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Biomedical subjects

J Cannon

Publications and source records attributed to J Cannon.

At least 19 recordsLinked to original sources

Normalized lengthening peak torque is associated with temporal twitch characteristics in elderly women but not young women.

AIM: To determine if greater normalized torque during maximal effort lengthening actions in elderly women compared with young women is related to age-associated adjustments in neural activation and/or contractile function. METHODS: The right knee extensors of 14 young women (21-30 years) and 12 elderly women (65-78 years) were assessed for isometric, shortening and lengthening peak torque, electromyography (EMG) activity, and isometric twitch contractile properties. Knee extensor contractile tissue volume was determined using magnetic resonance imaging. RESULTS: Normalized torque was determined as peak torque per unit of knee extensor contractile tissue volume. Normalized torque during the isometric and shortening actions was similar between age groups (P > 0.05); however, lengthening normalized torque was significantly higher for the elderly women (P < 0.05). In the young women, a significant relationship existed between normalized torque and EMG for all muscle actions (P < 0.05), while no association was found between normalized torque and temporal twitch characteristics for any muscle action (P > 0.05). In the elderly women, a significant relationship existed between normalized torque and EMG for the isometric and shortening muscle actions (P < 0.05), but not for lengthening normalized torque and EMG (P > 0.05). Furthermore, no association existed between isometric and shortening normalized torque, and temporal twitch characteristics in the elderly women (P > 0.05); however, a significant relationship existed between lengthening normalized torque, and the rate of relaxation and contraction duration (P < 0.05). CONCLUSIONS: The greater capacity to develop lengthening peak torque relative to contractile tissue volume in the elderly women appeared to be associated with age-related adjustments in the temporal twitch characteristics rather than neural activation.

Adult↗

Occupational asthma caused by cellulase and lipase in the detergent industry.

Three employees from two different detergent companies were investigated for occupational asthma, using skin prick tests, serum specific IgE, and specific bronchial challenge. Two were challenged with lipase and one with cellulase. All three cases had immunological evidence of sensitisation to the detergent enzymes with which they worked. Bronchial challenge in each provoked a reproducible dual asthmatic response, which reproduced their work related symptoms. These are the first reported cases of occupational asthma attributable to cellulase and lipase in the detergent industry. Four of the most common enzymes used in this industry have now been reported to cause occupational asthma; continued vigilance and caution are needed when working with these or other enzymes.

Adult↗

Age, diet and injury affect the survival of facial motoneurons.

Using the model of facial nerve avulsion, we have compared the effects of injury, age and diet on motoneuronal survival. One to four weeks after nerve avulsion, 50-75% motoneuron loss was quantified in ad libitum-fed rats aged 7 days (neonate), 6 months (adult) and 24 months (aging) at the time of injury. Evidence of apoptosis was found for neonatal rats at 3 days post-injury, but not for neonates examined 7 days or adult or aging rats examined 1 month after injury. Non-operated, ad libitum-fed rats showed no significant loss of facial motoneurons by 24 months. Surprisingly, non-operated rats whose food intake was restricted to 15 g standard rat chow per day from the age of 6 months lost 50% of their motoneurons by 24 months. Facial nerve avulsion of 24-month-old rats raised on this restricted diet did not result in any additional loss of motoneurons one month after injury. These results challenge the common view that aging results in neuronal loss and that dietary restriction is universally beneficial.

Aging↗

A reproducible and variable intensity cycling performance protocol for warm conditions.

This study was undertaken to assess the reproducibility of a variable intensitycycling protocol using subjects of varying abilities, under warm humid conditions. Eleven subjects (Age 21.4+/-2.6 years; VO2peak 3.30+/-0.9 l x min(-1); peak power 322.8+/-86.3 W; mean+/-SD) performed a 60 min cycling trial punctuated with six one-min "all-out" sprints at 10-min intervals on three occasions 5-14 days apart. Ambient temperature and relative humidity were set at 33+/-0.7 degrees C and 63+/-2.0%, respectively. Subjects used their own bicycle mounted to an electromagnetic trainer and were only permitted to monitor elapsed time and heart rate. Repeatability was assessed using the limits of agreement which were best between trials 2 and 3 where the distance cycled was -0.54 km below and 1.34 km above the distance cycled for trial 2. The co-efficient of variation (CV) for distance for three trials was 3.58%. For trials 1 and 2 the CV was 3.54% (r = 0.97, p< 0.001) decreasing to 1.34% (r = 0.99, p< 0.001) for trials 2 and 3. The intra-class correlation for three trials was 0.93. Distance for trial 1 (26.3+/-5.0 km; p< 0.05) was less than trials 2 (27.7+/-5.7 km) and 3 (28.1+/-5.6 km). It was concluded that repeatability for this performance protocol with cyclists of varying abilities In warm humid conditions was acceptable given at least one familiarisation trial. However, it is not yet known whether other protocols designed for moderate environments are applicable to less favorable conditions. Further studies are needed before results of treatment effects under differing ambient conditions can be fully understood and assigned appropriate significance.

