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Biomedical subjects

N Curtis

Publications and source records attributed to N Curtis.

At least 37 records · Page 2Linked to original sources

Adipsia and hypernatraemia in a dog with focal hypothalamic granulomatous meningoencephalitis.

A 7-year-old Doberman was presented with a history of progressive neurological disease of 4 weeks duration. Initially there were episodes of aimless wandering and uncharacteristic aggression, however, the dog was obtunded at presentation. Serum biochemical analysis revealed profound hypernatraemia and moderate hyperproteinaemia. Despite correction of the hypernatraemia by the infusion of hypotonic fluids, the dog continued to periodically exhibit pacing and head pressing. A patchy, ill-defined contrast-enhancing area was evident in the ventral midbrain on computed tomography of the brain. Analysis of the cerebrospinal fluid revealed a mild increase in protein concentration, positive Pandy's test and mild pleocytosis. Because of the poor prognosis, euthanasia and necropsy were performed. Histopathological analysis of the brain revealed a severe focal meningoencephalitis affecting hypothalamic nuclei and mammillothalamic tracts. Destruction of osmoreceptors in the hypothalamus responsible for recognition of thirst is believed to have resulted in adipsia and subsequent hypernatraemia.

Animals↗

Discriminative stimulus properties of the putative dopamine D3 receptor agonist, (+)-PD 128907: role of presynaptic dopamine D2 autoreceptors.

The putative D3 receptor agonist, (+)-PD 128907, is widely used to study the functional relevance of D3 receptors in vivo. Given that non-selective D2/3/4 receptor agonists serve as effective discriminative stimuli in rats we have trained animals to discriminate (+)-PD 128907 (30 microg kg(-1), s.c.) from saline and examined the pharmacological specificity of the response. Consistent with a D3 receptor mediated response, the non-selective D2/3 receptor agonist apomorphine and the D3 preferring agonists 7-OH-DPAT and (-) quinpirole generalised to the cue whilst the D2/3 receptor antagonists haloperidol, raclopride, spiperone and (+)-butaclamol antagonised drug lever responding. In contrast, the D1 selective agonist (+/-)-SKF 81297 and D1/5 selective antagonist, R-(+)-SCH 23390 had no effect. Results also suggest that presynaptic dopamine receptors are involved. Thus the dopamine depleting agent alpha-methyl-p-tyrosine potentiated the effects of a submaximal dose of (+)-PD 128907 whereas amphetamine failed to generalise per se and blocked (+)-PD 128907 lever selection. However, studies using subtype selective antagonists argue against a role for the D3 receptor. Thus the 10-fold selective D2 receptor antagonist L-741,626 blocked the (+)-PD 128907 discriminative stimulus whereas L-745,829 and GR 103,691, antagonists > 40 and > 100-fold selective for D3 receptors, failed to modify the response. These results suggest that presynaptic D2 receptors mediate the discriminative stimulus properties of (+)-PD 128907 and highlight the lack of selectivity of (+)-PD 128907 for D3 receptors in vivo.

Animals↗

Kawasaki disease thirty years on.

This year marks the 30th anniversary of the first description of Kawasaki disease. The disease has emerged as an important cause of acquired heart disease in children. The cause of Kawasaki disease remains unknown and this presents many problems in the diagnosis and management of the disease. This paper reviews recent publications on the pathogenesis, diagnosis, and the short- and long-term management of Kawasaki disease.

Anti-Inflammatory Agents, Non-Steroidal↗

Student athletic trainer perceptions of clinical supervisor behaviors: a critical incident study.

OBJECTIVE: To identify and describe critical helpful and hindering clinical teaching behaviors of supervising athletic trainers, as perceived by student athletic trainers, and to provide a better understanding of the student athletic training experience. DESIGN AND SETTING: The critical incident technique was used to identify critical behaviors of supervising athletic trainers as perceived by student athletic trainers. SUBJECTS: Sixty-four student athletic trainers from 4 undergraduate NATA-approved or CAAHEP-accredited programs volunteered to participate. MEASUREMENTS: The data from the critical incident forms were reviewed for acceptability, inductively analyzed, and categorized. Results are reported in raw numbers and percentages. Examples are provided to illustrate each category. RESULTS: Helpful and hindering supervisor behaviors were identified in 4 major categories and 24 subcategories. Students reported more helpful than hindering behaviors. Students reported mentoring behaviors most often, followed by accep- tance, nurturing, and modeling behaviors. Student athletic trainers wanted to be respected as professionals regarding ability and knowledge. They also desired mentoring through explanation, demonstration, and constructive feedback and nurturing through confidence building and other supportive supervisor behaviors. Students most often identified incidents of humiliating behaviors and lack of availability by the supervisors as hindering the clinical experience. CONCLUSIONS: Supervising athletic trainer behaviors had a profound effect on the professional development of student athletic trainers. Interaction between supervisors and students positively or negatively affected student athletic trainers' growth and development. Selection of supervising athletic trainers, matching of supervisors with students, and training for supervising athletic trainers are important issues that need further investigation. Student athletic trainers can provide insightful information that can be used to better understand and enhance the clinical experience.

