The development of aesthetic responses to music and their underlying neural and psychological mechanisms.

In the field of psychology, the first studies in experimental aesthetics were conducted approximately 140 years ago. Since then, research has mainly concentrated on aesthetic responses to visual art. Both the aesthetic experience of music and, especially, its development have received rather limited attention. Moreover, until now, very little attention has been paid to the investigation of the aesthetic experience of music using neuroscientific methods. Aesthetic experiences are multidimensional and include inter alia sensory, perceptual, affective, and cognitive components. Aesthetic processes are usually experienced as pleasing and rewarding and are, thus, important and valuable experiences for many people. Because of their multidimensional nature, these processes employ several brain areas. In the present review, we examine important psychological and neural mechanisms that are believed to contribute to the development of aesthetic experiences of music. We also discuss relevant research findings. With the present review, we wish to provoke further discussion and possible future investigations as we consider the investigation of aesthetic experiences to be important both scientifically and with respect to potential clinical applications.

Adder bites. A report of 68 cases.

BACKGROUND AND AIMS: The adder (Vipera Berus) is the only venomous snake that exists naturally in Scandinavia. The aim of this study is to estimate the severity of adder bites, to form a general picture of symptoms of bites and to find out how effective the present treatment methods of adder bites are. MATERIAL AND METHODS: 68 true adder bites treated in Turku University Hospital during the years 1995-2000 were reviewed retrospectively. RESULTS: There were no deaths in this material. A bite caused severe symptoms to 10% of the patients. The symptoms were moderate in 21%, mild in 34% and minor in 35% of the cases. Children under 10 years were the proportionally biggest age group and severe poisonings were most frequent among small children. Rapidly progressive oedema, gastrointestinal symptoms, hypotension and early leucocytosis were signs of more severe poisonings. Antivenom therapy with specific ovine Fab antivenom proved to be an effective and safe treatment in severe poisonings. CONCLUSIONS: An adder bite may also cause severe symptoms for adults. All patients should be observed at least few hours after the bite and parental fluid therapy should be started at an early stage. In the treatment of severe poisonings an antivenom therapy should be considered. Rapidly progressive symptoms and early leucocytosis may serve as a warning signal for higher probability of severe reactions.

Acceptability and profile of the clinical drug trials underway in Finnish university hospitals in the 1990s: applications reviewed by ethics committees.

There is scarce information in literature about the decisions made by ethics committees concerning the clinical studies they have reviewed. A retrospective, detailed review of 666 applications, their amendments and the ethics committees' statements was undertaken. All protrocols of clinical studies on medicinal products submitted to and reviewed by the ethics committees of two university hospitals during the years 1992, 1994, 1996 and 1998 were investigated. Most of the studies were international (50%), multicenter (71%), phase III trials (41%) on a new clinical entity, (38%). Validity of the clinical drug study applications was acceptable in more than half of the cases (364; 55%), while 91 (14%) were approved with advisory comments, 153 (23%) had to be amended, 35 (5%) were left pending and 23 (3%) were rejected. Most of the questions pertained to informed consent and the study protcol. In accordance with precious results, our findings support the opinion that the submitted documents need to be improved, especially with regard to informed consent and study protocols, in order to gain better Good Clinical Practice (GCP) compliance. Well-defined, documented operating procedures of the ethics committees would have facilitated the practical issues in the review process.

Haplotypes of the ApoA-I/C-III/A-IV gene cluster and familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is the most frequent familial lipoprotein disorder associated with premature coronary heart disease. However, no genetic defect(s) underlying FCHL has been identified. A linkage between FCHL and the apoA-I/C-III/A-IV gene cluster has been reported but not verified in other populations. A recent study identified FCHL susceptibility haplotypes at this gene cluster. To study whether such haplotypes are also associated with FCHL susceptibility in Finns, we studied 600 well-defined Finnish FCHL patients and their relatives belonging to 28 extended FCHL families by using haplotype, linkage, sib-pair, and linkage disequilibrium analyses. The genotypes of the MspI polymorphisms were associated with total serum cholesterol (P<0.01) and apoB (P<0.05) levels in spouses, which represent the general Finnish population. However, no evidence of direct involvement of any of these loci or their specific haplotypes in the expression of FCHL in the Finnish FCHL families was found.

Enhancement of intermediate-term memory by an alpha-1 agonist or a partial agonist at the glycine site of the NMDA receptor.

