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Biomedical subjects

P J Mitchell

Publications and source records attributed to P J Mitchell.

At least 19 recordsLinked to original sources
PubMed2006

The prevalence of vertebral fracture amongst patients presenting with non-vertebral fractures.

INTRODUCTION: Despite vertebral fracture being a significant risk factor for further fracture, vertebral fractures are often unrecognised. A study was therefore conducted to determine the proportion of patients presenting with a non-vertebral fracture who also have an unrecognised vertebral fracture. METHODS: Prospective study of patients presenting with a non-vertebral fracture in South Glasgow who underwent DXA evaluation with vertebral morphometry (MXA) from DV5/6 to LV4/5. Vertebral deformities (consistent with fracture) were identified by direct visualisation using the Genant semi-quantitative grading scale. RESULTS: Data were available for 337 patients presenting with low trauma non-vertebral fracture; 261 were female. Of all patients, 10.4% were aged 50-64 years, 53.2% were aged 65-74 years and 36.2% were aged 75 years or over. According to WHO definitions, 35.0% of patients had normal lumbar spine BMD (T-score -1 or above), 37.4% were osteopenic (T-score -1.1 to -2.4) and 27.6% osteoporotic (T-score -2.5 or lower). Humerus (n=103, 31%), radius-ulna (n=90, 27%) and hand/foot (n=53, 16%) were the most common fractures. For 72% of patients (n=241) the presenting fracture was the first low trauma fracture to come to clinical attention. The overall prevalence of vertebral deformity established by MXA was 25% (n=83); 45% (n=37) of patients with vertebral deformity had deformities of more than one vertebra. Of the patients with vertebral deformity and readable scans for grading, 72.5% (58/80) had deformities of grade 2 or 3. Patients presenting with hip fracture, or spine T-score <or=-2.5, or low BMI, or with more than one prior non-vertebral fracture were all significantly more likely to have evidence of a prevalent vertebral deformity (p<0.05). However, 19.8% of patients with an osteopenic T-score had a vertebral deformity (48% of which were multiple), and 16.1% of patients with a normal T-score had a vertebral deformity (26.3% of which were multiple). Following non-vertebral fracture, some guidelines suggest that anti-resorptive therapy should be reserved for patients with DXA-proven osteoporosis. However, patients who have one or more prior vertebral fractures (prevalent at the time of their non-vertebral fracture) would also become candidates for anti-resorptive therapy-which would have not been the case had their vertebral fracture status not been known. Overall in this study, 8.9% of patients are likely to have had a change in management by virtue of their underlying vertebral deformity status. In other words, 11 patients who present with a non-vertebral fracture would need to undergo vertebral morphometry in order to identify one patient who ought to be managed differently. CONCLUSIONS: Our results support the recommendation to perform vertebral morphometry in patients who are referred for DXA after experiencing a non-vertebral fracture. Treatment decisions will then better reflect any given patient's future absolute fracture risk. The 'Number Needed to Screen' if vertebral morphometry is used in this way would be seven to identify one patient with vertebral deformity, and 14 to identify one patient with two or more vertebral deformities. Although carrying out MXA will increase radiation exposure for the patient, this increased exposure is significantly less than would be obtained if X-rays of the dorso-lumbar spine were obtained.

Absorptiometry, Photon↗
PubMed2006

Short-term effects of methylprednisolone on cerebral volume in multiple sclerosis relapses.

We prospectively investigated the short-term effects of intravenous methyl-prednisolone (IVMP) on cerebral volume in patients suffering a multiple sclerosis (MS) relapse. Ten patients underwent MRI brain studies immediately before and after IVMP treatment, and 4 and 8 weeks later. Whole brain volumes decreased significantly over the 8-week period. The greatest change occurred during IVMP administration. This has implications for MS treatment trials using cerebral atrophy as an endpoint.

Adult↗
PubMed2006

Hemodynamic disturbances associated with endovascular embolization in newborn infants with vein of Galen malformation.

