Effect of trail design and grooming on the incidence of injuries at alpine ski areas.

OBJECTIVES: To identify the conditions at certain sites on slopes known as black spots for injury. METHOD: In the Hafjell and Voss alpine ski areas in Norway, 1410 skiing injuries were recorded from December 1990 through the 1996 season. In Hafjell, 183 of these injuries were plotted on an area map during the two first seasons. Similarly, in Voss, 214 injuries were plotted on an area map for two seasons. During the last three seasons in Hafjell, 835 ski injuries were related to 6712 snow grooming hours and 6,829,084 lift journeys. RESULTS: The mean injury rate was 2.2 injuries per 1000 skier days, and the mean injury severity score (ISS) was 3.1. Accumulations of injuries at three sites (black spots) were recorded on the Hafjell area map. These injuries represented 40% of all injuries in the alpine area (p<0.05). Seven injury accumulation sites were recorded on the alpine area map of Voss, representing 22% of the total injuries (p>0.05). Grooming of the slopes was rated poor for the 49% of injuries that occurred at the sites of injury concentration and significantly different (27%) from injuries that occurred at random in Hafjell. The corresponding values in Voss were 50% and 25% respectively. Grooming hours appeared to be inversely proportional to the number of injuries: R = -0.99 (p<0.02). The mean ISS declined significantly in Hafjell over the observation period (p<0.001). CONCLUSION: Inappropriate trail design and slope grooming seem to result in an accumulation of injuries at certain sites. Modification in construction and maintenance of the courses may reduce the number of injuries and mean ISS.

Abnormal serotonin reuptake in an overtrained, insomnic and depressed team athlete.

The purpose of this report is to study serotonin reuptake of the brain in a severely overtrained athlete by using single-photon emission computed tomography (SPECT). A 26-year-old team athlete increased his training volume (by 200 %) and intensity markedly in a new high-level team. After two months, he started to feel continuous fatigue. He had tinnitus in his left ear, he felt disturbing palpitation and had pollacisuria. After four months, he started to suffer from insomnia. He still continued to play for another three months, after which he was unable to play. He could only sleep for 3 to 4 hours per night. Only minor abnormalities could be found in extensive physical and laboratory examinations. The athlete had a severe overtraining state. In the brain SPECT scans, using the specific radioligand for serotonin transporter imaging ( (123)I labelled 2beta-carbomethoxy-3beta-[4-iodophenyl]-nortropane), low activity areas were detected in the midbrain, anterior gingulus, and left frontal and temporo-occipital lobes. In a psychiatric examination, the patient was found to have signs of major depression, which he hardly recognized himself. We conclude, that that the severe overtraining state could have been related to decreased serotonin reuptake in the brain and signs of major depression.

Organisation of safety measures in an Alpine World Junior Championship.

OBJECTIVES: To study the implementation of skiing safety during the Alpine World Junior Championship of 1995. METHODS: A map of the area was made with descriptions of the slopes and all its facilities and the security measures along the course. The number of competitors who started and any injuries reported were recorded in a questionnaire. RESULTS: A total of 452 girls and 546 boys started in the different races. Only four injuries were recorded, all in girls. The overall injury rate was 4 per 1000 runs. An injury rate of 8.3 per 1000 runs was recorded in the downhill. One skier had a possibly severe injury (ISS = 14) in the downhill; the rest of the injuries were minor (ISS = 1). The mean ISS was 4.3 and the total ISS was 17. CONCLUSIONS: A significantly higher injury rate was recorded for young female than young male racers. The injury rate was significantly higher in downhill than the other alpine disciplines in the Alpine World Junior Championship. The injury rate was not significantly different from that recorded one year previously for Olympic racers, and juniors therefore need the same safety measures as Olympic racers.

Effects of ageing on serotonin transporters in healthy females.

The effect of ageing on brain serotonin transporters was evaluated in 19 healthy female volunteers (age range 22-74 years) using single-photon emission tomography and [123I]nor-beta-CIT. The study subjects were scanned 0.3, 3, 6 and 23 h after injection of 185 MBq of [123I]nor-beta-CIT. The ratio of the distribution volume for tracer in the midbrain to that in the cerebellum minus 1 was used as an index for serotonin transporter binding. An age-related decline of 2% per decade (r=-0.47; P<0.05) was found in the midbrain. The decline in [123I]nor-beta-CIT binding in the serotonin transporter-rich area is much less than that in dopamine transporters in the striatum (6% per decade).

Reduced serotonin transporter binding in binge eating women.

RATIONALE: There is evidence that abnormalities in brain dopamine, norepinephrine and serotonin metabolism may play an important role in binge eating. Serotonin-active antidepressant drugs have also been found to decrease binge eating. OBJECTIVE: We investigated serotonin transporter binding in obese binge-eating women. Eleven obese binge-eating and seven obese control women participated in the study. The subjects were not taking any medication known to affect serotonin (5-HT) transporters. METHODS: We used single-photon emission tomography (SPECT) with the radioligand 123I-labelled nor-beta-CIT, which specifically labels 5-HT transporters. RESULTS: Obese binge-eating women showed significantly decreased 5-HT transporter binding in the mid-brain compared with obese controls (2.1 +/- 0.5 versus 2.9 +/- 0.5, respectively). CONCLUSIONS: SPECT imaging with a ligand specific for 5-HT transporters can be used to assess altered serotonin transporter binding in the living human brain. The results tentatively suggest that 5-HT transporter binding is decreased in binge-eating women.

