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Biomedical subjects

R J Forsyth

Publications and source records attributed to R J Forsyth.

At least 19 recordsLinked to original sources
PubMed2006

Monoaminergic agonists for acute traumatic brain injury.

BACKGROUND: Although there have been considerable gains in understanding the cascade of events that lead to secondary injury after traumatic brain injury (TBI), efforts to translate this understanding into new therapeutic, so-called neuroprotective approaches, have so far proven disappointing. As an alternative, there is growing interest in approaches to enhance brain repair after injury. Animal models suggest that agents enhancing monoaminergic (MA) transmission, particularly amphetamines, promote motor recovery from focal brain injury and it is proposed that this might represent a complementary means of therapeutic intervention in the later post-injury phase. OBJECTIVES: To evaluate the evidence that MAs improve final outcome after TBI. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library, Issue 2, 2005), the Cochrane Injuries Group's Specialised Register (to May 2005), MEDLINE (1966 to May 2005), EMBASE (1980 to May 2005) and the Science Citation Index (1992 to June 2005). We contacted researchers and authors of published and unpublished trials. Searches were updated in May 2005. SELECTION CRITERIA: Randomised controlled trials comparing the use of a MA (together with conventional non-pharmacological rehabilitative therapy) versus conventional non-pharmacological rehabilitative therapy alone. DATA COLLECTION AND ANALYSIS: Two authors independently screened records, extracted data and assessed trial quality. MAIN RESULTS: Although there is a limited clinical literature addressing this topic, none of the studies identified fully met inclusion criteria for this review. AUTHORS' CONCLUSIONS: At present there is insufficient evidence to support the routine use of MAs to promote recovery after TBI.

Acute Disease↗
PubMed2006

Participation of disabled children: how should it be characterised and measured?

PURPOSE: The aim of the paper is to explore the issues involved in measuring children's participation. METHOD: The concept of participation as encapsulated in the International Classification of Functioning, Disability and Health (ICF) is discussed as it applies to children. The essential components of any measure of children's participation are outlined, including participation essential for normal development and survival, leisure activities, and educational participation. Some existing instruments are briefly reviewed in terms of their coverage of the essential components and the adequacy of their approach to measurement. RESULTS: Key issues regarding the content of an adequate measure of participation include the need to consider the child's dependency on the family, and their changing abilities and autonomy as they grow older. Instruments may be most appropriate where they ask the child directly, implying use of visual as well as verbal presentation. Their focus should be on 'performance' such as whether and how often an activity is taken part in, and not incorporate degree of assistance within the measurement scaling. CONCLUSIONS: Currently available measures of children's participation all have some limitations in terms of their applicability across impairment groupings, whether the child can directly respond, and in the ICF components covered. The feasibility of developing measurement instruments of children's participation at different ages is discussed.

Activities of Daily Living↗
PubMed2006

Severe head injury in children: emergency access to neurosurgery in the United Kingdom.

OBJECTIVE: To determine the scale of acute neurosurgery for severe traumatic brain injury (TBI) in childhood, and whether surgical evacuation for haematoma is achieved within four hours of presentation to an emergency department. METHODS: A 12 month audit of emergency access to all specialist neurosurgical and intensive care services in the UK. Severe TBI in a child was defined as that necessitating admission to intensive care. RESULTS: Of 448 children with severe head injuries, 91 (20.3%) underwent emergency neurosurgery, and 37% of these surgical patients had at least one non-reactive and dilated pupil. An acute subdural or epidural haematoma was present in 143/448 (31.9%) children, of whom 66 (46.2%) underwent surgery. Children needing surgical evacuation of haematoma were at a median distance of 29 km (interquartile range (IQR) 11.8-45.7) from their neurosurgical centre. One in four children took longer than one hour to reach hospital after injury. Once in an accident and emergency department, 41% took longer than fours hours to arrive at the regional centre. The median interval between time of accident and arrival at the surgical centre was 4.5 hours (IQR 2.23-7.73), and 79% of inter-hospital transfers were undertaken by the referring hospital rather than the regional centre. In cases where the regional centre undertook the transfer, none were completed within four hours of presentation-the median interval was 6.3 hours (IQR 5.1-8.12). CONCLUSIONS: The system of care for severely head injured children in the UK does not achieve surgical evacuation of a significant haematoma within four hours. The recommendation to use specialist regional paediatric transfer teams delays rather than expedites the emergency service.