Adult↗

Ethanol impairs insulin-stimulated mitochondrial function in cerebellar granule neurons.

Ethanol impairs insulin-stimulated survival and mitochondrial function in immature proliferating neuronal cells due to marked inhibition of downstream signaling through P13 kinase. The present study demonstrates that, in contrast to immature neuronal cells, the major adverse effect of chronic ethanol exposure (50 mM) in post-mitotic rat cerebellar granule neurons is to inhibit insulin-stimulated mitochondrial function (MTT activity, MitoTracker Red fluorescence, and cytochrome oxidase immunoreactivity). Ethanol-impaired mitochondrial function was associated with increased expression of the p53 and CD95 pro-apoptosis genes, reduced Calcein AM retention (a measure of membrane integrity), increased SYTOX Green and propidium iodide uptake (indices of membrane permeability), and increased oxidant production (dihydrorosamine fluorescence and H2O2 generation). The findings of reduced membrane integrity and mitochondrial function in short-term (24 h) ethanol-exposed neurons indicate that these adverse effects of ethanol can develop rapidly and do not require chronic neurotoxic injury. A role for caspase activation as a mediator of impaired mitochondrial function was demonstrated by the partial rescue observed in cells that were pre-treated with broad-spectrum caspase inhibitors. Finally, we obtained evidence that the inhibitory effects of ethanol on mitochondrial function and membrane integrity were greater in insulin-stimulated compared with nerve growth factor-stimulated cultures. These observations suggest that activation of insulin-independent signaling pathways, or the use of insulin sensitizer agents that enhance insulin signaling may help preserve viability and function in neurons injured by gestational exposure to ethanol.

Amino Acid Chloromethyl Ketones↗

Ageing is not associated with a decline in neuromuscular innervation or reduced specific force in men aged 20 and 50 years.

The exact mechanisms responsible for the decline in strength with age are yet to be completely elucidated. Three proposed mechanisms responsible for the detrimental effect of increasing age on strength include changes in muscle mass, specific force and/or neuromuscular innervation. Thus, the purpose of this investigation was to determine if the age-related reduction in peak isometric strength was primarily associated with changes in muscle cross-sectional area, neuromuscular innervation and/or specific force. The cross-sectional area of the knee extensor muscles (QCSA) was estimated in 13 younger men (YM; 20.8 +/- 1.6 years) and eight middle-aged men (MM; 53.8 +/- 4.2 years) prior to performing a series of four maximal voluntary isometric contractions on an isokinetic dynamometer at an angle of 60 degrees knee flexion. Peak force was determined and surface electromyography was sampled from the rectus femoris muscle during each maximal voluntary contraction. The cross-sectional area of the knee extensor muscles, peak force and integrated electromyography (IEMG) were significantly lower in the MM (P<0.01). However, when peak force and peak IEMG values were corrected for QCSA, there were no significant differences between age groups. These results suggest that the reduction in peak isometric force observed in the MM was primarily associated with quantitative changes in muscle mass, rather than reduced neuromuscular innervation or specific force. Therefore, preserving muscle mass through resistance training may significantly reduce the age-associated differences in peak strength and assist in promoting quality of life and functional independence in older adults.

Adult↗

Power transcranial Doppler ultrasound in the detection of intracranial aneurysms.