The aim of the present study was to investigate whether the activation of alpha-1 adrenergic receptors can influence intermediate-term memory. Therefore, the effects of ST 587 (30 or 100 micrograms/kg), a putative alpha-1 agonist, on the retention of the radial arm task using non-matching to sample with a 4-h delay were investigated in rats. The results indicated that the administration of ST 587 (100 micrograms/kg) before a sampling phase increased the time to complete the sampling phase which was due to an increased number of errors of repetition (regarded as working memory errors) and a reduced number of arms visited in a given time (regarded as behavioral activity). However, this treatment increased the number of correct choices before the first error during the retention phase in this task. Since we were also interested in investigating the role of NMDA receptors in memory encoding, we investigated whether NMDA receptor modulation by d-cycloserine (1 or 10 mg/kg), a partial agonist of the glycine site on the NMDA receptor, had any influence on the performance of rats in this task. The results indicated that d-cycloserine (10 mg/kg) given before the sampling phase did not influence the performance of rats during the sampling phase, but it did improve their choice accuracy during the retention phase of this task. These data suggest that the systemic administration of either an alpha-1 agonist or an indirect agonist of NMDA receptors can facilitate intermediate-term retention of spatial information.

Low field MRI and scaphoid fracture.

18 consecutive patients suspected of and treated for an acute scaphoid fracture were examined by lowfield MRI. This showed 11 fractures while seven scaphoids were considered normal. T1 weighted images showed a fracture as an area of decreased signal intensity. Two radiologically obvious fractures produced normal MR images. These fractures proved to be the result of old trauma. A wide spectrum of additional traumatic lesions in the wrists, not detected by routine X-ray analysis, were also demonstrated. These included seven fragmented triangular fibrocartilages (TFC), torn scapho-lunate ligaments in four cases and one torn triquetro-lunate ligament. Bone bruises of other carpal bones and seven other carpal fractures were also detected. Low field MRI can be used to show scaphoid fractures and allows diagnosis of additional or simulating lesions.

Transarterial brachial plexus anesthesia for hand surgery: a retrospective analysis of 346 cases.

STUDY OBJECTIVES: To study the safety and efficacy of the transarterial approach to brachial plexus block with 60 to 70 ml of local anesthetic solution, and to compare the success and complication rates of this block performed by experienced or inexperienced anesthesiologists. DESIGN: Retrospective analysis of 346 records of ASA physical status I-IV patients who underwent elective unilateral orthopedic upper limb surgery with transarterial plexus anesthesia. SETTING: University teaching hospital. MEASUREMENTS AND MAIN RESULTS: Blood pressure (BP) and heart rate were measured at 5-minute intervals. Analgesia was registered as successful, incomplete, or failed. Any patient complaints or adverse reactions were recorded. The first 60 ml of local anesthetic provided surgical analgesia to 64% of patients. With a supplemental 10 ml of anesthetic, the overall success rate was 94%, with only 19 of 346 patients requiring general anesthesia. Experience in performing the block increased the success rate from 90% to 98% (p < 0.001). Six patients experienced either nausea or a transient BP decrease that did not require medication. There was no record of toxic or other serious adverse reaction. CONCLUSIONS: Transarterial brachial plexus block administered with a 60 to 70 ml dose of local anesthetic provides surgical analgesia for hand surgery with an excellent success rate and without serious adverse effects.

Influence of flumazenil on the learning-enhancing effect of ambocarb in rats.

The effects of flumazenil (Ro 15-1788) and a new beta-carboline, ambocarb (AMB), on learning were investigated using the multichoice maze. The drugs, administered either alone or simultaneously, were injected once a day before training for eight days. AMB, administered alone, improved the performance and decreased the working errors, whilst flumazenil had no effect on performance during its sole administration but weakly prevented the learning-improving effect of AMB. More significantly, flumazenil antagonized the motor activity depressed by AMB. In the study ex vivo, flumazenil decreased and AMB increased the apparent affinity of [3H]flunitrazepam to the central benzodiazepine receptors. Flumazenil reversed the action of AMB on the central benzodiazepine receptors, but failed to reduce significantly the modulative effects of AMB on [3H]muscimol and [35S]t-butylbicyclophosphorothionate ([35S]TBPS) binding. These data indicate that flumazenil, due to its action on the central benzodiazepine receptors, more effectively reverses the inhibition of motor activity than the performance-improving effect of AMB.