Adolescent↗
PubMed2005

Critical thresholds of intracranial pressure and cerebral perfusion pressure related to age in paediatric head injury.

BACKGROUND: The principal strategy for managing head injury is to reduce the frequency and severity of secondary brain insults from intracranial pressure (ICP) and cerebral perfusion pressure (CPP), and hence improve outcome. Precise critical threshold levels have not been determined in head injured children. OBJECTIVE: To create a novel pressure-time index (PTI) measuring both duration and amplitude of insult, and then employ it to determine critical insult thresholds of ICP and CPP in children. METHODS: Prospective, observational, physiologically based study from Edinburgh and Newcastle, using patient monitored blood pressure, ICP, and CPP time series data. The PTI for ICP and CPP for 81 children, using theoretical values derived from physiological norms, was varied systematically to derive critical insult thresholds which delineate Glasgow outcome scale categories. RESULTS: The PTI for CPP had a very high predictive value for outcome (receiver operating characteristic analyses: area under curve = 0.957 and 0.890 for mortality and favourable outcome, respectively) and was more predictive than for ICP. Initial physiological values most accurately predicted favourable outcome. The CPP critical threshold values determined for children aged 2-6, 7-10, and 11-15 years were 48, 54, and 58 mm Hg. respectively. CONCLUSIONS: The PTI is the first substantive paediatric index of total ICP and CPP following head injury. The insult thresholds generated are identical to age related physiological values. Management guidelines for paediatric head injuries should take account of these CPP thresholds to titrate appropriate pressor therapy.

Adolescent↗
PubMed2005

Epidemiology of traumatic brain injury in children receiving intensive care in the UK.

AIMS: To describe the epidemiology of children with traumatic brain injury (TBI) admitted to paediatric intensive care units (PICUs) in the UK. METHODS: Prospective collection of clinical and demographic information from paediatric and adult intensive care units in the UK and Eire between February 2001 and August 2003. RESULTS: The UK prevalence rate for children (0-14 years) admitted to intensive care with TBI between February 2001 and August 2003 was 5.6 per 100,000 population per year (95% Poisson exact confidence intervals 5.17 to 6.05). Children admitted to PICUs with TBI were more deprived than the population as a whole (mean Townsend score for TBI admissions 1.19 v 0). The commonest mechanism of injury was a pedestrian accident (36%), most often occurring in children over 10. There was a significant summer peak in admissions in children under 10 years. Time of injury peaked in the late afternoon and early evening, a pattern that remained constant across the days of the week. Injuries involving motor vehicles have the highest mortality rates (23% of vehicle occupants, 12% of pedestrians) compared with cyclists (8%) and falls (3%). In two thirds of admissions (65%) TBI was an isolated injury. CONCLUSIONS: TBI in children requiring intensive care is more common in those from poorer backgrounds who have been involved in accidents as pedestrians. The summer peak in injury occurrence for 0-10 year olds and late afternoon timing give clear targets for community based injury prevention.

Accidents, Traffic↗
PubMed2005

A case of infant botulism with a possible link to infant formula milk powder: evidence for the presence of more than one strain of Clostridium botulinum in clinical specimens and food.