BACKGROUND AND PURPOSE: We sought to perform a large, prospective, multicenter, blinded study comparing power transcranial color duplex sonography (power TCDS) with intra-arterial digital subtraction angiography (IADSA) in the detection of intracranial aneurysms. METHODS: Contemporaneous TCDS and IADSA examinations were performed in 171 subjects with suspected intracranial aneurysm. Via the temporal bone window, a 2-dimensional hand-held noncontrast transcranial duplex ultrasound imaging system was used operating in power and spectral modes. Sonographers were blinded to clinical history and results of brain CT and IADSA. RESULTS: We found that 157 subjects (92%) had an adequate bone window. Sensitivity per patient was 0.78 (95% CI, 0.66 to 0.87) and 0.46 (95% CI, 0.36 to 0.56) for any anterior circulation aneurysms. Sensitivity was 0.35 (95% CI, 0.24 to 0.46) for aneurysms </=5 mm and 0.81 (95% CI, 0.62 to 0.94) for aneurysms >5 mm. Accuracy was lower for aneurysms on the cavernous and terminal internal carotid arteries, including posterior communicating artery origin (0.71; 95% CI, 0.63 to 0.79), than for those on the anterior (0.82; 95% CI, 0.74 to 0.89) or the middle cerebral arteries (0.79; 95% CI, 0.71 to 0.86). CONCLUSIONS: Power TCDS is a promising, inexpensive, noninvasive test for anterior circulation intracranial aneurysms but is less sensitive per aneurysm than alternatives such as CT angiography or MR angiography. Sensitivity is poor for aneurysms </=5 mm in diameter. The internal carotid artery is the most difficult segment to interpret.

Adult↗

Oxidative stress and hypoxia-like injury cause Alzheimer-type molecular abnormalities in central nervous system neurons.

Neuronal loss and neuritic/cytoskeletal lesions (synaptic disconnection and proliferation of dystrophic neurites) represent major dementia-associated abnormalities in Alzheimer's disease (AD). This study examined the role of oxidative stress as a factor contributing to both the cell death and neuritic degeneration cascades in AD. Primary neuron cultures were treated with H2O2 (9-90 microM) or desferrioxamine (2-25 microM) for 24 h and then analyzed for viability, mitochondrial mass, mitochondrial function, and pro-apoptosis and sprouting gene expression. H2O2 treatment causes free-radical injury and desferrioxamine causes hypoxia-type injury without free radical generation. The H2O2-treated cells exhibited sustained viability but neurite retraction, impaired mitochondrial function, increased levels of the pro-apoptosis gene product CD95/Fas, reduced expression of N2J1-immunoreactive neuronal thread protein and synaptophysin, and reduced distribution of mitochondria in neuritic processes. Desferrioxamine treatment resulted in dose-dependent neuronal loss associated with impaired mitochondrial function, proliferation of neurites, and reduced expression of GAP-43, which has a role in path-finding during neurite outgrowth. The results suggest that oxidative stress can cause neurodegeneration associated with enhanced susceptibility to apoptosis due to activation of pro-apoptosis genes, neurite retraction (synaptic disconnection), and impaired transport of mitochondria to cell processes where they are likely required for synaptic function. In contrast, hypoxia-type injury causes neuronal loss with proliferation of neurites (sprouting), impaired mitochondrial function, and reduced expression of molecules required to form and maintain synaptic connections. Since similar abnormalities occur in AD, both oxidative stress and hypoxic injury can contribute to AD neurodegeneration.

Alzheimer Disease↗

Oxygen free radical injury is sufficient to cause some Alzheimer-type molecular abnormalities in human CNS neuronal cells.

Cell loss and neuritic/cytoskeletal lesions represent two of the major categories of dementia-associated structural abnormalities in Alzheimer's disease (AD). Cell loss is ultimately mediated by apoptosis and mitochondrial DNA damage due to enhanced sensitivity to oxidative stress, but the mechanism responsible for the neuritic/cytoskeletal lesions including the abnormal proliferation of cortical neurites is not known. This study examines the potential role of oxygen free radical injury as a factor contributing to both cell death and neuritic sprouting cascades in AD. PNET2 human neuronal cells were treated with H2O2 (8 micro M to 88 micro M) for 24 hours and then analyzed for viability, DNA damage, and pro-apoptosis, survival, and sprouting gene expression and signaling. H2O2-treatment resulted in dose-dependent increases in cell death due to genomic and mitochondrial DNA damage associated with increased levels of 8-OHdG and the p53 and CD95 pro-apoptosis genes, reduced levels of the Bcl-2 survival gene, activation of JNK and p38 stress kinases, and inhibition of PI3 kinase survival signaling. However, the H2O2-treated cells also manifested increased expression of growth and sprouting molecules, including GAP-43, nitric oxide synthase 3, neuronal thread protein (NTP; approximately 17 kD and approximately 21 kD forms), proliferating cell nuclear antigen, and phospho-Erk MAPK, and normal levels of the AD-associated approximately 41 kD NTP species, cyclin dependent kinase 5 (cdk-5), and phospho-tau. In addition, the H2O2-treated cells had increased levels of p25, the catalytically active and stable cleavage product of p35, which regulates cdk-5 activity. Previous studies demonstrated p25 accumulation in AD brains and p25-induced hyperphosphorylation of tau and neuronal apoptosis. The findings herein suggest that oxygen free radical injury in human CNS neuronal cells is sufficient to cause some but not all of the pro-death and pro-sprouting molecular abnormalities that occur in AD.