Acute neurobehavioural effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) in Han/Wistar rats.

The neurobehavioural effects of a single non-lethal dose (1000 micrograms/kg intraperitoneally) of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were assessed in young male Han/Wistar rats, highly resistant to acute lethality of TCDD. TCDD decreased body weight significantly compared with ad libitum fed controls. TCDD did not change the behaviour or the motility of rats in the open field test 8 days after the treatment nor did it affect the spontaneous motor activity up to 27 days after the exposure. In the elevated plus-maze test for anxiety, TCDD-treated rats did not differ from either ad libitum fed controls or pair-fed controls. In the 24-hr passive avoidance test, the learning of TCDD-treated rats did not differ significantly from that of ad libitum fed controls or pair-fed controls from 8 hr to 16 days after the treatment. TCDD did not affect the motor coordination or the maintenance of balance on the rotating rod but it impaired them slightly in the elevated horizontal bridge test 16 hr after exposure. It did not affect nociception in the hot plate test 16 hr or 8 days after the injection. The results suggest that a single sublethal dose of TCDD does not alter markedly the general behaviour of Han/Wistar rats, in contrast to its striking effect on feeding behaviour which results in a marked decrease in body weight gain.

Amygdala kindling increased fear-response, but did not impair spatial memory in rats.

The behavioral effects of amygdala kindling, a model of experimental epilepsy in rats, are reported. The animals were stimulated twice a day until stage 5 (generalized clonic) seizures were obtained three times. Two weeks later the performance of the amygdala-kindled and sham-operated rats was tested in the open-field test, on the elevated plus maze, elevated bridges, and in the Morris water maze. The results show that amygdala kindling decreased exploratory and other motor activity in the open-field test, had anxiogenic effects on the elevated plus-maze, decreased boldness on the elevated bridges, but had a negligible affect in the spatial memory task. These results suggest that amygdala kindling affects the normal fear reaction of rats, a response that is known to be mediated through the amygdaloid pathways.

Acute neurobehavioural toxicity of trichothecene T-2 toxin in the rat.

The acute effects of single oral doses, 0.4 and 2.0 mg/kg, of trichothecene T-2 mycotoxin on behaviour, motor performance and nociception were studied in male Wistar rats. Both doses are sublethal and did not cause overt acute signs of intoxication. In the open field test, 2.0 mg/kg of T-2 toxin increased motionlessness and decreased sniffing (P less than 0.05) 4 hr after the administration. The higher dose shortened step-through latencies in the test trial of the 24-hr passive avoidance test (two-way shuttle box). The exponential data analysis showed that, in those rats that did not learn to avoid the dark (unsafe) compartment of the box, the retention after 2.0 mg/kg of T-2 toxin was only 25% of that in controls (P less than 0.001). T-2 toxin had no effect on motor coordination in the rotarod test and in the bridge walking test 7-8 hr after administration. T-2 toxin had no effect on nociception in the hot place test 8.5 hr after administration. The results suggest that T-2 toxin has some inactivating effects on behaviour of rats, and it seems to cause an impairment in the passive avoidance test at dose 2.0 mg/kg.

3H-atipamezole binding sites in mouse cerebral cortex: possible involvement of alpha 2-adrenoceptors in sexual behavior.

Atipamezole is a new specific alpha 2-adrenoceptor antagonist. In this study, first, the presence of specific 3H-atipamezole binding sites in the sagittal and coronal sections of mouse brain was established using autoradiography. In vitro experiments with mouse cerebral cortex membranes indicated that d-medetomidine, a new alpha 2-adrenoceptor agonist structurally related to atipamezole, displaces labelled atipamezole more potently than noradrenaline. The saturation isotherm with d-medetomidine demonstrated high affinity binding with the apparent number of binding sites KD 1.36 nM and 760 fmol/mg, respectively. In the next series of experiments male mice were sacrificed immediately after copulation and cerebral cortex 3H-atipamezole and 3H-flumazenil binding was studied. Oxymetazoline and prazosin are known to label preferably alpha 2A and alpha 2B subtypes of alpha 2-adrenoceptors. Therefore, parallelly with noradrenaline both these compounds were used to determine non-specific binding of 3H-atipamezole. When noradrenaline or oxymetazoline were used as displacing agents copulation caused a significant increase of 3H-atipamezole binding sites. No significant changes were observed when prazosin was used. 3H-Flumazenil binding remained unchanged by copulation. The up-regulation of 3H-atipamezole binding sites indicates that not only alpha 2-adrenoceptors in the periphery but also in the CNS may participate in the regulation of sexual behavior. Moreover, in regulation of sexual behavior central alpha 2-adrenoceptors may be more important than benzodiazepine receptors.