Infant botulism was confirmed in a 5-month-old female by both isolation of Clostridium botulinum type B and by detection of type B botulinum neurotoxin in rectal washout and faeces. DNA fingerprinting of nine isolates from faeces yielded two different amplified-fragment length polymorphism (AFLP) patterns. C. botulinum was isolated from two of 14 food and drink items from the patient's home: C. botulinum type A was recovered from an opened container of dried rice pudding and C. botulinum type B from opened infant formula milk powder. Ten C. botulinum type B isolates from the opened infant formula yielded four AFLP patterns, two of which were indistinguishable from the clinical isolates. Fifteen unopened foods were tested and C. botulinum type B of a unique AFLP pattern was recovered from one unopened infant formula of the same batch as the opened container. It is suggested that multiple C. botulinum were present in both food and the intestine during infant botulism.

Botulinum Toxins↗
PubMed2001

Incidence, aetiology, and outcome of non-traumatic coma: a population based study.

AIM: To determine the incidence, presentation, aetiology, and outcome of non-traumatic coma in children aged between 1 month and 16 years. METHODS: In this prospective, population based, epidemiological study in the former Northern NHS region of the UK, cases were notified following any hospital admission or community death associated with non-traumatic coma. Coma was defined as a Glasgow Coma Score below 12 for more than six hours. RESULTS: The incidence of non-traumatic coma was 30.8 per 100 000 children under 16 per year (6.0 per 100 000 general population per year). The age specific incidence was notably higher in the first year of life (160 per 100 000 children per year). CNS specific presentations became commoner with increasing age. In infants, nearly two thirds of presentations were with non-specific, systemic signs. Infection was the commonest overall aetiology. Aetiology remained unknown in 14% despite extensive investigation and/or autopsy. Mortality was highly dependent on aetiology, with aetiology specific mortality rates varying from 3% to 84%. With follow up to approximately 12 months, overall series mortality was 46%.

Adolescent↗
PubMed2001

Cognitive and adaptive outcomes and age at insult effects after non-traumatic coma.

Cognitive and adaptive behavioural outcome were studied in the identified survivors of a population based study of non-traumatic coma (NTC) in childhood. Children were assessed early (six weeks) and late (12 months) after NTC. At least 7% of those children in whom no suspicions of prior neurodevelopmental morbidity existed showed moderate or severe disability following NTC. Children over 2 years of age at insult showed some improvement between early and late assessments; however, children below 2 years showed no improvement. Differing age at insult effects were observed between aetiological groups. A relation between early age at first insult and poor outcome was particularly evident among children experiencing NTC caused by epilepsy.

Adaptation, Psychological↗
PubMed1999

Compatibility of tirofiban HCl with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride during simulated Y-site administration.

OBJECTIVE: To study the compatibility of tirofiban HCl injection 0-05 mg/ml with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride infusion solutions during simulated Y-site administration. METHOD: Tirofiban HCl, dopamine HCl, famotidine, lidocaine HCl and potassium chloride infusions were each prepared from their respective concentrates as per current clinical preparation instructions in both 0.9% sodium chloride and 5% dextrose solutions at both the minimum and maximum concentrations normally administered. Sodium heparin premixed infusion solutions in 5% dextrose and 0-45% sodium chloride were used as-is. Tirofiban HCl solutions were combined 1:1 (simulated Y-site administration) with the dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride solutions in separate glass containers and polyvinylchloride Y-site infusion lines. Samples were held for 4 h at room temperature under ambient fluorescent light and were assayed for changes in drug content, degradation, pH, appearance and turbidity. Activity of sodium heparin solutions was measured using an aPTT coagulation assay. RESULTS: All mixtures remained clear and colourless with no visual indication of instability, i.e. precipitation. Clarity of solutions was confirmed by turbidometric analysis. There was no significant loss of drug, increase in known degradates, or appearance of unknown drug-related peaks as determined by HPLC. The activity of heparin in heparin-containing solutions remained unchanged. The pH of all test-solutions remained constant. CONCLUSION: Tirofiban HCl injection 0.05 mg/ml can be co-infused by Y-site administration with dopamine HCl, famotidine, sodium heparin, lidocaine HCl and potassium chloride injection solutions.