Journal Article↗

The use of diffusion tensor imaging in quantifying the effect of dexamethasone on brain tumours.

The role of dexamethasone in the treatment of patients with brain tumours remains poorly understood. In this study the self-diffusion parameters of extracellular water within primary intracranial tumours and peritumoural tissue, and their response to dexamethasone, have been measured using MR diffusion tensor imaging. Maps of the mean diffusivity and two measures of diffusion anisotropy were obtained from six patients before, and typically 48-72h after, commencing dexamethasone treatment. A significant decrease in of either tumour (p < 0.02) or oedematous brain (p < 0.04) was observed in three patients. No significant changes were noted in either of the two calculated diffusion anisotropy indices before and after steroid treatment in any of the six patients.

Adult↗

1H spectroscopic imaging of acute head injury--evidence of diffuse axonal injury.

Using single slice two-dimensional spectroscopic imaging (SI), nine acute head injury patients and six controls have been successfully scanned. The problems presented by the need for ITU monitoring of these patients during MR scanning was overcome using MR compatible monitoring equipment. In previous studies of head injury which used proton spectroscopy, single voxel localisation procedures have meant that the spatial extent of the spectral data has been limited. With spectral data from a whole axial slice, we have been able to identify NAA abnormalities in regions remote to any T2 visible lesions. This suggests that SI (of NAA in particular) will be useful for the diagnosis of diffuse axonal injury.

Adult↗

A macrolactam inhibitor of T helper type 1 and T helper type 2 cytokine biosynthesis for topical treatment of inflammatory skin diseases.

T lymphocytes play a critical part in inflammatory skin diseases but are targeted by available therapies that have only partial efficacy, significant side-effects, or both. Because psoriasis, atopic dermatitis, and allergic contact hypersensitivity are associated with T helper type 1 (Th1), T helper type 2 (Th2), or mixed Th1-Th2 cell subsets and cytokine types, respectively, there is a need for a better broad-based inhibitor. The macrolactam ascomycin analog, ABT-281, was found to inhibit potently T cell function across species and to inhibit expression of multiple cytokines in human peripheral blood leukocytes which have been found in human skin disease cells and tissues. These included immunoregulatory Th1 (interleukin-2 and interferon-gamma) and Th2 (interleukin-4 and interleukin-5) cytokines. ABT-281 was shown to have potent topical activity (ED50 = 0.6% in acetone/olive oil) in a stringent swine model of allergic contact hypersensitivity, but its potency was markedly reduced compared with ascomycin when administered systemically due to more rapid clearance. Topical application of 3% ABT-281 in acetone/olive oil over 25% of the body surface in swine resulted in undetectable blood levels. Compared with a wide potency range of topical corticosteroids in clinical formulations, 0.3% and 1% ABT-281 ointments profoundly inhibited dinitrochlorobenzene-induced contact hypersensitivity in the pig by 78% and 90%, respectively, whereas super-potent steroids such as clobetasol propionate only inhibited in the 50% range and mild to moderate potency steroids such as fluocinolone acetonide were inactive. The potent topical activity of ABT-281 in swine, its superior efficacy, its rapid systemic clearance following uptake into the bloodstream, and its ability to inhibit cytokine biosynthesis of both Th1 and Th2 cell subsets, suggests that it will have a broad therapeutic value in inflammatory skin diseases, including psoriasis, atopic dermatitis, and allergic contact dermatitis.

Administration, Topical↗

Accuracy of a miniature intracranial pressure monitor, its function during magnetic resonance scanning, and assessment of image artifact generation.

