1 Gabapentin (neurontin) is a novel antiepileptic agent that binds to the a 2 d subunit of voltagedependent calcium channels. The only other compound known to possess a nity for this recognition site is the (S)-(+)-enantiomer of 3-isobutylgaba. However, the corresponding (R)-(7)-enantiomer is 10 fold weaker. The present study evaluates the activity of gabapentin and the two enantiomers of 3-isobutylgaba in formalin and carrageenan-induced in¯ammatory pain models. 2 In the rat formalin test, S-(+)-3-isobutylgaba (1 ± 100 mg kg 71 ) and gabapentin (10 ± 300 mg kg 71 ) dose-dependently inhibited the late phase of the nociceptive response with respective minimum e ective doses (MED) of 10 and 30 mg kg 71 , s.c. This antihyperalgesic action of gabapentin was insensitive to naloxone (0.1 ± 10.0 mg kg 71 , s.c.). In contrast, the R-(7)-enantiomer of 3-isobutylgaba (1 ± 100 mg kg 71 ) produced a modest inhibition of the late phase at the highest dose of 100 mg kg 71 . However, none of the compounds showed any e ect during the early phase of the response. 3 The s.c. administration of either S-(+)-3-isobutylgaba (1 ± 30 mg kg 71 ) or gabapentin (10 ± 100 mg kg 71 ), after the development of peak carrageenan-induced thermal hyperalgesia, dosedependently antagonized the maintenance of this response with MED of 3 and 30 mg kg 71 , respectively. Similar administration of the two compounds also blocked maintenance of carrageenan-induced mechanical hyperalgesia with MED of 3 and 10 mg kg 71 , respectively. In contrast, R-(7)-3-isobutylgaba failed to show any e ect in the two hyperalgesia models. 4 The intrathecal administration of gabapentin dose-dependently (1 ± 100 mg/animal) blocked carrageenan-induced mechanical hyperalgesia. In contrast, administration of similar doses of gabapentin into the in¯amed paw was ine ective at blocking this response. 5 Unlike morphine, the repeated administration of gabapentin (100 mg kg 71 at start and culminating to 400 mg kg 71 ) over 6 days did not lead to the induction of tolerance to its antihyperalgesic action in the formalin test. Furthermore, the morphine tolerance did not cross generalize to gabapentin. The s.c. administration of gabapentin (10 ± 300 mg kg 71 ), R-(7) (3 ± 100 mg kg 71 ) or S-(+)-3-isobutylgaba (3 ± 100 mg kg 71 ) failed to inhibit gastrointestinal motility, as measured by the charcoal meal test in the rat. Moreover, the three compounds (1 ± 100 mg kg 71 , s.c.) did not generalize to the morphine discriminative stimulus. Gabapentin (30 ± 300 mg kg 71 ) and S-(+)-isobutylgaba (1 ± 100 mg kg 71 ) showed sedative/ ataxic properties only at the highest dose tested in the rota-rod apparatus. 6 Gabapentin (30 ± 300 mg kg 71 , s.c.) failed to show an antinociceptive action in transient pain models. It is concluded that gabapentin represents a novel class of antihyperalgesic agents.