OBJECTIVE: To examine hemodynamic changes following endovascular embolization in newborn infants with vein of Galen malformation and severe cardiac failure in the first week of life. STUDY DESIGN: Over a recent 5-year period, nine such infants were identified. In seven of these infants, changes in arterial blood pressure were analyzed in relation to the timing of embolization procedures. RESULTS: A significant increase in arterial blood pressure was noted after most embolizations. In two infants, this systemic hypertension was severe and treated using intravenous antihypertensive drugs. Both infants subsequently developed complete infarction of both cerebral hemispheres with sparing of the brainstem and cerebellum. Mortality in the nine infants was 33%, and 83% of the survivors were neurologically normal or near normal at follow-up. CONCLUSION: The systemic hypertension observed following endovascular embolizations may provide a protective mechanism to maintain cerebral blood flow after reperfusion injury. Lowering blood pressure in this situation may therefore be detrimental.

Arteriovenous Fistula↗
PubMed2005

Results of a multicentre, randomised controlled trial of intra-arterial urokinase in the treatment of acute posterior circulation ischaemic stroke.

BACKGROUND: Patients with ischaemic stroke due to occlusion of the basilar or vertebral arteries may develop a rapid deterioration in neurological status leading to coma and often to death. While intra-arterial thrombolysis may be used in this context, no randomised controlled data exist to support its safety or efficacy. METHODS: Randomised controlled trial of intra-arterial urokinase within 24 h of symptom onset in patients with stroke and angiographic evidence of posterior circulation vascular occlusion. RESULTS: Sixteen patients were randomised, and there was some imbalance between groups, with more severe strokes occurring in the treatment arm. A good outcome was observed in 4 of 8 patients who received intra-arterial urokinase compared with 1 of 8 patients in the control group. CONCLUSIONS: These results support the need for a large-scale study to establish the efficacy of intra-arterial thrombolysis for acute basilar artery occlusion.

Aged↗
PubMed2005

Cell type-specific and sexually dimorphic expression of transcription factor AP-2 in the adult mouse brain.

Expression of transcription factor AP-2 family genes in adult mouse brain regions was examined at RNA and protein levels and in tissue sections. AP-2 family RNA transcripts, nuclear AP-2 DNA binding activity, and AP-2 immunoreactivity were greatest in hindbrain and midbrain regions. Cells expressing AP-2 were predominantly differentiated neurons and were abundant in the solitary tract nucleus, hypoglossal nucleus, locus coeruleus, cerebellar molecular layer, superior colliculus, mitral cell layers of the main and accessory olfactory bulbs, and in some divisions of the bed nucleus of the stria terminalis. Sexually dimorphic expression of AP-2 was seen in the bed nucleus of the stria terminalis, a forebrain region required for regulation of gender-specific reproductive and social behaviors. In males, AP-2 expressing neurons were present in supracapsular, lateral ventral, and medial ventral divisions of the bed nucleus of the stria terminalis. In contrast, females had AP-2 expressing neurons in the lateral ventral division, but not the supracapsular division, and AP-2 expression in medial ventral division neurons oscillated during the estrus cycle. With the exception of the bed nucleus of the stria terminalis, forebrain regions generally lacked cells with high levels of AP-2. However, a small population of cells co-expressing low levels of AP-2 and Notch1 was sparsely distributed in the cerebral cortex and hippocampal dentate gyrus subgranular zone. Based on their variable levels of NeuN, a marker for differentiated neurons, these cells may include nascent neurons. A subset of cerebellar Purkinje cells also co-expressed low levels of AP-2 and Notch1. Together, the adult brain regions with AP-2 expressing neurons are notable for their importance in pathways that integrate sensory and neuroendocrine information for regulation of reproductive, social, and feeding behaviors. Our data suggest that AP-2 transcription factors contribute at multiple levels to adult brain function including regulation of gender-specific behavior.

Animals↗
PubMed2005

Endovascular treatment of arterial mesenteric ischaemia: a retrospective review.