OBJECTIVE: We examined the accuracy and repeatability of an intracranial pressure (ICP) monitor (Codman MicroSensor; Johnson & Johnson Professional, Inc., Raynham, MA) in a nonmagnetic environment and during magnetic resonance imaging (MRI). The resulting image artifact generation was calculated. ICP monitoring is essential in management of severe head injury, but few ICP monitoring devices are compatible with use in an MRI scanner. The use of MRI to assess head injury is increasing, and developing safe methods of continuously monitoring ICP may improve patient care. METHODS: A water manometer was used as the standard for comparison. We assessed pressure readings from the ICP monitor in a nonmagnetic environment using a standard and a long connector cable between the pressure transducer and display unit. This long cable permitted testing during MRI sequences because the display unit could be distanced from the magnet. Accuracy was determined during T2-weighted imaging, proton spectroscopy, and diffusion-weighted imaging, and artifact generation was assessed. RESULTS: We found a high degree of accuracy for repeated measurements over a clinical pressure range using both standard and long connector cables outside the MRI room. During MRI scanning, the ICP monitor was accurate during T2 and proton spectroscopy sequences. Accuracy during diffusion-weighted imaging, however, was clinically unacceptable. This ICP monitor creates a reduction in signal-to-noise ratio in the received signal during T2-weighted imaging and proton spectroscopic imaging, with the obtained images still radiologically interpretable. CONCLUSION: The Codman ICP monitor is sufficiently accurate and free of artifact generation to be used during most clinical MRI applications. This could enhance patient monitoring and safety.

Artifacts↗

Production and evaluation of guidelines for the management of inflammatory bowel disease: the Leicester experience.

Consensus guidelines for the management of patients with inflammatory bowel disease were produced by gastroenterologists, gastrointestinal surgeons and a cross-section of general practitioners (GPs) from Leicestershire in order to develop a seamless pattern of care with a common approach to diagnosis and treatment. It was hoped that the guidelines would encourage a movement towards care in the community for many patients with stable disease and so speed up new consultation rates. The study then assessed the impact of these guidelines on the referral letters of GPs to hospital consultants, the prediction of disease and adherence to them on re-referring patients after discharge. The guidelines were distributed to all 487 GPs in the Leicester Health Authority area and the gastroenterology teams within the hospitals. The value of the guidelines was assessed by an audit of referral letters, the length of time from referral letter to out-patient appointment, both before and after the launch of the guidelines, adherence to the guidelines on re-referral, and monitoring the outcome of the discharged patients. Whilst the guidelines may have helped GPs to manage stable patients in the community, the content of referral letters and the diagnostic abilities of GPs were not seen to improve since the launch of the guidelines. However, only 5% of stable patients who were discharged from one clinic were re-referred for inflammatory bowel disease.

Attitude↗

Diffusion anisotropy measurements in ischaemic stroke of the human brain.

Magnetic resonance diffusion imaging was performed on 12 patients presenting with symptoms of acute ischaemic stroke (1-6 days post-ictus). Apparent diffusion coefficient (ADC) and diffusion anisotropy measurements were obtained from ischaemic and contralateral normal regions. ADC measurements were decreased by around 40% in ischaemic regions, indicated by an average stroke to normal ratio of 0.56 +/- 0.04 (p < 0.0001). The measured anisotropy was shown to be significantly increased in ischaemic regions, using both standard deviation and volume ratio anisotropy indices, which gave stroke to normal ratios of 1.78 +/- 0.27 (p = 0.003) and 0.87 +/- 0.05 (p = 0.005) respectively. The effects of gradient interactions, image registration, noise contamination and rotational variance and their implications for the results obtained in this study are discussed.

Acute Disease↗

Observer variability in the measurement of the size of intracranial aneurysms using power TCD.

This study assessed the observer variability for measurement of intracranial aneurysmal size visualized on color "power" Transcranial Doppler Ultrasound (TCD). Patients with recent subarachnoid hemorrhage underwent color "power" TCD blind to angiography. Identified aneurysms were measured from the frozen image (in real time or from video tape) using the trackball function. Two observers measured the maximum (systolic) and minimum (end diastolic) area of each aneurysm, and an adjacent reference artery. Each observer was blind to the other's results. Interobserver variability was assessed using the Bland and Altman technique. Thirty-nine aneurysms were identified in 32 patients in 10 months. The maximum cross-sectional area of the aneurysm was 38:41 mm2 (observer 1:observer 2), and the mean difference was -3 mm2 (95% confidence interval [CI] of the difference -5.4-1.46 mm2). The maximum cross-sectional area of the reference artery was 26:28 mm2 (observer 1:observer 2), and the mean difference was -2 mm2 (95% CI -5.7-1.2 mm2). Neither difference was significant. Intraobserver reliability also was good. The measurement of intracranial aneurysm and artery size with power TCD is reliable sufficiently for use in longitudinal studies of changes in aneurysm size.

Adult↗