The effect of neuropeptide cholecystokinin (CCK) receptor agonists and antagonists was examined in the rat elevated X-maze model of anxiety. The selective CCK-B receptor antagonists CI-988 (PD 134308) and L-365,260 produced anxiolytic-like effects, whereas MK-329, a CCK-A receptor antagonist, was respectively less potent by factors of 313 and 200. The intracerebroventricular administration of the nonselective CCK receptor agonist caerulein or the selective CCK-B receptor agonist pentagastrin increased dose dependently the level of anxiety. CI-988 dose dependently antagonized the anxiogenic response to pentagastrin but not that induced by pentylenetetrazol. These results strongly suggest that activation of the brain CCK-B receptor induces anxiety and that selective antagonists of this receptor represent a separate class of anxiolytic agents.Although originally described as a hormone in the gastrointestinal tract (1), cholecystokinin (CCK) also has been shown to be present in high concentrations in certain neurones ofthe brain (2), where it exists as the octapeptide CCK-8 in the sulfated (CCK-8S) and desulfated forms (3, 4). Receptors for CCK have been divided into two types: (i) the CCK-A receptor that is blocked selectively by L-364,718 and is found in peripheral tissues as well as discrete brain areas (6, 7), and (ii) the CCK-B receptor that is present throughout the brain (6) and is characterized by a high affinity for the novel antagonists CI-988 (PD 134308) and L-365,260 (8, 9). The CCK-B receptor is similar or identical to the peripheral gastrin receptor (9). CCK is present in high concentrations in the limbic system (10), an area involved in the control of emotion and anxiety. Furthermore, in some neurones CCK coexists with other neurotransmitters including y-aminobutyric acid (GABA) (11,12), and agents that modify GABAergic neurotransmission in the brain (13)-for example, benzodiazepines-possess anxiolytic properties (14). These observations prompted us to study the role of CCK in anxiety, and recently we reported that a CCK receptor antagonist, CI-988, produces anxiolytic effects in a number of animal models of anxiety (8). However, this study has raised several important MATERIALS AND METHODSAnimals. Male hooded Lister rats (200-250 g) were obtained from Olac (Bichester, U.K.). Animals were housed in groups offive under a 12-hr light/dark cycle (lights on at 0700) with food and water ad libitum.Implantation of Intracerebroventricular (i.c.v.) Cannulas. For i.c.v. administration, rats were anesthetized by using a mixture of diazepam (2.5 mg/kg of body weight, i.p.) and Hypnorm (0.315 mg of fentanyl citrate and 10 mg of fluanisone per ml; 0.2 ml/kg). A 22-gauge stainless-steel guide cannula was implanted unilaterally by using a Kopf stereotaxic frame [anterior-posterior = 8.2 mm anterior of interaural line; lateral = +1.4 mm; dorsoventral = 6.6 mm dorsal to the interaural line according to the atlas of Paxinos and Watson (18)]. Animals were allowed 5-7 days to recover from surgery before behav...
Emergency physicians should not interpret CT scans for trauma without extra training.
Although there appears to be broad agreement among opinion leaders regarding the concepts underpinning existing prehospital critical care services, areas of contention are highlighted that may help explain the current lack of consensus. Cooperative efforts to assess the current demand and clinical evidence would assist in the creation of a joint consensus and allow effective future planning for the provision of prehospital critical care throughout the UK.
Purpose: This study aims to qualitatively explore radiographers' learning needs and to better understand important learning arenas for radiographers in order to promote lifelong learning (LLL). Lifelong learning and continuing professional development (CPD) are both activities and catalysts for exploring the learning needs of radiographers. Investigating radiographers' learning needs and the location for best learning is important in order to effectively utilise current and future CPD programmes and directives. Methods: Six radiographers working in a public Norwegian medical imaging department (MID) took part in the study. A combination of individual interviews and a focus group were used. Grounded Theory (GT) was used to qualitatively explore the learning needs and learning arenas important to these radiographers. Results: The radiographers defined their work place as the best learning arena. On‐the‐job training, knowledge sharing through peer practice and interdisciplinary collaboration were important in the learning process. The radiographers placed a strong importance on technical sub‐specialising in modalities as well as reflecting on the completeness in the radiographic role. The need for a better merge between theoretical education and applied radiographic practice was identified. Conclusion: Experiential learning was found to be central to the radiographers' learning. The learning needs of the radiographers embraced specialisation as well as the theoretical domain and there was evidence that the rapid technological pace impacted upon the radiographers' sense of achievement, motivation and adequacy. The participating radiographers acknowledged the necessity of lifelong learning, but also called to attention the importance of collegial guidance, interprofessional collaboration and feedback in creating a reflective practitioner.
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