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Biomedical subjects

D Walker

Publications and source records attributed to D Walker.

At least 163 records · Page 9Linked to original sources
PubMed1998

Efficacy of CI-1020, an endothelin-A receptor antagonist, in hypoxic pulmonary hypertension.

We previously showed that CI-1020, an endothelin (ET)-A-selective receptor antagonist, dose-dependently blocked acute hypoxic pulmonary hypertension (PH) in rats. In this study we show that CI-1020 can reverse existing PH and prevent progression of right ventricular hypertrophy (RVH) in rats exposed to chronic hypoxia. Male Sprague-Dawley rats were exposed to 20 days of hypoxia (10% O2) with CI-1020 treatment (20 or 40 mg/kg/day) starting on day 10. On day 20 of hypoxia, the rats were instrumented under anesthesia with a pulmonary artery cannula and allowed to recover to consciousness before measurement of mean pulmonary arterial pressure (MPAP). Blood samples were then collected for plasma ET-1 measurements, the rats killed, and their hearts dissected, dried, and weighed. RV/LV + septum ratio (g/g) was used as an index of RVH (RVHi). Normoxic rats and rats exposed to hypoxia for only 10 days were also evaluated as controls. Normoxic rats had MPAPs of 13 +/- 1 mm Hg, plasma ET-1 levels of 2.1 +/- 0.1 pg/ml, and an average RVHi of 0.29 +/- 0.03. Rats exposed to 10 or 20 days of hypoxia had MPAPs of 33 +/- 2 and 44 +/- 0 mm Hg, plasma ET-1 levels of 4.2 +/- 0.8 and 4.6 +/- 0.8 pg/ml, and average RVHis of 0.47 +/- 0.05 and 0.52 +/- 0.03, respectively. In comparison, rats treated with CI-1020 had MPAPs that were 37% (20 mg/kg/day) and 44% (40 mg/kg/day) lower than untreated 20-day hypoxic rats. Furthermore, rats dosed with 40 mg/kg/day of CI-1020 had MPAPs that were significantly lower (24%) than control 10-day hypoxic rats, indicating a significant reversal of PH. Along with this reversal in PH, their average RVHi was 23% lower (p < 0.05) relative to untreated 20-day hypoxic rats.

Animals↗
PubMed1998

Rickettsia honei sp. nov., the aetiological agent of Flinders Island spotted fever in Australia.

The name Rickettsia honei, strain RBT, has been proposed for a unique spotted fever group (SFG) agent which is pathogenic for humans. This agent has previously been compared to the other SFG agents and was shown to be distinct in protein structure by SDS-PAGE and by immunoblotting. Genetic comparisons of the 16S rRNA, rompA, gltA and the 17 kDa antigen genes with the other SFG rickettsiae confirmed the phylogenetic distance between R. honei and the previously described species. Genetically, Rickettsia honei is more closely related to the Thai tick typhus (TT-118) rickettsia than to any other member of the SFG. Indeed, it is proposed that TT-118 is a strain of R. honei which was previously isolated in Thailand. These results elucidate the presence of a unique SFG rickettsial species in Australasia.

Antigens, Bacterial↗
PubMed1998

Improving musculoskeletal clinical skills teaching. A regionwide audit and intervention study.

OBJECTIVE: To identify factors that influence medical students' perceptions of the quality of a clinical skills course; to apply these factors to the course at one hospital; to measure the effect of this change. DESIGN: Cross sectional questionnaire survey; application of identified factors; repeat questionnaire survey. SETTING: Three teaching hospitals and five district general hospitals in north east England. SUBJECTS: Third year medical students attending locomotor clinical skills courses in two consecutive years. MAIN OUTCOME MEASURES: Score awarded by students in five categories; numbers of patients seen by each student; comparisons with other clinical skills weeks. RESULTS: Response rates were 71 of 150 and 89 of 161. Factors associated with a high awarded score were: organisation of the course by a rheumatologist (p < 0.01); teaching from a rheumatologist (p < 0.01); higher number of patients seen (r = 0.76). Mean number of patients seen varied widely, from 7 per student at one hospital to 20.4 at another. Teaching hospitals scored poorly. In the second year, after making changes at one teaching hospital the mean total score improved (p < 0.01), and students saw more patients (p < 0.01). The ranking of this hospital rose from 6 to 1. The additional cost of the modified course was 640 pounds per student. CONCLUSIONS: The standard of teaching of locomotor clinical skills varies widely and can be improved by application of factors identified in this survey, although additional costs are incurred.

