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Biomedical subjects

P Walker

Publications and source records attributed to P Walker.

At least 55 records · Page 3Linked to original sources
PubMed1999

Expression of the novel galanin receptor subtype GALR2 in the adult rat CNS: distinct distribution from GALR1.

Recent molecular cloning studies by our laboratory and others have identified the existence of a novel rat galanin receptor subtype, GALR2. In the present study, we examined the regional and cellular distribution of GALR2 mRNA in the rat central nervous system (CNS) by in situ hybridization. For comparative purposes, adjacent sections were probed for GALR1 mRNA expression. Our findings indicate that dorsal root ganglia express by far the highest levels of GALR2 mRNA in the rat CNS. Hybridization signal is mainly concentrated over small and intermediate primary sensory neurons. In spinal cord, the large alpha motoneurons of the ventral horn are moderately labeled and several small, but less intensely labeled, cells are scattered throughout the gray matter. In brain sections, the highest levels of GALR2 mRNA are detected in granule cells of the dentate gyrus, in the mammillary nuclei, and in the cerebellar cortex. Moderate levels of GALR2 mRNA are observed in the olfactory bulb, olfactory tubercle, piriform and retrospinal cortices, hypothalamus (namely the preoptic area, arcuate nucleus, and dorsal hypothalamic area), substantia nigra pars compacta, and sensory trigeminal nucleus. Moderate to weak hybridization signal is also present in several other hypothalamic nuclei, specific layers of the neocortex, periaqueductal gray, and several nuclei within the pons and medulla, including locus coeruleus, lateral parabrachial, motor trigeminal, pontine reticular, hypoglossal, vestibular complex, ambiguus, and facial and lateral reticular nuclei. This novel pattern of GALR2 distribution within the rat CNS differs considerably from that of GALR1, suggesting that specific physiologic effects of galanin may be ascribed to the GALR2 galanin receptor subtype.

Age Factors↗
PubMed1999

Immunization through dermal delivery of protein-encoding DNA: a role for migratory dendritic cells.

The early mechanisms by which DNA-dependent immunization occurs remain poorly understood. We determined whether intradermal injection of a cytomegalovirus (CMV) promoter-driven plasmid encoding hen egg lysozyme (pCMV:HEL) induced sensitization against the encoded protein, and whether cutaneous dendritic cells (DC) were involved in this sensitization. Both humoral and cellular responses to HEL were observed. DC that migrated from skin explant culture 3 days after injection of pCMV:HEL DNA contained mRNA encoding HEL. They induced a 3.5-7-fold increase in [3H]thymidine incorporation by HEL protein-primed CD4+ T cells compared to that induced by DC from mice injected with control plasmid. DC emigrating from skin explants recovered from pCMV:HEL injected mice also sensitized naive mice after adoptive transfer and induced the generation of CTL. Thus following DNA delivery within the dermis, DC can induce primary and secondary immune responses.

Animals↗
PubMed1999

The use of intermittent subcutaneous injections of oxycodone for opioid rotation in patients with cancer pain.

Oxycodone is a strong opioid that has been available for at least 70 years. At present, commercially prepared parenteral oxycodone is only available in Finland. We report in this paper our experience of administering oxycodone s.c. From 21 October 1996 to 31 July 1998, 63 advanced cancer patients received intermittent s.c. injections of oxycodone via the Edmonton Injector, a simple, low-cost mechanical device. Local tolerance and systemic toxicity were followed prospectively. Only 2 patients developed s.c. injection site intolerance, and in both cases doses of 50 mg/ml or more were being administered. Most of the patients in this study were rotated to oxycodone because of opioid toxicity, and in 34% of those patients their delirium subsided. A subgroup of 19 patients who underwent rotation to oxycodone SC from morphine and hydromorphone were studied for equivalent analgesia with oxycodone. We found a ratio (mean +/- SD) of 1.2+/-0.4 for morphine s.c. to oxycodone s.c. and a mean ratio of 0.5+/-0.4 for hydromorphone s.c. to oxycodone s.c. When hydromorphone s.c. was converted to a morphine s.c. equivalent dose and the results for these patients were added to those for the morphine s.c. group, the mean and median overall ratios of morphine s.c. equivalent dose to oxycodone were 1.9+/-1.5 and 1.4, respectively. The cost of the oxycodone s.c. was also evaluated and was found to be comparable to that of morphine s.c. and lower than that of hydromorphone s.c. We conclude that s.c. oxycodone can be an effective, safe and inexpensive alternative opioid agonist.