Chromatography, High Pressure Liquid↗
PubMed1998

Solid-phase extraction and liquid chromatographic quantitation of the antiarrhythmic drug L-768673 in a microemulsion formulation.

A sensitive and specific method based in solid-phase extraction and reverse-phase liquid chromatography was developed and validated for the quantitation of L-768673 in a microemulsion formulation. Following a water wash, the drug was eluted from the extraction column with acetonitrile and was analyzed on a reverse-phase C18 column with UV detection at 245 nm. The mobile phase consisted of acetonitrile-0.2% trifluoroacetic acid, 0.1% triethylamine (53:47 v/v). The retention time L-768673 was approximately 28 min with a flow rate of 1.5 ml min-1.

Acetamides↗
PubMed1996

The mechanisms controlling physiologically stimulated changes in rat brain glucose and lactate: a microdialysis study.

1. This study is concerned with the supply of metabolic substrates for neuronal metabolism. Experiments were carried out to investigate whether mechanisms demonstrated in cultured astrocytes also occurred in vivo; these were cAMP-mediated breakdown of glycogen and glutamate uptake-stimulated release of lactate. 2. In vivo microdialysis was used in freely moving rats. Lactate and glucose in the dialysate were assayed using enzyme-based on-line assays. Drugs were given locally through the dialysis probe. Regional cerebral blood flow was measured using the hydrogen clearance method. 3. There was an increase in dialysate glucose in response to the beta-adrenoceptor agonist isoprenaline and to 8-bromo-cAMP, an analogue of cAMP, the second messenger of beta-adrenoceptor stimulation. The effect of isoprenaline was blocked by the antagonist propranolol. Isoprenaline had no effect on dialysate lactate, which was increased by the glutamate uptake blocker beta-D,L-threohydroxyaspartate (THA). 4. Physiological stimulation of neuronal activity produced an increase in both lactate and glucose. The increase in lactate was depressed in the presence of THA but was unaffected by propranolol. The increase in glucose was blocked by propranolol. Regional cerebral blood flow was increased by physiological stimulation but was unaffected by propranolol. 5. These results demonstrate that physiologically stimulated increases in glucose and lactate in the brain are mediated by different mechanisms.

Adrenergic beta-Agonists↗
PubMed1996

Astrocytes and the delivery of glucose from plasma to neurons.

Conventional kinetic models of brain glucose uptake and metabolism that visualize brain glucose as being in a single pool in equilibrium with plasma, are unable to account for some recently described experimental findings. These include microdialysis demonstrations of a brain extracellular fluid glucose concentration that is both low, and significantly affected by changes in neuronal activity; and observations of transient glucose export (transient negative whole-brain arteriovenous differences) in certain neuro-intensive care settings. A kinetic model that treats brain glucose as divided into more than one, kinetically distinct, compartment, implying the presence of a glucose "reservoir" behind the blood-brain barrier, and with plasma glucose initially entering a compartment other than the brain extracellular fluid, is more consistent with these experimental observations. Neuroanatomical considerations suggest that plasma glucose may initially exchange with an intracellular astrocytic glucose pool, rather than the brain extracellular fluid. Astrocyte glycogen, mobilized at times of increased neuronal activity, could form the reservoir whose presence is inferred from demonstrations of transient glucose export, but only if glycogenolytic products can be exported from astrocytes as glucose. This hypothesis is considered in the light of the frequently suggested concept of a "nutritional" role for perivascular astrocytes and invertebrate glia, taking up blood-borne glucose and passing on metabolic substrates to neurons. The implications of this model for 2-deoxyglucose-based methods for regional cerebral metabolic rate estimation are discussed. In general, errors due to the approximations inherent in the conventional three compartment kinetic model, may be expected to become less significant as metabolism is averaged over space and time. Thus the three-compartment model is probably acceptable for the description of metabolism at the relatively low spatial and temporal resolution of these techniques.