Mesenteric ischaemia is a condition that has traditionally been managed surgically. It poses a challenging diagnostic and therapeutic problem, particularly in the acute setting. We review a small series of eight patients managed with endovascular techniques for either acute or chronic mesenteric ischaemia at The Royal Melbourne Hospital, from 1997 to 2002. We describe our results and relate these to the recent published literature regarding endovascular and surgical management of mesenteric ischaemia. Our experience confirms the valuable contribution of angioplasty and stenting in chronic mesenteric ischaemia, which compares favourably with surgery with regards to complication rates and mortality. We suggest the need for further studies to compare the long-term efficacy of endovascular techniques compared with surgery in the management of chronic mesenteric ischaemia. Furthermore, we demonstrate a role for endovascular management in acute mesenteric ischaemia, in the appropriate clinical setting.

Acute Disease↗
PubMed2005

Animal models of depressive illness: the importance of chronic drug treatment.

A wide diversity of animal models has been used to examine antidepressant activity. These range from relatively simple models sensitive to acute treatment, to highly sophisticated models that reputedly model some aspect of depressive illness and which yield a positive response to prolonged, chronic, drug treatment. In recent years antidepressant drug research has focused on the search for antidepressant therapy that has a more rapid onset of action. To be relevant, therefore, animal models must measure the time course of drug action. This review examines the claims of animal models to be sensitive to chronic drug treatment and considers their relevance. First, the review addresses the criteria necessary to examine the validity of animal models of depressive illness. Second, those animal models sensitive to chronic antidepressant treatment are reviewed with respect to their validity as animal models of either depressive illness and/or antidepressant activity. In particular, the development and utility of two "ethologically-relevant" animal models, the resident-intruder and social hierarchy paradigms, are described in detail. These models of rodent social and agonistic behaviour demonstrate that acute and chronic treatment with antidepressant drugs (regardless of their acute pharmacological activity) induce diametrically opposite changes in rodent agonistic behaviour. It is argued that the common ability of chronic treatment to increase rodent aggression (which in turn results in increased hierarchical status in closed social groups) most likely reflects the increased assertiveness and associated externalization of emotions expressed during recovery from depressive illness. Finally, findings that relate observed behavioural changes to underlying neurochemical changes are briefly reviewed.

Animals↗
PubMed2004

Subarachnoid haemorrhage due to a dissecting aneurysm of the anterior cerebral artery: a case report.

Dissecting aneurysms of the intracranial carotid circulation are becoming increasingly recognised as a cause of subarachnoid haemorrhage. We present a case where SAH caused by anterior cerebral artery dissection was diagnosed on a repeat angiogram and successfully treated by surgical trapping. Diagnosis may be difficult as angiographic signs may be subtle and variable. Accurate diagnosis and prompt treatment is important, as the re-bleed rate is high.

Adult↗
PubMed2003

Effects of single and repeated electroconvulsive shock on the social and agonistic behaviour of resident rats.

The aim of this study was to determine whether electroconvulsive shock (ECS, an established antidepressant treatment), like acute and chronic antidepressant drug treatments, produces similar differential effects on the behavioural profile of resident rats expressed during social encounters with unfamiliar intruder conspecifics (resident-intruder paradigm). Thirty minute pretreatment with a single ECS suppressed both investigation and aggression directed at intruders concomitant with increased flight behaviour and marked sedation. Behavioural disruption subsided over the following 24 h. In contrast, resident rats subjected to bi-daily ECS treatment expressed elevated aggression at days 7 (four shocks) and 14 (eight shocks). Eight days after the last ECS treatment the behaviour of the resident rats had returned to pretreatment values. Additional studies showed that bi-daily ECS treatment nearly abolished 5-HT(2C) receptor-mediated hypolocomotion induced by acute m-chlorophenylpiperazine (mCPP, 2.5 mg/kg sc) challenge 24 h following 2 ECSs, while 4 ECSs only enhanced 5-HT(2A) receptor-mediated head shakes induced by 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 2.0 mg/kg sc). These studies demonstrate that repeated ECS treatment increases the aggressive behaviour of resident rats which may be associated with adaptive changes in 5-HT(2C) and 5-HT(2A) receptor-mediated function. It remains to be seen whether adaptive changes in 5-HT(2C) receptor function represent a common mechanism of clinical antidepressant efficacy.

