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Biomedical subjects

K Greenwood

Publications and source records attributed to K Greenwood.

17 recordsLinked to original sources

Nematode neuropeptide receptors and their development as anthelmintic screens.

This review addresses the potential use of neuropeptide receptors for the discovery of anthelmintic agents, and particularly for the identification of non-peptide ligands. It outlines which nematode neuropeptides are known and have been characterized, the published information on drug discovery around these targets, information about existing high- and low-throughput screening systems and finally the likely safety of neuropeptide mimetics.

Animals↗

The high-level mobility assessment tool (HiMAT) for traumatic brain injury. Part 1: Item generation.

PRIMARY OBJECTIVE: To generate a comprehensive list of items for a scale suitable for assessing high-level mobility in people with traumatic brain injury (TBI). RESEARCH DESIGN: High-level mobility items were generated following a critical evaluation of existing adult and paediatric mobility scales and by surveying expert clinicians for opinions about items appropriate for inclusion on a high-level mobility scale. MAIN OUTCOMES AND RESULTS: The critical evaluation identified 18 different items from 31 mobility scales. These included nine walking items in addition to higher level activities such as stair use, running, jumping and hopping. Expert clinicians generated 157 items that were collated and condensed to 88 items for ranking on a questionnaire. Fifteen items on the questionnaire were rated as very important by 80% of the expert clinicians. These included walking forwards, walking on slopes and different surfaces, changing direction, walking long distances and stair use. Running items included forwards, backwards, on slopes and over different surfaces, changing direction, stopping and starting as well as running long distances. Balancing in single limb stance was also included. CONCLUSION: The final list comprised walking, running, hopping, skipping, jumping and balance items. This initial version of the HiMAT has face and content validity although requires further testing to investigate whether it is uni-dimensional and valid for people with TBI.

Activities of Daily Living↗

Nursing recruitment. First impressions.

Preparations for developing a standard induction programme across 15 trusts for overseas nurses in Manchester revealed a wide variation in the terms and conditions on which nurses were being employed. Some nurses were not paid at all, others were paid as auxiliaries and some were paid as staff nurses. Some induction programmes in operation lasted a couple of days, others three or four weeks. There should be a minimum two-week induction period. The standard programme developed for the area recommends that overseas nurses should be paid a minimum of 12,000 Pounds.

Foreign Professional Personnel↗

Structural abnormalities in frontal, temporal, and limbic regions and interconnecting white matter tracts in schizophrenic patients with prominent negative symptoms.

OBJECTIVE: Imaging studies of schizophrenia have repeatedly demonstrated global abnormalities of cerebral and ventricular volumes. However, pathological changes at more local levels of brain organization have not yet been so clearly characterized because of the few brain regions of interest heretofore included in morphometric analyses as well as heterogeneity of patient samples. METHOD: Dual echo magnetic resonance imaging (MRI) data were acquired at 1.5 T from 27 right-handed patients who met DSM-IV criteria for schizophrenia with enduring negative symptoms and from 27 healthy comparison subjects. Between-group differences in gray and white matter volume were estimated at each intracerebral voxel after registration of the images in standard space. The relationship between clinical symptom scores and brain structure was also examined within the patient group. Spatial statistics and permutation tests were used for inference. RESULTS: Significant deficits of gray matter volume in the patient group were found at three main locations: 1) the left superior temporal gyrus and insular cortex, 2) the left medial temporal lobe (including the parahippocampal gyrus and hippocampus), and 3) the anterior cingulate and medial frontal gyri. The volume of these three regions combined was 14% lower in the patients relative to the comparison subjects. White matter deficits were found in similar locations in the left temporal lobe and extended into the left frontal lobe. The patient group showed a relative excess of gray matter volume in the basal ganglia. Within the patient group, basal ganglia gray matter volume was positively correlated with positive symptom scores. CONCLUSIONS: Anatomical abnormalities in these schizophrenic patients with marked negative symptoms were most evident in left hemispheric neocortical and limbic regions and related white matter tracts. These data are compatible with models that depict schizophrenia as a supraregional disorder of multiple, distributed brain regions and the axonal connections between them.