Journal Article↗

Kawasaki disease.

Explore the source record for details and available documents.

Child, Preschool↗

Biological profile of L-745,870, a selective antagonist with high affinity for the dopamine D4 receptor.

L-745,870,(3-([4-(4-chlorophenyl)piperazin-1-yl]methyl)-1H- pyrollo[2,3-b] pyridine, was identified as a selective dopamine D4 receptor antagonist with excellent oral bioavailability and brain penetration. L-745,870 displaced specific binding of 0.2 nM [3H] spiperone to cloned human dopamine D4 receptors with a binding affinity (Ki) of 0. 43 nM which was 5- and 20-fold higher than that of the standard antipsychotics haloperidol and clozapine, respectively. L-745,870 exhibited high selectivity for the dopamine D4 receptor (>2000 fold) compared to other dopamine receptor subtypes and had moderate affinity for 5HT2, sigma and alpha adrenergic receptors(IC50 < 300 nM). In vitro, L-745,870 (0.1-1 microM) exhibited D4 receptor antagonist activity, reversing dopamine (1 microM) mediated 1) inhibition of adenylate cyclase in hD4HEK and hD4CHO cells; 2) stimulation of [35S] GTPgammaS binding and 3) stimulation of extracellular acidification rate, but did not exhibit any significant intrinsic activity in these assays. Although standard antipsychotics increase dopamine metabolism or plasma prolactin levels in rodents, L-745,870 (</=30 mg/kg p.o.) had no effect in these assays. The lack of a suitable in vivo assay for D4 receptor activation prompted the use of in vivo surrogate marker assays which confirmed that doses of 5-60 microg/kg L-745,870 would be sufficient to occupy 50% D4 receptors in the brain. These results show that dopamine D4 receptor antagonism in the brain does not result in the same neurochemical consequences (increased dopamine metabolism or hyperprolactinemia) observed with typical neuroleptics.

Animals↗

L-745,870, a subtype selective dopamine D4 receptor antagonist, does not exhibit a neuroleptic-like profile in rodent behavioral tests.

This study examined the high-affinity, selective dopamine D4 receptor antagonist, L-745,870 (3-([4-(4-chlorophenyl)piperazin-1-yl]methyl)-1H-pyrrolo[2, 3-b]pyridine) in rodent behavioral models used to predict antipsychotic potential and side-effect liabilities in humans. In contrast to the classical neuroleptic, haloperidol, and the atypical neuroleptic, clozapine, L-745,870 failed to antagonize amphetamine-induced hyperactivity in mice or impair conditioned avoidance responding in the rat at doses selectively blocking D4 receptors. Furthermore, L-745,870 failed to reverse the deficit in prepulse inhibition of acoustic startle responding induced by the nonselective dopamine D2/3/4 receptor agonist apomorphine, an effect which was abolished in rats pretreated with the D2/3 receptor antagonist, raclopride (0.2 mg/kg s.c.). L-745,870 had no effect on apomorphine-induced stereotypy in the rat but did induce catalepsy in the mouse, albeit at a high dose of 100 mg/kg, which is likely to occupy dopamine D2 receptors in vivo. High doses also impaired motor performance; in rats L-745,870 significantly reduced spontaneous locomotor activity (minimum effective dose = 30 mg/kg) and in mice, L-745,870 reduced the time spent on a rotarod revolving at 15 rpm (minimum effective dose = 100 mg/kg). Altogether these results suggest that dopamine D4 receptor antagonism is not responsible for the ability of clozapine to attenuate amphetamine-induced hyperactivity and conditioned avoidance responding in rodents. Furthermore, the lack of effect of L-745,870 in these behavioral tests is consistent with the inability of the compound to alleviate psychotic symptoms in humans.

Amphetamine↗

Evidence for a superantigen mediated process in Kawasaki disease.

The clinical, pathological, and immunological similarities between Kawasaki disease and the staphylococcal and streptococcal toxic shock syndromes suggest that a superantigen toxin may be involved in the pathogenesis of the disease. The V beta repertoire of peripheral blood mononuclear cells from 21 children with Kawasaki disease, 28 children with other illnesses, and 22 healthy controls were examined using monoclonal antibodies to V beta 2, 5, 8, 12, and 19. The mean percentage of V beta 2 expressing T cells in the patients with Kawasaki disease was increased when compared with healthy controls or children with other illnesses. The mean percentages of V beta 5, 8, 12, and 19 expressing T cells were also increased in the patients with Kawasaki disease compared with healthy controls, but were not increased when compared with children with other illnesses. The selective use of V beta 2 supports the hypothesis that a superantigen is involved in the pathogenesis of Kawasaki disease.

Acute Disease↗