Agonistic Behavior↗
PubMed2003

Actinide analysis of a depleted uranium penetrator from a 1999 target site in southern Serbia.

Following the detection of 236U in depleted uranium (DU) ammunition used during the Balkans conflict in the 1990s, concern has been expressed about the possibility that other nuclides from the nuclear fuel cycle and, in particular, transuranium nuclides, might be present in this type of ammunition. In this paper, we report the results of uranium and plutonium analyses carried out on a depleted uranium penetrator recovered from a target site in southern Serbia. Our data show the depleted nature of the uranium and confirm the presence of trace amounts of plutonium in the penetrator. The activity concentration of (239+240)PU, at 45.4+/-0.7 Bq kg(-1), is the highest reported to date for any penetrator recovered from the Balkans. This concentration, however, is comparable to that expected to be present naturally in uranium ores and, from a radiological perspective, would only give rise to a very small increase in dose to exposed persons compared to that from the DU itself.

Environmental Exposure↗
PubMed2002

Manometry combined with cervical puncture in idiopathic intracranial hypertension.

OBJECTIVE: To determine by cerebral venography and manometry in patients with idiopathic intracranial hypertension the cause of the previously demonstrated venous hypertension in the superior sagittal and proximal transverse sinuses. METHODS: Cerebral venous sinus pressure was measured before and immediately after C1-2 puncture with removal of 20 to 25 mL of CSF. RESULTS: Lowering the intracranial pressure by lateral C1-2 puncture during manometry has shown that the venous hypertension resolves immediately. CONCLUSION: These studies indicate that the venous hypertension is due to compression of the transverse sinuses by raised intracranial pressure and not due to a primary obstructive process in the cerebral venous sinuses.

Brain↗
PubMed2002

The validity of animal models of predisposition to depression.

Some animal models of depression, including the majority of the more recently introduced models, are better characterized as models of predisposition to depression. In the first part of this paper, we show that the basis for such a model could be either a procedure that increases the ease with which an analogue of major depression may be evoked, or a presentation analogous to dysthymia (chronic mild depression). We then consider how the concepts of predictive, face, and construct validity apply to such models. Next, we review the validity of the available models of predisposition to depression, which derive from genetics, genomics, developmental manipulations, and brain lesioning. Finally, we compare the performance of the different models, using a novel scoring system that formalizes the evaluation of animal models against each of the three sets of validation criteria.

Animals↗
PubMed2002

Clinical course and medical management of neonates with severe cardiac failure related to vein of Galen malformation.

BACKGROUND: Neonatal presentation of vein of Galen aneurysmal malformations (VGAMs) with intractable cardiac failure is considered a poor prognostic sign. Interventional neuroradiology with embolisation has been shown to control cardiac failure, but there is a perception that neurological outcome in survivors is poor. OBJECTIVE: To determine if aggressive intensive care and anaesthetic management of cardiac failure before urgent embolisation can influence morbidity and mortality. PATIENTS: Nine newborns (four boys, five girls) were diagnosed with symptomatic vein of Galen malformations in the neonatal period during the period 1996-2001. Eight developed intractable high output cardiac failure requiring initial endovascular treatment in the first week of life. RESULTS: The immediate outcome after a series of endovascular procedures was control of cardiac failure and normal neurological function in six (66%) patients, one death from intractable cardiac failure in the neonatal period, and two late deaths with severe hypoxic-ischaemic neurological injury (33% mortality). Clinical review at 6 months to 4 years of age showed five infants with no evidence of neurological abnormality or cardiac failure and one child with mild developmental delay (11%). CONCLUSIONS: Aggressive medical treatment of cardiac failure and early neurointervention combined with modern neuroanaesthetic care results in good survival rates with low morbidity even in cases of high risk VGAM presenting in the immediate perinatal period with cardiac failure. Systemic arterial vasodilators improve outcome in neonates with cardiac failure secondary to VGAM. Excessive beta adrenergic stimulation induced by conventional inotropic agents may exacerbate systemic hypoperfusion.

