as early as 1 h after injury. The degree of axonal injury (APPS) correlated well with an index of physiological response to injury (r = 0.83, p = 0.005).

Amyloid beta-Protein Precursor↗
PubMed1993

Extradural haematoma: trends in outcome over 35 years.

We have reviewed 35 years experience of extradural haemorrhage (EDH) in a large neurosurgical unit, based in two university hospitals, one dealing exclusively with children and the other a general hospital. A steady reduction in the mortality rate from 29 to 8.5% occurred during that period. A trend towards earlier diagnosis is noted and an increasing proportion of rural patients has been evident throughout the study period. During the time-period studied there were many significant developments: the establishment of a modern neurosurgical unit, the evolution of an intensive care unit, the availability of CT head scanning and the formal organization of rapid retrieval to service country areas. However, no single feature could be identified as the major contributor to falling mortality results. Clinical awareness and early diagnosis are the keys to successful management of EDH.

Adolescent↗
PubMed1991

HLA-Dr expression by tumor cells compared with survival in high grade astrocytomas.

Frozen samples from 78 high grade astrocytomas were reacted with a monoclonal antibody directed against HLA-Dr invariant chain. Survival data was obtained for all 78 cases. HLA-Dr was expressed by a proportion of tumor cells in 65/78 (83%). Comparison of the survival of positive and negative cases showed that the difference was not statistically significant (p = 0.4). The relevance of the finding is discussed in the context of the immunoreaction to brain tumors.

Antigens, Neoplasm↗