Animals↗
PubMed1996

Dephosphorylation of 2-deoxyglucose 6-phosphate and 2-deoxyglucose export from cultured astrocytes.

Neurotransmitter-stimulated mobilization of astrocyte glycogen has been proposed as a basis for local energy homeostasis in brain. However, uncertainty remains over the fate of astrocyte glycogen. Upon transfer of cultured astrocytes pre-loaded with [2-3H]2-deoxyglucose 6-phosphate at non-tracer concentrations to a glucose-free, 2-deoxyglucose-free medium, rapid dephosphorylation of a proportion of the intracellular 2-deoxyglucose 6-phosphate pool and export of 2-deoxyglucose to the extracellular fluid occurs. Astrocytes show very low, basal rates of gluconeogenesis from pyruvate (approx. 1 nmol mg protein-1 h-1). Astrocytes in vivo may be capable of physiologically significant glucose export from glucose-6-phosphate. The low gluconeogenic activity in astrocytes suggests that the most likely source of glucose-6-phosphate may be glycogen. These findings support the hypothesis that export, as glucose, to adjacent neurons may be one of the possible fate(s) of astrocytic glycogen. Such export of glycogen as glucose occurring in response to increases in neuronal activity could contribute to energy homeostasis on a paracrine scale within brain.

Animals↗
PubMed1994

Glucose export from the brain in man: evidence for a role for astrocytic glycogen as a reservoir of glucose for neural metabolism.

We report transients of net export of glucose from brain with jugular venous glucose content exceeding arterial by up to 5.3 mmol.l-1 in 19 children undergoing cardiopulmonary bypass surgery. The magnitude of the release implies the presence of a glucose reservoir in brain, the most likely candidate being astrocytic glycogen. These data provide evidence that astrocytic glycogen can be exported as glucose, permitting spatial and temporal modulation of glucose delivery to neurons.

Astrocytes↗
PubMed1994

Determination of bisphosphonate drugs in pharmaceutical dosage formulations by ion chromatography with indirect UV detection.

Application of ion chromatography (IC) to the analysis of non-chromophoric bisphosphonate drugs in pharmaceutical dosage formulations is described. The method is based on the use of single-column ion chromatography in conjunction with indirect UV detection that obviates the need for tedious chemical derivatization procedures. Diluted drug samples are chromatographed directly on a Waters IC-Pak HR anion-exchange column with dilute nitric acid (1.6-12 mM) as the mobile phase which exhibits a UV absorption maximum near 220 nm. Analyte detection is monitored by measuring the decrease in absorption of the mobile phase. The IC method has been validated and shown to be precise, accurate, specific and rugged for routine assay. Application of the method to the determination of alendronate sodium tablets, etidronate disodium injectable (which requires an eluent pH control for chromatographic resolution of active drug from chloride ions) and clodronate disodium injectable is presented. The performances of the Waters IC-Pak HR and several equivalent columns are also discussed.

Alendronate↗
PubMed1994

Determination of imipenem and cilastatin sodium in Primaxin by first order derivative ultraviolet spectrophotometry.

A UV-spectrophotometric assay to measure the concentrations of the active drug components (imipenem and cilastatin) or Primaxin for routine release testing is described. The assay is based on the use of first order derivative spectrophotometry. The trough amplitudes in the first derivative spectrophotometric spectra at 243 and 318 nm were selected to determine cilastatin and imipenem, respectively. A linear relationship (R > 0.99) between the trough amplitudes and concentrations was demonstrated over the range 14-42 micrograms ml-1 for both drug components. Commercial IV formulations and laboratory prepared mixtures containing both drugs in different proportions were assayed using the developed method with good recoveries (ave. 100.6%). The method is rapid, precise, accurate and was shown to be equivalent to the more time consuming LC method; which is currently used for routine release testing. The specificity and stability indicating properties of the method will also be addressed.

Buffers↗