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Biomedical subjects

J Stewart

Publications and source records attributed to J Stewart.

At least 109 records · Page 6Linked to original sources

From autopoiesis to semantic closure.

This article addresses the question of providing an adequate mathematical formulation for the concepts of autopoiesis and closure under efficient cause. What is required is metaphorically equivalent to reducing the act of writing to a set of mathematical equations, habitually effected by a human mathematician, within the ongoing function of the system itself. This, in turn, raises the question of the relationship between autopoiesis and semantics. The hypothesis suggested is that whereas semantics clearly requires autopoiesis, it may be also be the case that autopoiesis itself can only be materially realized in a system that is characterized by a semantic dimension.

Humans↗

Evaluation of the information and support services in the voluntary sector using a new P-C-P (pivotal-core-peripheral) attributes model.

This paper describes the development and use of a modified SERVQUAL research instrument for measuring the service quality of voluntary organizations from the perspective of their 'customers'. A series of focus group meetings were run with providers and users of the services to identify the appropriate dimensions of service quality. These were structured meetings led by the researchers addressing set questions in a group setting. The meeting enabled the identification of six different dimensions of service quality which neatly mapped on to the pivotal-core-peripheral (P-C-P attributes model [Philip and Hazlett, 1997]), which was developed after extensive research of existing models such as SERVQUAL. These dimensions were used to develop a questionnaire to assess service quality within the voluntary sector. The questionnaire was distributed to 2005 service users, representing eight voluntary organizations from across Northern Ireland. The research resulted in the development of a methodology and research instrument suitable for measuring service quality in the voluntary sector.

Community Mental Health Centers↗

Detection of Sarcocystis neurona in the brain of a Grant's zebra (Equus burchelli bohmi).

An 8-yr-old intact male Grant's zebra (Equus burchelli bohmi) was referred to the Veterinary Medical Teaching Hospital of the University of California-Davis after being found in the owner's pasture obtunded and in lateral recumbency. The animal was hypothermic, weak, and unwilling to rise. There was no evidence of trauma, and the zebra had seemed normal the preceding evening. There was no extensor rigidity, and cranial nerve reflexes were normal. Flexor and extensor reflexes were weak upon initial examination. A complete blood count and serum biochemistry analysis revealed a mild leukocytosis, hyperfibrinogenemia, hypoglycemia, hyponatremia, hypochloremia, hypocalcemia, and hypoalbuminemia. Urinalysis was normal, and a urine toxicology screen for alkaloids was negative. No toxic substance was found in the hay or pasture grasses although the owner reported the presence of yellow star thistle and mushrooms in the pasture. The cerebrospinal fluid cytologic and biochemical analyses were normal, but antibodies to Sarcocystis neurona were detected. The zebra died despite aggressive supportive therapy over a 4-day period. The necropsy demonstrated severe gastrointestinal nematodiasis that could account for hypoalbuminemia and electrolyte abnormalities. Histopathologic examination of the nervous system revealed focal areas of perivascular cuffing in the brainstem that were comprised mainly of lymphocytes, monocytes, and plasma cells. Immunohistochemical staining identified the presence of S. neurona merozoites associated with the lesions. This zebra probably died from severe endoparasitism that resulted in malabsorption, weakness, and recumbency rather than from encephalitis associated with S. neurona merozoites. Equine protozoal myeloencephalitis has not been reported previously in nondomestic equids.

Animals↗

Association of interleukin-1 gene polymorphisms with Alzheimer's disease.

Interleukin-1 (IL-1) is markedly overexpressed in Alzheimer's disease. We found the IL-1A 2,2 genotype in 12.9% of 232 neuropathologically confirmed Alzheimer's disease patients and 6.6% of 167 controls from four centers in the United Kingdom and United States (odds ratio, 3.0; controlled for age and for ApoE [apolipoprotein E] genotype). Homozygosity for both allele 2 of IL-1A and allele 2 of IL-1B conferred even greater risk (odds ratio, 10.8). IL-1 genotypes may confer risk for Alzheimer's disease through IL-1 overexpression and IL-1-driven neurodegenerative cascades.

Aged↗

Pathways to relapse: the neurobiology of drug- and stress-induced relapse to drug-taking.

Relapse is a major characteristic of drug addiction, and remains the primary problem in treating drug abuse. Without an understanding of the factors that determine renewed drug-seeking, the urge to use drugs, and the persistent craving for them, it is unlikely that health care professionals can provide effective treatment. Using an animal model of relapse, the author and her team are studying factors that induce reinstatement of drug-taking behaviour after short and long periods of abstinence, and they are exploring the neurobiological basis of these effects. In their experiments, rats are trained to self-administer drugs intravenously by pressing 1 of 2 levers. During a subsequent period, the drug is no longer available, but the rats are free to try to obtain the drug (a period of "extinction training"). After extinction of responding, the investigators test for the ability of various events to reinitiate drug-seeking. On this background of renewed drug-seeking or relapse, the investigators search for pharmacological and neurochemical manipulations that might block or attenuate such behaviour. They have found that the 2 most effective events for reinstating responding after both short and long drug-free periods are re-exposure to the drug itself and exposure to a brief period of stress. The critical neurochemical pathways mediating drug-induced relapse are not identical to those mediating stress-induced relapse. Relapse induced by "priming" injections of heroin or cocaine involves activation of the mesolimbic dopaminergic pathways, whereas relapse induced by stress involves actions of corticotropin-releasing factor (CRF) in the brain, and of brain noradrenergic (NE) systems. In addition, evidence shows that CRF and NE may interact at the level of the bed nucleus of the stria terminalis in stress-induced relapse. By contrast, relapse induced by "priming" injections of drugs is relatively unaffected by manipulation of CRF and NE systems of the brain.