Assessment of acute behavioral toxicity of low doses of diisopropylfluorophosphate (DFP) in rats.

The effect on behavior of single subtoxic doses (100 and 600 micrograms/kg i.p., i.e. 1/77 and 1/13 of LD50, respectively) of an organophosphorous compound, diisopropylfluorophosphate (DFP), was studied in male Wistar rats. In the open-field test, the lower dose of DFP tended to increase ambulation, while the higher dose showed a trend towards a decrease in ambulation, rearing and frequency of defecation. In the elevated plus-maze, rotarod, elevated bridges and hot plate tests, DFP-treated rats did not differ significantly from the olive oil-treated controls. DFP significantly impaired the performance of rats in the one-trial passive avoidance task and dose-dependently decreased spontaneous locomotor activity for 4 hours after administration. At the doses used DFP only slightly inhibited acetylcholinesterase activity in the blood and different brain areas. The results show that the higher dose of DFP had an inactivating effect on the behavior of rats, while the lower dose did not markedly change their behavioral pattern. Our findings indicate that anticholinesterase compounds, such as DFP, can alter behavior even after single small subtoxic doses.

The effects of dorsal noradrenergic bundle lesions on spatial learning, locomotor activity, and reaction to novelty.

The dorsal noradrenergic bundle (DNB) of male Wistar rats was lesioned bilaterally using intracerebral injections of 6-hydroxydopamine neurotoxin. Some of the rats were trained in a water maze using an "alternation" strategy, where the two positions of the hidden platform in the pool were changed between successive trials in the daily tests, and other rats in a water maze, where the temperature of the water was lowered to about 11 degrees C. The rats trained in the cold-water maze were also tested in open-field and saccharin neophobia tests. No differences were found between the two groups in learning of water maze tasks or in locomotor activity in the open-field tests. However, the saccharin neophobia test revealed an increased neophobia in the DNB-lesioned rats.

Acute behavioural effects of the organophosphates sarin and soman in rats.

The effects on behaviour of single subtoxic doses of two potent organophosphorous compounds, sarin (isopropyl methylphosphonofluoridate, 12.5 and 50 micrograms/kg, intraperitoneally) and soman (pinacolyl methylphosphonofluoridate, 4 and 20 micrograms/kg, intraperitoneally) were studied in male Wistar rats. In the open field test, soman dose-dependently decreased rearing and ambulation and increased non-mobile exploration. The higher dose of sarin changed only the rearing and grooming behaviour. Sarin and soman decreased locomotor activity on the Animex for at least one hour at the beginning of the monitoring period. In the doses used, both organophosphates inhibited acetylcholinesterase (AChE) activity significantly in the blood. The results suggest that small doses of sarin and soman have inactivating effects on the behaviour of rats. Although the findings cannot be extrapolated directly to behavioural changes in man, they indicate that subtle behavioural dysfunctions could also occur in humans at exposures which do not cause acute toxicity.

Neurobehavioral toxicity with low doses of sarin and soman.

The acute effects of single subtoxic doses (1/48-1/9 of LD50) of two potent organophosphates (OPs), sarin (12.5 and 50 micrograms/kg i.p.) and soman (4 and 20 micrograms/kg i.p.), were studied on behavior, motor performance and nociception in male Wistar rats. On the elevated plus-maze with two open + two closed arms, higher doses of soman and sarin decreased the proportion of entries made onto open arms (p less than 0.05), while the total number of entries onto open + closed arms was unchanged. On the narrow elevated horizontal bridge, the latencies to reach the safe platform were prolonged with the higher dose of sarin (p less than 0.05) but not with that of soman. On the broad and rod bridges, the latencies of OP-treated rats did not differ significantly from those of controls. OPs did not significantly impair either learning frequency in one-trial passive avoidance test, rotarod performance or nociception in hot plate test. The results suggest that in acutely nontoxic doses sarin and soman affect the behavior of rats, and that the action profiles of the OPs differ from each other. Both soman and sarin change the behavior of rats in the plus-maze test but only sarin seems likely to impair motor coordination/balance.