Adult↗
PubMed1999

The receptor for the orexigenic peptide melanin-concentrating hormone is a G-protein-coupled receptor.

Gene-knockout studies of melanin-concentrating hormone (MCH) and its effect on feeding and energy balance have firmly established MCH as an orexigenic (appetite-stimulating) peptide hormone. Here we identify MCH as the ligand for the orphan receptor SLC-1. The rat SLC-1 is activated by nanomolar concentrations of MCH and is coupled to the G protein G alpha i/o. The pattern of SLC-1 messenger RNA expression coincides with the distribution of MCH-containing nerve terminals and is consistent with the known central effects of MCH. Our identification of an MCH receptor could have implications for the development of new anti-obesity therapies.

Animals↗
PubMed1999

Cerebral metabolism after transient ischemic attack. A 1H MR spectroscopy study.

Metabolic changes induced by cerebral infarction or by stenosis and occlusion of the internal carotid artery have been previously described in 1H Magnetic Resonance Spectroscopy (1H MRS). These changes are essentially characterized by decreased N-acetyl-aspartate (NAA) and increased lactate concentration. Little is known about the metabolic changes observed in the three days following a transient ischemic attack (TIA), in the absence of stenosis or occlusion of the internal carotid artery, and without visible infarction on Magnetic Resonance Imaging (MRI). We studied five patients with a TIA lasting between 30 min and 3 h, affecting the sensory and motor functions of the brachio-facial territory with or without aphasia. A Computerized Tomography Scan (CT-scan), an electro-encephalogram, cervical Doppler ultrasound and MRI with proton magnetic resonance spectroscopy were performed on the affected cerebral area and on the normal contralateral homologous cerebral area within three days of the onset of TIA. None of the five patients had stenosis or occlusion of the internal carotid artery on Doppler ultrasound, or cerebral infarction on MRI. From 1H MRS ratio measurements, we did not observe any significant changes in the NAA/Creatine ratio. However, a rise in Lactate/Creatine ratio was observed in the symptomatic non-infarcted area compared with the normal cerebral tissue. During the first three days following a transient ischemic attack, there is an increase in lactate production. This change may reflect transient local hypoperfusion which could be long enough to stimulate lactate production, but short enough not to induce infarction. This region could be at risk from infarction in the long term.

Aged↗
PubMed1999

Depolarising the 'broadened' and 'back-to-basics' relief models.

Prompted by the calls in recent years to link relief practice to peace-building, development, or both, several conferences and papers have recently mounted a strong critique, seeing these 'broadenings' of relief as 'eroding' or 'corrupting' core humanitarian principles and playing into neo-isolationist agendas to slash humanitarianism. This paper argues that whereas these critiques have important goals in mind when they encourage a concentration on the basics of relief, there has been a loss of subtlety in the ensuing debate. Considering each element of the debate in turn, the paper argues that there is more common ground between 'new' and 'old', 'broadened' and 'basics' relief than at first appears. In concluding, it is argued that further research on key questions, and an openness to hear all perspectives will get us further than entrenched positions and rallying cries.

Altruism↗
PubMed1999

The object-based representation of partially occluded surfaces in short-term visual memory: evidence from image combination.

Distinct short-term and longer term visual representations of form allow people to combine mental images of separately presented pictures in order to identify a novel object (see, e.g., Brandimonte, Hitch, & Bishop, 1992; Hitch, Brandimonte, & Walker, 1995; Walker, Hitch, Dewhurst, Whiteley, & Brandimonte, 1997). The present study focuses on the short-term representation and asks whether it describes the 2-D features in a picture or the depicted surfaces in 3-D space (see Nakayama, He, & Shimojo, 1995). To-be-combined figures were sometimes partially occluded by irrelevant forms, and it was determined whether image combination was contingent on the directly visible regions of the figures or on the perceptually completed figures. Results showed that image combination was not impeded by partial occlusion, though it was impeded if an occluder was removed from a picture and only the previously visible regions of the figure were presented. It is concluded that the short-term visual representation supporting image combination is not a pictorial code, but is an object-based description of completed surfaces in 3-D space.

Adolescent↗
PubMed1999

Subglottic haemangioma: controversies in management.

OBJECTIVE: To discuss treatment modalities for subglottic haemangioma (SGH). METHODOLOGY: Case report of two children definitively managed by different modalities. RESULTS: Management by CO2 laser vaporization in one child, and laser followed by interferon 2-alpha in the second child were both successful in controlling the SGH without the need for tracheostomy. CONCLUSION: The stepped-care approach at John Hunter Children's Hospital, Newcastle, New South Wales, is presented. Both laser surgery and interferon can help control SGH. Careful surveillance and interdisciplinary cooperation are essential to achieve a good outcome.