Clinical Competence↗
PubMed1998

A three-decade perspective on community and public psychiatry training in Oregon.

The public psychiatry training program at Oregon Health Sciences University, established in 1973, educates psychiatric residents to work in community mental health centers and state hospitals. The authors present a brief history of this program, which spans three decades, and describe recent developments in its operation, with special attention to financing, administrative structure, and educational elements. Several program graduates have chosen careers in public-sector work. The program is founded on the principle that just as dollars should follow patients in health care systems, so should residents in training follow patients. Administrative and fiscal arrangements must be flexible to support this mobility.

Career Choice↗
PubMed1998

Maternal, umbilical, and amniotic fluid concentrations of tryptophan and kynurenine after labor or cesarean section.

A major route of tryptophan metabolism is via the hepatic and cerebral synthesis of kynurenine, a substance subsequently used by astrocytes in the brain for the production of the neuroactive substances kynurenic acid and quinolinic acid. Both kynurenic and quinolinic acids have been implicated in modulating the activity of excitatory amino acid pathways in the brain, the former as a neuroprotectant because of its antagonist properties, and the latter as an excitotoxin because of its agonist actions, at NMDA receptors. We therefore determined the concentrations of tryptophan and kynurenine in maternal venous and umbilical cord blood, and in amniotic fluid, of infants after labor and vaginal delivery, and after delivery by cesarean section. Concentrations of tryptophan and kynurenine were significantly higher in umbilical vein plasma compared with maternal venous plasma. Tryptophan and kynurenine concentrations in umbilical vein plasma and amniotic fluid were significantly higher after labor, compared with samples obtained from infants of the same gestational age delivered by cesarean section. There was no umbilical vein-to-artery concentration difference for kynurenine in samples obtained after either labor or cesarean section, but there was a significant gradient for tryptophan in samples obtained after vaginal delivery, indicating increased transfer of this amino acid during labor. There was a significant correlation between umbilical vein tryptophan and kynurenine concentrations for both the labor and cesarean section groups, and plasma kynurenine concentrations were also significantly correlated with both umbilical vein cortisol concentrations and the duration of the second stage of labor in the vaginally delivered infants. These results suggest that the placental transfer of tryptophan and the fetal synthesis of kynurenine are increased during labor. These findings have implications for understanding the vulnerability of the infant brain to ischemic/hypoxic damage in the perinatal period. By analogy with the adult brain, the molar ratio of these substances is likely to determine the susceptibility of the brain to seizure and excitotoxic damage.

Adult↗
PubMed1998

Formative design of a virtual learning environment.

Current technology for 3D visualization, modeling and interaction allows the construction of attractive virtual environments for study of anatomy, surgery and other biomedical fields. The formative methodology for designing such environments is uncharted, but necessary before committing to large scale development. We present one such methodology undertaken during the design of a learning environment for biology for high school and middle school students. We expect to extend this design methodology to the development of environments for the teaching of medical subjects.

Animals↗
PubMed1998

Management of psychiatric symptoms in medically ill patients in the homecare setting.

Nurses with critical care knowledge and experience increasingly provide technologically advanced care to patients at home who often present comorbid psychiatric symptoms. Failure to accurately recognize and provide appropriate intervention can be devastating for patients because these symptoms can exacerbate the medical condition and may lead to mortality. The Biopsychosocial Model and the Transactional Model of Stress were presented as guides for nursing practice. Practice is directed at 1) understanding the patient's perception of events, 2) involving the caregiver(s) in the patient's recovery, and 3) enhancing the individual's adaptive coping efforts and resources. The article attempts to guide nurses in making decisions on when to consult and collaborate with an APPN to achieve desired patient outcomes.

Community Health Nursing↗
PubMed1997

Direct interaction of the calcium sensor protein synaptotagmin I with a cytoplasmic domain of the alpha1A subunit of the P/Q-type calcium channel.