Animals↗

Pilot study for appropriate anti-infective community therapy. Effect of a guideline-based strategy to optimize use of antibiotics.

OBJECTIVE: To determine whether a community-wide, multi-intervention educational strategy (CoMPLI model) could enhance adoption of clinical guidelines and improve the use of antibiotics. DESIGN: Before-after trial using baseline and study periods with a control group. SETTING: A small community in central Ontario. PARTICIPANTS: Health professionals, the general public, and the pharmaceutical industry. INTERVENTIONS: The educational strategy (CoMPLI), carried out during 6 winter months, consisted of continuing medical education sessions for health professionals and pharmaceutical representatives and a parallel public education campaign that included town hall meetings and pamphlets distributed by local pharmacists. The two main messages were: do not use antibiotics for viral respiratory infections, and use drugs recommended in the publication, Anti-infective Guidelines for Community-Acquired Infections. MAIN OUTCOME MEASURES: Total number of antibiotic claims and adjusted odds ratios (OR) were used to measure the likelihood of physicians prescribing first- or second-line agents compared with the previous year and compared with control physicians. RESULTS: Claims in the study community decreased by nearly 10% during the 6-month study period compared with the baseline period from the previous year. Study physicians were 29% less likely (OR-1 = 0.71, range 0.67 to 0.76) to prescribe second-line antibiotics during the study period than physicians in the rest of the province. CONCLUSIONS: Physicians participating in the pilot study were more likely to follow drug recommendations outlined in published guidelines.

Adult↗

Detection of IgM to hepatitis B core antigen in a reductant containing, chemiluminescence assay.

The Abbott PRISM(R) hepatitis B core (HBc) antigen assay is an automatic in vitro competitive chemiluminescence immunoassay for the detection of total antibody to HBc (anti-HBc) antigen in human serum or plasma. The assay utilizes cysteine solution as a reducing reagent in order to maximize specificity. To help understand the effect of cysteine on detection of anti-HBc antigen, we separated and purified anti-HBc IgM and IgG from human plasma using size exclusion, protein A/G, and affinity chromatography techniques. We showed that cysteine affected the reactivity of anti-HBc IgM with recombinant HBc (rHBc) antigen but not the reactivity of anti-HBc IgG. Anti-HBc IgM treated with cysteine yielded byproducts which were reactive in the PRISM HBcore assay. Reduction-sensitive factor (RSF) - IgM fraction from serum known to be non-specific for anti-HBc activity, similarly treated with cysteine, was no longer reactive in the PRISM HBcore assay. We showed that cysteine treatment is effective against non-specific IgM in human blood. Also, the inclusion of cysteine in the PRISM HBcore assay does not compromise the detection of HBc specific antibodies.

Antibody Specificity↗

A role for the bed nucleus of the stria terminalis, but not the amygdala, in the effects of corticotropin-releasing factor on stress-induced reinstatement of cocaine seeking.

We have shown that intracerebroventricular administration of the corticotropin-releasing factor (CRF) receptor antagonist D-Phe CRF(12-41), blocks footshock-induced reinstatement of drug seeking in cocaine-trained rats. We now report that D-Phe acts in the bed nucleus of the stria terminalis (BNST), and not in the amygdala, to block footshock-induced reinstatement of cocaine seeking. In addition, CRF injections in the BNST, and not in the amygdala, are sufficient to reinstate cocaine seeking. Rats were trained to self-administer cocaine intravenously on a fixed ratio (FR-1) schedule of reinforcement. After 5 drug-free days, animals were returned to the self-administration chambers and given daily extinction and reinstatement test sessions. To test the effects of D-Phe CRF(12-41) on stress-induced reinstatement, rats were pretreated with vehicle or D-Phe in either the BNST (10 or 50 ng per side) or amygdala (50 or 500 ng per side) before being exposed to 15 min of intermittent footshock stress. To test whether injections of CRF itself could induce reinstatement, rats were given vehicle or CRF in either the BNST (100 or 300 ng per side) or amygdala (300 ng per side) 15 min before the session. Injections of D-Phe into the BNST completely blocked footshock-induced reinstatement of cocaine seeking; injections of CRF itself in this structure induced reinstatement. Injections of these compounds into the amygdala were without effect. These findings suggest that activation of CRF receptors in the BNST, but not in the amygdala, is critical for footshock-induced reinstatement of cocaine seeking.