Antineoplastic Agents↗
PubMed1998

Cloning and evaluation of the role of rat GALR-2, a novel subtype of galanin receptor, in the control of pain perception.

We have identified a novel subtype of galanin receptor (GALR-2) in rat dorsal root ganglia and spinal cord. The open reading frame of GALR-2 is 1116 nucleotides long, encoding a protein of 372 amino acids with a theoretical molecular mass of 40.7 kD. Membranes prepared from stable pools of 293 cells expressing GALR-2, but not wild-type 293 cells, demonstrated high affinity galanin binding sites. Rat galanin and galanin-related peptides M40, C7, M15, and galanin effectively competed for binding; peptide C7 demonstrated a lower affinity for rGALR-2, and all these peptides were agonists at rGALR-2 when assessed on a microphysiometer. Studies on the expression of GALR-2 in various tissues by Northern and in situ hybridization analyses suggest a low abundance but wide distribution of GALR-2 mRNA, including several discrete areas in brain and spinal cord and a high abundance in the dorsal root ganglia.

Amino Acid Sequence↗
PubMed1998

Cloning and characterization of a cDNA encoding a novel subtype of rat thyrotropin-releasing hormone receptor.

A cDNA encoding a thyrotropin-releasing hormone (TRH) receptor expressed in the pituitary was previously cloned (De La Pena, P., Delgado, L. M., Del Camino, D., and Barros, F. (1992) Biochem. J. 284, 891-899; De La Pena, P., Delgado, L. M., Del Camino, D., and Barros, F. (1992) J. Biol. Chem. 267, 25703-25708; Duthie, S. M., Taylor, P. L., Anderson, J., Cook, J., and Eidne, K. A. (1993) Mol. Cell Endocrinol. 95, R11-R15). We now describe the isolation of a rat cDNA encoding a novel subtype of TRH receptor (termed TRHR2) displaying an overall homology of 50% to the pituitary TRH receptor. Introduction of TRHR2 cDNA in HEK-293 cells resulted in expression of high affinity TRH binding with a different pharmacological profile than the pituitary TRH receptor. De novo expressed receptors were functional and resulted in stimulation of calcium transient as assessed by fluorometric imaging plate reader analysis. The message for TRHR2 was exclusive to central nervous system tissues as judged by Northern blot analysis. Studies of the expression of TRHR-2 message by in situ hybridization revealed a pattern of expression remarkably distinct (present in spinothalamic tract, spinal cord dorsal horn) from that of the pituitary TRH receptor (present in hypothalamus, and ventral horn of the spinal cord, anterior pituitary). Therefore, we have identified a novel, pharmacologically distinct receptor for thyrotropin-releasing hormone that appears to be more restricted to the central nervous system particularly to the sensory neurons of spinothalamic tract and spinal cord dorsal horn, which may account for the sensory antinociceptive actions of TRH.

Amino Acid Sequence↗
PubMed1998

Antisense inhibition of striatal GABAA receptor proteins decreases GABA-stimulated chloride uptake and increases cocaine sensitivity in rats.

The functional status of striatal GABAA receptors appears to be inversely related to the magnitude of cocaine-induced behaviors. Exposure of striatum to antisense oligodeoxynucleotides (ASODNs) targeted to the mRNAs for the alpha 2 and the beta 3 subunits of the GABAA receptor should decrease expression of receptor proteins and therefore might be expected to increase cocaine sensitivity. ASODNs, scrambled ODNs or saline were injected into right lateral ventricle of rats and behavioral responses to cocaine were tested 18-20 h after treatment. Animals injected separately with alpha 2 or beta 3 ASODNs exhibited increased behavioral sensitivity to cocaine compared to rats injected with saline or scrambled ODNs including performing more 360 degrees turns to the left than to the right. There was significantly less GABA-stimulated Cl uptake in right striatum compared to left striatum of ASODN-treated rats with no significant difference between sides in control animals. Specific binding to benzodiazepine and convulsant sites on the GABAA receptor was not selectively altered by ASODN treatment. Combined alpha 2 beta 3 ASODN treatment did not affect either cocaine sensitivity or GABAA receptor function. There was no difference between the density of Nissl stained cells in the left and right edges of striatum in control or ASODN-treated rats indicating the absence of significant neurotoxic effects of the ASODN treatment. Injection of fluorescein-conjugated ASODNs indicated that ASODN is present in striatum at times during which behavioral and neurochemical indices of GABA receptor function are decreased. Thus, the functional status of GABAA receptors in striatum may be involved in determining cocaine sensitivity.