Synaptotagmins are synaptic vesicle proteins containing two calcium-binding C2 domains which are involved in coupling calcium influx through voltage-gated channels to vesicle fusion and exocytosis of neurotransmitters. The interaction of synaptotagmins with native P/Q-type calcium channels was studied in solubilized synaptosomes from rat cerebellum. Antibodies against synaptotagmins I and II, but not IV co-immunoprecipitated [125I]omega-conotoxin MVIIC-labelled calcium channels. Direct interactions were studied between in vitro-translated [35S]synaptotagmin I and fusion proteins containing cytoplasmic loops of the alpha1A subunit (BI isoform). Gel overlay revealed the association of synaptotagmin I with a single region (residues 780-969) located in the intracellular loop connecting homologous domains II and III. Saturable calcium-independent binding occurred with equilibrium dissociation constants of 70 nM and 340 nM at 4 degrees C and pH 7.4, and association was blocked by addition of excess recombinant synaptotagmin I. Direct synaptotagmin binding to the pore-forming subunit of the P/Q-type channel may optimally locate the calcium-binding sites that initiate exocytosis within a zone of voltage-gated calcium entry.

Amino Acid Sequence↗
PubMed1997

Identification of brainstem neurons responding to hypoxia in fetal and newborn sheep.

Hypoxia causes a reversible decrease in the level of respiratory, oculomotor and postural muscle activity in fetal sheep, an effect not seen in newborn lambs. We have used Fos immunohistochemistry to identify neurons which are activated by hypoxia and which may mediate this motor inhibition in the fetus. Pregnant sheep of either 117 or 138 days gestation were made hypoxic by allowing them to breathe 8-9% O2 for 2 h. Compared to age-matched control fetuses, hypoxia caused a significant increase in Fos-immunoreactivity in several medullary nuclei including the nucleus tractus solitarius, lateral reticular nucleus and the rostral ventrolateral medulla and also in the lateral parabrachial nucleus, locus coeruleus and subcoeruleus region in the pons. Hypoxia in newborn lambs, 7-18 days old, resulted in Fos staining in the same medullary and pontine nuclei with the exception of the subcoeruleus region which was devoid of Fos-immunoreactivity. In newborn lambs in which the carotid sinus nerves had been sectioned bilaterally, Fos-immunoreactivity was increased in the nucleus tractus solitarius in the medulla and in the locus coeruleus, lateral parabrachial and Kölliker-Fuse nuclei in the pons when compared to intact control newborn lambs. When carotid sinus nerve denervated-lambs were subjected to hypoxia the pattern of Fos-ir was similar to the pattern seen in the denervated control lambs but in addition staining was present in the subcoeruleus. These results suggest that a specific set of pontine neurons are activated by low oxygen levels in the fetus but not in the newborn lamb in the presence of an intact innervation from the carotid sinus. We hypothesise that: (a) in the fetus hypoxia activates neurons in the region of the subcoeruleus and this causes cessation of breathing movements and muscle atonia; and (b) that after birth stimulation of the carotid chemoreceptors by hypoxia normally inhibits activation of these subcoeruleus neurons.

Aging↗
PubMed1997

Direct binding of G-protein betagamma complex to voltage-dependent calcium channels.

Voltage-dependent Ca2+ channels play a central role in controlling neurotransmitter release at the synapse. They can be inhibited by certain G-protein-coupled receptors, acting by a pathway intrinsic to the membrane. Here we show that this inhibition results from a direct interaction between the G-protein betagamma complex and the pore-forming alpha1 subunits of several types of these channels. The interaction is mediated by the cytoplasmic linker connecting the first and second transmembrane repeats. Within this linker, binding occurs both in the alpha1 interaction domain (AID), which also mediates the interaction between the alpha1 and beta subunits of the channel, and in a second downstream sequence. Further analysis of the binding site showed that several amino-terminal residues in the AID are critical for Gbetagamma binding, defining a site distinct from the carboxy-terminal residues shown to be essential for binding the beta-subunit of the Ca2+ channel. Mutation of an arginine residue within the N-terminal motif abolished betagamma binding and rendered the channel refractory to G-protein modulation when expressed in Xenopus oocytes, showing that the interaction is indeed responsible for G-protein-dependent modulation of Ca2+ channel activity.

Amino Acid Sequence↗
PubMed1997

Report of a collaborative study to establish the international standard for parvovirus B19 serum IgG.