Adult↗

Branched chain amino acids induce apoptosis in neural cells without mitochondrial membrane depolarization or cytochrome c release: implications for neurological impairment associated with maple syrup urine disease.

Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by a deficiency in branched chain alpha-keto acid dehydrogenase that can result in neurodegenerative sequelae in human infants. In the present study, increased concentrations of MSUD metabolites, in particular alpha-keto isocaproic acid, specifically induced apoptosis in glial and neuronal cells in culture. Apoptosis was associated with a reduction in cell respiration but without impairment of respiratory chain function, without early changes in mitochondrial membrane potential and without cytochrome c release into the cytosol. Significantly, alpha-keto isocaproic acid also triggered neuronal apoptosis in vivo after intracerebral injection into the developing rat brain. These findings suggest that MSUD neurodegeneration may result, at least in part, from an accumulation of branched chain amino acids and their alpha-keto acid derivatives that trigger apoptosis through a cytochrome c-independent pathway.

Amino Acids, Branched-Chain↗

Fas/CD95/APO-1 can function as a death receptor for neuronal cells in vitro and in vivo and is upregulated following cerebral hypoxic-ischemic injury to the developing rat brain.

Fas/CD95/Apo-1 is a cell surface receptor that transduces apoptotic death signals following activation and has been implicated in triggering apoptosis in infected or damaged cells in disease states. Apoptosis is a major mechanism of neuronal loss following hypoxic-ischemic injury to the developing brain, although the role of Fas in this process has not been studied in detail. In the present study, we have investigated the expression and function of Fas in neuronal cells in vitro and in vivo. Fas was found to be expressed in the 14 day old rat brain, with strongest expression in the cortex, hippocampus and cerebellum. Cross-linking of Fas induced neuronal apoptosis both in neuronal PC12 cells in culture and following intracerebral injection in vivo, indicating that neuronal Fas was functional as a death receptor. This death was shown to be caspase dependent in primary neuronal cultures and was blocked by the selective caspase 8 inhibitor IETD. Finally, cerebral hypoxia-ischemia resulted in a strong lateralised upregulation of Fas in the hippocampus, that peaked six to twelve hours after the insult and was greater on the side of injury. These results suggest that Fas may be involved in neuronal apoptosis following hypoxic-ischemic injury to the developing brain.

Animals↗

Magnesium sulfate treatment after transient hypoxia-ischemia in the newborn piglet does not protect against cerebral damage.

Transient perinatal hypoxia-ischemia (HI) can lead to delayed cerebral damage beginning 8-24 h after resuscitation. Cerebroprotective therapies applied soon after HI may thus reduce the severity of brain injury. We have previously shown that MgSO4 administration to newborn piglets after HI fails to prevent the delayed global impairment in cerebral energy metabolism characteristic of severe brain damage. However, high extracellular concentrations of magnesium ions have been found to prevent specific excitotoxic neural cell death in vivo and in vitro. This study therefore examined the hypothesis that MgSO4 administration after HI reduces damage in some regions of the brain even though global energy metabolism is unaffected. Twelve newborn piglets were subjected to global cerebral HI by transient occlusion of both common carotid arteries and reduction of the inspired oxygen fraction to 0.12 until cerebral high-energy phosphates, measured by magnetic resonance spectroscopy, were significantly depleted. Subjects were randomly assigned to two groups of six: the first received MgSO4 (three doses, 400 mg/kg 1 h after resuscitation and 200 mg/kg at 12 and 24 h), and the second received placebo infusions. At 48 h after the start of the experiment, the piglets were killed and their brains were perfused, fixed, and embedded in paraffin wax. Five-micrometer sections were stained with hematoxylin and eosin to allow semiquantitative analysis of the severity and extent of injury to the hippocampus, cerebellum, cerebral cortex, caudate nucleus, thalamus, and striatum and the white matter tracts. There was no difference in the severity of tissue damage between the MgSO4-treated group and the placebo-treated animals in any brain region.

Animals↗

A modified fuzzy clustering algorithm for operator independent brain tissue classification of dual echo MR images.