Amygdala↗

Ovariectomy of adult rats leads to increased expression of astrocytic basic fibroblast growth factor in the ventral tegmental area and in dopaminergic projection regions of the entorhinal and prefrontal cortex.

Changes in astrocytic function may underlie the neurochemical and morphological alterations in limbic and cortical areas after estrogen loss in adult females. We assessed whether increased expression of basic fibroblast growth factor (bFGF), an astrocytic response involved in injury-induced neuronal plasticity, occurs after ovariectomy. We examined bFGF immunoreactivity (IR) in ovariectomized rats with oil or estradiol benzoate (5 microgram every 4 d; Experiment 1) and in ovariectomized and intact animals (Experiment 2). In the ventral tegmental area (VTA), bFGF-IR and glial fibrillary acidic protein (GFAP)-IR were greater in ovariectomized animals than in animals with estrogen replacement. bFGF-IR in the VTA was greater in ovariectomized than in intact females. In the dorsal raphe, no differences between groups were found in GFAP-IR or bFGF-IR. In mesolimbic dopaminergic target areas within entorhinal cortex (Ent), prefrontal cortex, and nucleus accumbens, bFGF-IR was higher in Ent of ovariectomized animals 4 weeks after surgery in both experiments, but no differences were seen in nucleus accumbens or in an occipital cortical, control, area in either study. In Experiment 2, small increases in bFGF-IR were seen in the prefrontal cortex after ovariectomy. In the VTA and Ent, changes in bFGF-IR developed gradually, peaking at 4 weeks and waning at 40 weeks. Furthermore, increased dendritic arbor of Ent layer II/III pyramidal cells was found in ovariectomized females with the use of a modified Golgi-Cox staining procedure. These findings suggest that, within specific regions, ovariectomy induces astrocytic responses similar to those observed after injury that may affect neuronal chemistry and morphology.

Animals↗

In rats, odor-induced Fos in the olfactory pathways depends on the phase of the circadian clock.

We used immunostaining for Fos to study the effect of circadian clock phase on odor-induced neuronal activation in the olfactory system in rats. Brief presentation of cedar odor to rats housed in constant darkness stimulated Fos expression in the main olfactory bulb, anterior olfactory nucleus, piriform cortex, and several other odor-responsive structures, both in the subjective day and subjective night phases of the cycle. Fos expression in response to odor, but not basal expression, was greatly enhanced in the subjective night in all structures examined. These findings are consistent with the idea that odor-induced neuronal activation in the olfactory pathways is modulated by the phase of the circadian clock.

Animals↗

Identifying appropriate tasks for the preregistration year: modified Delphi technique.

OBJECTIVES: To identify the tasks that should constitute the work of preregistration house officers to provide the basis for the development of a self evaluation instrument. DESIGN: Literature review and modified Delphi technique. SETTING: Northern Deanery within the Northern and Yorkshire office NHS executive. SUBJECTS: 67 educational supervisors of preregistration house officers. MAIN OUTCOME MEASURES: Percentage of agreement by educational supervisors to tasks identified from the literature. RESULTS: Over 61% of communication items, 70% of on call patient care items, 75% of routine patient care items, 45% of practical procedure items, and over 63% of self management items achieved over 95% agreement that they should be part of the house job of preregistration house officers. Poor agreement was found for the laboratory and clinical investigations that house officers could perform with or without supervision. CONCLUSIONS: The tasks of house officers were identified but issues in using this method and in devising a universally acceptable list of tasks for preregistration house officers were apparent.

Clinical Laboratory Techniques↗

Functional activation of punch-cultured magnocellular neuroendocrine cells by glutamate receptor subtypes.

To provide a simple means to isolate and study the cellular functions of small groups of neurons, we developed a modified 'punch' culture procedure that facilitates acute and long-term in vitro physiological studies. Primary 'punch' cultures of magnocellular neuroendocrine cells (MNCs) from the supraoptic nucleus (SON) were established and the basic physiological effects of subtype-specific glutamate receptor agonists were characterized. MNCs from the punch cultures established a mature morphology in culture with extensive outgrowth of axons and varicosities. After 8 days, a single cultured SON punch produced an average of 10.0 +/- 2.1 pg AVP and contained an average of 222 +/- 53 vasopressin-neurophysin immunoreactive cells. Patch clamp recordings from MNCs demonstrated the presence of N-methyl-D-aspartate (NMDA)-sensitive and DL, alpha-amino-3-hydroxy-5-methylisoxazole propionic acid (AMPA)-receptors. Stimulation of metabotropic receptors with 1S,3R ACPD induced acute or gradual increases in intracellular calcium. NMDA, AMPA and metabotropic receptors all contributed to the secretion of vasopressin from the punch cultures with an agonist rank order potency of: NMDA (10 microM) > AMPA (1 microM) = 1S,3R ACPD (100 microM) > kainate (10 microM). This culture preparation should be useful for cellular studies of small groups of neuroendocrine and other cells.

Animals↗