Analysis of Variance↗
PubMed1998

Baclofen, a treatment for chronic hiccup.

The efficacy of baclofen in the treatment of chronic hiccup is demonstrated in two cases. These cases highlight the present state of knowledge related to hiccup. This discussion focuses on the definition and classification of hiccup, etiologies, postulated theories to explain its function, the few studies performed to date, and non-pharmacologic and pharmacologic treatment. Baclofen appears to be the agent most efficacious in the treatment of chronic hiccup. Its commonest side effect is sedation; insomnia, dizziness, weakness, ataxia, and confusion also can occur. Following regular use, abrupt discontinuation can lead to withdrawal symptoms, such as seizure, and gradual discontinuation is recommended.

Aged↗
PubMed1998

Sleep apnoea related hypoxia is associated with cognitive disturbances in patients with tetraplegia.

Sleep disordered breathing is common in patients with tetraplegia. Nocturnal arterial hypoxemia and sleep fragmentation due to sleep apnoea may be associated with cognitive dysfunction. We therefore studied the influence of sleep disordered breathing on neuropsychological function in 37 representative tetraplegic patients (mean age 34 +/- 9.7 years). Thirty percent (11 of 37 patients) had clinically significant sleep disordered breathing, defined as apnoea plus hypopnoea index (AHI) greater than 15 per hour of sleep. Most apnoeas were obstructive in type. Seven patients (19%) desaturated to < 80% during the night. Neuropsychological variables were significantly correlated with measures of sleep hypoxia, but not with the AHI and the frequency of sleep arousals. The neuropsychological functions most affected by nocturnal desaturation were: verbal attention and concentration, immediate and short-term memory, cognitive flexibility, internal scanning and working memory. There appeared to be a weak association between the presence of severe sleep hypoxia and visual perception, attention and concentration but no association was found between sleep variables and depression scores. We concluded that sleep disordered breathing is common in patients with tetraplegia and may be accompanied with significant oxygen desaturation. The latter impairs daytime cognitive function in these patients, particularly attention, concentration, memory and learning skills. Cognitive disturbances resulting from sleep apnoea might adversely affect rehabilitation in patients with tetraplegia.

Adolescent↗
PubMed1998

Predischarge screening of very low birthweight infants by click evoked otoacoustic emissions.

OBJECTIVE: To evaluate the role of transient evoked otoacoustic emission (TEOAE) in screening very low birthweight (VLBW) neonatal intensive care unit (NICU) graduates for hearing loss in comparison with visual reinforcement orientation audiology (VROA) at 10 months. METHODOLOGY: The study population was all VLBW neonatal survivors discharged from a single regional NICU at John Hunter Childrens Hospital (JHCH), Newcastle, New South Wales, Australia, between April 1994 and March 1996. A TEOAE screen was performed prior to discharge and repeated if necessary until a pass was obtained in at least one ear. Infants were further screened by VROA at their local Australian Hearing Services (AHS) office at 10 months corrected age. Repeated TEOAE failures were referred directly for an ENT opinion. RESULTS: A total of 193 infants were eligible for enrolment during the study period. One hundred and forty-four (75%) received TEOAE testing. The median age of first screen was 36 weeks gestational age. Ninety-five (66%) of infants tested passed on a single screen. Of the remaining 49 infants, 26 passed on retesting (overall pass rate 84%). Twenty-three (16%) were deemed to have failed the TEOAE screen. Of the 121 infants who passed TEOAE, only 67 (55%) completed VROA. Two of these infants have a high frequency sensorineural loss and one of them has been aided. In the 23 who failed TEOAE, nine have subsequently had normal VROA, another, though not tested is clinically normal. three have hearing loss with middle ear disease and eight have confirmed sensorineural deafness, all aided. One infant has died and an infant with Down's syndrome has been adopted out of the area. It is of interest to note that the eight aided infants are all of less than 28 weeks gestation. If we restrict analysis to infants with completed VROA testing, the TEOAE has a 97% negative predictive value for sensorineural deafness and a 38% positive predictive value. CONCLUSIONS: This study has highlighted both the prevalence of hearing impairment in the very premature survivors and difficulties in compliance with a VROA based hearing screen. We see an advantage in directing resources towards an early screening test, such as TEOAE, that can be applied while the target population is still captive.

Audiometry, Evoked Response↗