Methods for brain tissue classification or segmentation of structural magnetic resonance imaging (MRI) data should ideally be independent of human operators for reasons of reliability and tractability. An algorithm is described for fully automated segmentation of dual echo, fast spin-echo MRI data. The method is used to assign fuzzy-membership values for each of four tissue classes (gray matter, white matter, cerebrospinal fluid and dura) to each voxel based on partition of a two dimensional feature space. Fuzzy clustering is modified for this application in two ways. First, a two component normal mixture model is initially fitted to the thresholded feature space to identify exemplary gray and white matter voxels. These exemplary data protect subsequently estimated cluster means against the tendency of unmodified fuzzy clustering to equalize the number of voxels in each class. Second, fuzzy clustering is implemented in a moving window scheme that accommodates reduced image contrast at the axial extremes of the transmitting/receiving coil. MRI data acquired from 5 normal volunteers were used to identify stable values for three arbitrary parameters of the algorithm: feature space threshold, relative weight of exemplary gray and white matter voxels, and moving window size. The modified algorithm incorporating these parameter values was then used to classify data from simulated images of the brain, validating the use of fuzzy-membership values as estimates of partial volume. Gray:white matter ratios were estimated from 20 twenty normal volunteers (mean age 32.8 years). Processing time for each three-dimensional image was approximately 30 min on a 170 MHz workstation. Mean cerebral gray and white matter volumes estimated from these automatically segmented images were very similar to comparable results previously obtained by operator dependent methods, but without their inherent unreliability.

Adult↗

Poly(ADP ribose) polymerase cleavage precedes neuronal death in the hippocampus and cerebellum following injury to the developing rat forebrain.

Transient unilateral forebrain hypoxia-ischaemia (HI) in 14-day-old rats produces infarction and delayed neuronal death in the frontal cortex. Cell death can also be observed in regions distant from the primary injury, a phenomenon known as diaschisis. While apoptosis is involved in selective neuronal death, its role in infarction and diaschisis remains poorly understood. Here, we have investigated the proteolytic cleavage of poly(ADP ribose) polymerase (PARP) and the occurrence of apoptosis in the hippocampus and the cerebellum following either HI or traumatic brain injury. We demonstrate that: (i) in vitro, PARP is cleaved during apoptosis but not necrosis in cultured neuronal (N1E) cells and Swiss 3T3 fibroblasts; (ii) following HI, apoptotic cells can be detected by 4 h after injury in the hippocampus; (iii) in the ipsilateral hippocampus the appearance of cells with apoptotic morphology is preceded by a dramatic increase in PARP cleavage in the same region, starting immediately following HI and persisting for 24 h; (iv) HI also induces apoptosis in the cerebellum and, as in the hippocampus, the appearance of cells with apoptotic morphology is preceded by PARP cleavage that is greater on the side ipsilateral to forebrain injury; and (v) similarly, traumatic brain injury to the forebrain leads to PARP cleavage and apoptosis in the cerebellum. We conclude that HI injury or traumatic injury to the developing rat forebrain leads to PARP cleavage in directly affected areas and in sites distant from the primary injury that precedes the appearance of cells with apoptotic morphology. Our results are consistent with a role for apoptotic cell death in infarction and in diaschisis resulting from forebrain injury to the developing brain.

3T3 Cells↗

Prediction of length of hospital stay following stroke.

The aim of this study was to investigate the potential of using an assessment of initial physical disability post stroke to predict length of hospital stay (LOS). A series of 106 patients with a primary diagnosis of stroke, admitted consecutively to St Vincent's Hospital Rehabilitation Unit over a 2-year period, was assessed at 2 weeks post stroke using the Mobility Scale for Acute Stroke (MSAS). This scale assesses the level of assistance required for a patient to perform five mobility tasks: bridging, sitting from supine, sitting, sitting to standing, and walking. A model utilizing MSAS data explained 69% of the variation in LOS. The results of this study may assist in developing resource utilization models in stroke rehabilitation.

Activities of Daily Living↗

Methodological considerations in nicotine research: the use of "denicotinised" cigarettes as the control condition in smoking studies.