With the introduction of commercial test kits and the wider availability of parvovirus B19 antibody testing, greater standardization is required. Moreover, with a B19 vaccine in the early stages of development, there will be long-term need of accurate measurement of parvovirus B19 antibody levels following natural infection and vaccination. A collaborative study was carried out to assess the suitability of a freeze-dried preparation designated 93/724 to serve as the International Standard for parvovirus B19 serum IgG. The proposed standard, which is a pool of sera from six U.K. blood donors, was assayed along with three coded samples. One was the proposed standard (Preparation A), one a pool of three donor sera (Preparation B) and the third an individual donor serum (Preparation C). These preparations were sent to nine laboratories in seven countries who tested them in 10 different enzyme immunoassays. There were no differences in the antibody content expressed relative to that of the proposed standard in assays using native or recombinant antigen. However, antibody was not detected in serum from an individual blood donor (Preparation C) in assays performed using kits which contained recombinant VP1 but not VP2. This highlights the differences which may be obtained in commercial kits which contain different antigens. The results of this study demonstrated that the proposed standard coded 93/724 is suitable to serve as the International Standard for parvovirus B19 serum IgG and this material has been established as the International Standard for parvovirus B19 IgG by the World Health Organization with an assigned unitage of 100 lU per ampoule. The standard, which is a pool of what can be assumed to be convalescent sera, will be suitable for standardizing diagnostic tests for use in seroprevalence studies and for assessing immunity. An additional standard will be required to standardise tests specifically for the detection of IgM and the diagnosis of acute infection.

Antibodies, Viral↗
PubMed1997

Influence of morphometric factors on quantitation of paracellular permeability of intestinal epithelia in vitro.

PURPOSE: The relative contribution of the small and large intestine to paracellular absorption is a subject of some controversy. Direct comparison of paracellular permeability in different epithelia is complicated by variations in junctional density and/or the absorptive surface area. METHODS: This study used a combination of morphometric analyses and in vitro absorption studies to define permeability characteristics in relation to the amount of paracellular pathway present in rat ileum, colon and the model epithelium, Caco-2. RESULTS: Mucosal to serosal amplification was higher in ileum (3.9) than colon (1.9) or Caco-2 (1). Tight junctional density (lp) of ileal crypts was approximately 3 fold greater (91 m/cm2) than that measured in ileal villi, colonic surface and crypt cells or Caco-2 monolayers (34-37 m/cm2). However, when the relative contributions of the crypts and villi was taken into account there was no significant difference in the mean lp per mucosal area for the three epithelia studied. Using these data to correct for morphometric differences the permeabilities of a range of small hydrophilic molecules (atenolol, D-PheAsp and PEG oligomers MW 282-634) was measured. Permeability of rat ileum and colon were virtually identical for all compounds studied. In contrast, Caco-2 monolayers showed a significantly lower permeability than intestinal tissues with the difference increasing markedly with molecular size. CONCLUSIONS: These studies suggest the importance of accounting for morphological variation when comparing the permeability characteristics of different epithelial systems.

Animals↗
PubMed1997

Influence of proxy respondents and mode of administration on health status assessment following central nervous system tumours in childhood.

Central nervous system (CNS) tumours account for 20% of childhood cancers. Survivors often experience severe physical, neuropsychological and social sequelae of the disease and its treatment. Health status assessment in these individuals is an essential clinical outcome measure, yet little consensus exists regarding the optimum methodology. The influence of proxy respondents (parents, physiotherapists and doctors) and mode of administration (home and clinic) in which assessments is performed has been evaluated in a cohort of 37 survivors of childhood CNS tumours. A health-related quality of life (HRQOL) questionnaire, incorporating the Mark II and III Health Utilities Indices, was completed at home and in clinic by patients and parents. Doctors and physiotherapists completed this questionnaire plus Lansky Play-Performance and Karnofsky Performance scores. No significant differences between raters for single attribute scores occurred either at home or in clinic, although a wide range of agreement (kappa = 0.05-1.00, percentage agreement 53-100%) between observers was revealed. Most agreement occurred between parents and patients: this was greatest on home completion (kappa = 0.48-1.00, percentage agreement 53-100%). Doctors and physiotherapists agreed less on subjective attributes (emotion, cognition and pain). Better if responses were classified as normal and abnormal. Inter-observer agreement was greater for the HRQOL questionnaire than for Karnofsky and Lansky scores. Home completion of questionnaires provides a reliable, acceptable and convenient method of assessing health status.

Adolescent↗