Cardiac Output, Low↗
PubMed2001

Developmental regulation and overexpression of the transcription factor AP-2, a potential regulator of the timing of Schwann cell generation.

There is now evidence from in vivo and in vitro studies that the rate of Schwann cell generation is regulated by the balance of two opposing signals, beta neuregulins and endothelins. The beta neuregulins promote the development of precursors to Schwann cells whereas endothelins retard it through an action on endothelin-B receptors. The present work has shown additional controls of this transition, and implicates AP-2 transcription factors, in particular AP-2 alpha, as negative regulators of Schwann cell generation. We found that both AP-2 alpha and AP-2 gamma are present in early embryonic nerves, whereas AP-2 beta was not. Isoform-specific analysis of AP-2 alpha showed that isoform 3 was most abundant with isoforms 1 and 2 present in lesser amounts; isoform 4 was absent. Maximal AP-2 alpha and AP-2 gamma mRNA expression occurred at embryonic day (E) 12/13 in the mouse and at E14/15 in the rat, which correlates with the presence of Schwann cell precursors in the nerve. In both rats and in mice, in vivo and in vitro, downregulation of AP-2 alpha mRNA and protein coincided with one of the main steps in Schwann cell development, the precursor-Schwann cell transition. Moreover, Schwann cell generation was delayed if this downregulation was prevented by enforced expression of AP-2 alpha in precursors. These studies suggest that AP-2 is involved in the control of the timing of Schwann cell development.

Animals↗
PubMed2001

Tandem lesions of the carotid circulation: combined extracranial endarterectomy and intracranial transluminal angioplasty.

A case series is presented demonstrating a unique approach to the treatment of tandem atherosclerotic lesions of the internal carotid artery. Between 1994 and 1999 eight patients with tandem lesions of the internal carotid artery were treated by combined carotid endarterectomy for the proximal lesion and intraoperative angioplasty of the distal intracranial lesion via the carotid arteriotomy. The success and complication rates were evaluated. A 100% technical success rate was achieved with one post procedural complication by ipsilateral stroke within 24 h. The advantages of this technique include the treatment of tandem lesions by the one procedure, improved transluminal access to the intracranial lesion and the ability to reduce the risk of embolism by flow control during balloon inflation.

Aged↗
PubMed2001

Treatment of renovascular disease with percutaneous stent insertion: long-term outcomes.

Renal artery stenosis is a common, progressive cause of hypertension and renal impairment, and is frequently treated with percutaneous transluminal dilatation and stenting. The outcome of this procedure is still being evaluated. The records of 198 consecutive patients who had stents inserted at the Royal Melbourne Hospital were analysed retrospectively, and adequate follow-up information on 148 (75%), in whom a total of 182 renal arteries had been treated was obtained. Technical success was achieved in 144 patients (97%). Complications occurred in 19 patients (13.3%), with major complications occurring in 10 (7.0%) and one death occurring in relation to the procedure. A fall in average systolic blood pressure of 13.2 mmHg (12.1-14.3 mmHg) was seen and a fall in diastolic blood pressure of 10.1 mmHg (9.3-10.9 mmHg), without an increase in the number of antihypertensive drugs used. Renal function remained stable in the majority of patients, particularly those who had minimal baseline renal impairment. Restenosis was common after 6 months, occurring eventually in 29% of screened patients, but was not shown to affect clinical outcomes. Insertion of renal artery stents is a safe and effective treatment for renal artery stenosis.

Angioplasty, Balloon↗