In this study, we report on the comparability of the subjective experience and smoking style elicited by two commercially available cigarettes which differ in nicotine levels, one containing a 'regular' delivery of 0.7 mg and the other containing minimal (0.1 mg) nicotine. Our findings suggest subtle differences in the smoking of these two cigarettes, with the 'denicotinised' cigarette being smoked for longer and with more puffs taken. While these subtle differences have little significance for studies concerned with the effects of nicotine on cognitive performance measures, they are certainly important for studies concerned with the role of nicotine in maintaining smoking behaviour.

Adult↗

Performance effects on the voices of 10 choral tenors: acoustic and perceptual findings.

Trained choral tenors performed a series of vocal tasks before and after a "live" performance. Acoustic (perturbation, harmonic-to-noise ratio, pitch and amplitude ranges) and perceptual analyses (auditory and proprioceptive/kinesthetic) were undertaken to detect changes from pre- to postperformance. Individuality of response to the performance was revealed, with the majority of subjects showing vocal deterioration after performance. The most sensitive vocal tasks were the comfortably pitched notes, high soft notes, and the bottom notes in scale singing. The most sensitive acoustic measure in detecting change from pre- to postperformance was harmonic-to-noise ratio. In contrast to the demonstrated acoustic changes, no significant differences in perceptual ratings were evident after the performance. Perceptual ratings did not reflect the acoustic analysis results. The present study highlights the need to establish further normative data for the singing voice and to consider individual differences in vocal characteristics in future studies of the singing voice.

Adult↗

Australian workers with back injury: a statistical overview.

This paper reviews international and Australian data concerning the occurrence of back injuries amongst the labour force. Analyses of Australian Bureau of Statistics data for the period 1977 to 1986 revealed substantial differences between Australian states in their rates of back injury claims for work injuries, with a decline in rates over the ten years surveyed. Analyses of WorkCare data from the State of Victoria in Australia revealed that claimants with back injury claims of greater than 12 months standing were very costly. A total of 8,633 claimants accounted for 68.7% of all payments for back injury ($362 million out of a total of $527 million) when these claimants represented only 10.7% of all back injury claimants for the period September 1985 to May 1989. Substantial variations were found in claim rates across occupations and age levels. An almost linear (r = 0.98) association was found between age and proportion of long term claimants at each age level. It is suggested that these data could be used to identify 'at risk' groupings with a view to the implementation of preventive measures.

Adolescent↗

Bilateral arytenoid cartilage lateralization for laryngeal paralysis in the dog.

Bilateral arytenoid cartilage lateralization was used successfully to treat 3 dogs with bilateral laryngeal paralysis. In our hands, this techniques was more effective than unilateral arytenoid cartilage lateralization in resolving the signs of laryngeal paralysis and in avoiding the complications that may follow partial laryngectomy.

Animals↗

Reversal of the anti-ovulatory action of stress in rats by prior administration of naloxone hydrochloride.

Immature, 32-day-old rats were treated with PMSG. Stress consisting of 180 min immobilization administered during the period of the preovulatory LH surge resulted in the blockage of ovulation. The anti-ovulatory action of stress was effectively antagonized by the administration of naloxone hydrochloride shortly before the application of the stress, suggesting that the ovulation block by stress is mediated by endogenous opioids known to be elevated during stress. Blockage of ovulation by 180 min immobilization stress occurred only in rats from one of the two laboratory strains tested, suggesting that stress resistance is, at least in part, genetically determined.

Animals↗

Persistence of rat nocturnal feeding and drinking during diurnal presentation of palatable diet.

Male laboratory rats were fed a highly palatable diet during the light phase of a 12:12 LD cycle. Nocturnality of feeding was reduced from approximately 77% of the total daily intake to 56%. Increase in diurnal feeding was attributable to the ingestion of a large meal at the beginning of the L phase. Reduction of nocturnal feeding was attributable to decreased ingestion in the first 3 hr of the D phase. Outside these times the daily feeding pattern was unmodified. These findings do not represent a reversal of the feeding rhythm as previously reported, but a modification which is not consistent with interpretation as a phase-shift. Throughout the testing period total daily food intake remained unchanged and body weight was defended despite the increase in calories ingested. Daily drinking patterns and total daily water intake were not significantly altered by the experimental manipulation.

Animals↗