Dopamine transporter in vitro binding and in vivo imaging in the brain.

Much research interest has lately been focused on the dopamine transporter function in brain. Recent findings indicate that dopamine reuptake is more like a highly regulated than a constitutive determinant of dopamine clearance. Positron emission tomography (PET) and single-photon emission tomography (SPET) offer unique methods to study dopamine transporter function. Results from in vivo PET and SPET studies correspond well with in vitro studies performed on post mortem human brain tissue. Considering some of the variances between in vitro and in vivo receptor binding phenomena it may be that the role of a compound to alter binding to monoamine uptake sites in vitro does not indicate its potential to affect monoamine transporters after administration in vivo. This discrepancy may be better understood taking into account recent studies indicating the possibility of a rapid regulation of transporter function and surface expression. Furthermore, the dopamine transporter is a fruitful target for CNS drug discovery. Fundamental nature of drug actions in vivo may be studied using demonstrated in vitro and in vivo imaging methods.

Activity-related knee injuries and pain in athletic adolescents.

By collecting data from 45 students at a ski high school, we found that a total of 73% of the students reported activity-related pain/injuries of the knee. Sixty-one percent had overuse injuries, 27% malalignment, and 12% had indistinct knee pain. Females suffered more knee pain/injuries (88%) than males (57%). Significantly higher Q-angle degrees were recorded for females (16) than for males (10). "Jumper's knee" was found in all competitive students with a KT manual maximum difference (MMD) of 3 mm or more (mean 4 mm), with a hard endpoint, whereas this was less common among the other competitive students (P < 0.05). The students were given counselling about training and physiotherapy. In the follow-up study 1 year later, a significant reduction of knee pain/overuse injuries, from 73% to 35%, was recorded. This may be related to better equipment, the development of techniques, and training of the muscles. A high volume of training and knee instability, with MMD of 3 mm or more, seemed to be correlated with an increased risk for "jumper's knee" and, possibly, for skiing injuries. By identifying those at increased risk, preseason recommendations can be made and ski injuries may be prevented.

SPET imaging of central muscarinic acetylcholine receptors with iodine-123 labelled E-IQNP and Z-IQNP.

1-Azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (IQNP) is a muscarinic acetylcholine receptor (mAChR) antagonist and the racemic ligand contains eight stereoisomers. In a single-photon emission tomography (SPET) study in monkeys we recently confirmed that [123I]E-(R,R)-IQNP ([123I]E-IQNP) is a radioligand with modest selectivity for the M1 and M4 subtypes, whereas [123I]Z-(R,R)-IQNP ([123I]Z-IQNP) is non-subtype selective. In the present SPET study, E- and Z-IQNP were examined in human subjects. SPET examination was performed on three male subjects after i.v. injection of [123I]E-IQNP and in another three after i.v. injection of [123I]Z-IQNP. The binding potential (BP) for [123I]E-IQNP was calculated using several quantitative approaches with the cerebellum as a reference region. High-performance liquid chromatography was used to measure radioligand metabolism in plasma. Following [123I]E-IQNP, the radioactivity was high in the neocortex and striatum, intermediate in the thalamus and low in the pons and cerebellum, which is consistent with the rank order for the regional density of M1 and M4 subtypes in vitro. For all regions, peak equilibrium was identified within the 48-h data acquisition. The simplified reference tissue approach using SPET data from 0 to 48 h was the most reliable in this limited series of subjects. Following injection of [123I]Z-IQNP, radioactivity was high in the neocortex and striatum, intermediate in the thalamus and pons and low in the cerebellum, which is in agreement with the density of M1, M2 and M4 subtypes as measured in vitro. Quantitative analyses provided indirect support for specific M2 binding of Z-IQNP in the cerebellum. The high selectivity of [123I]E-IQNP for M1 and M4 receptors allowed the use of cerebellum as a reference region devoid of specific binding, and may be advantageous for applied clinical studies of M1 and M4 receptors binding in man. [123I]Z-IQNP has potential for exploration of M2 receptor binding in the cerebellum.

Specific binding and laterality of human extrastriatal dopamine D2/D3 receptors in late onset type 1 alcoholic patients.

Late onset type 1 alcoholism has been suggested to be associated with decreased dopaminergic transmission. Our hypothesis was that late onset type 1 alcoholics have also abnormal extrastriatal dopamine D(2)/D(3) receptor distribution. We performed binding, heterogeneity and laterality analysis of extrastriatal and striatal dopamine D(2)/D(3) receptors in nine late onset male alcoholics and in 12 age-matched healthy males. A radioligand, [(123)I]epidepride was used in high resolution single-photon emission tomography (SPET). Specific binding of epidepride in the left temporal pole was significantly (P<0.05) lower in type 1 alcoholics (0.74+/-0.14 ml/ml) than in controls (0.89+/-0.14 ml/ml). In alcoholics, there was no normal left-to-right asymmetry of the temporal cortical heterogeneity of epidepride distribution observed in control males (0.89+/-0.19 vs. 1.10+/-0.19; P<0.05). The results suggest that the specific binding of dopamine D(2)/D(3) receptors in late type 1 alcoholics is decreased and its laterality in the temporal brain is altered from normal.

Z-IQNP: a potential radioligand for SPECT imaging of muscarinic acetylcholine receptors in Alzheimer's disease.

RATIONALE: The density of the M2 subtype of muscarinic acetylcholine receptors (mAChR) has been shown to be reduced in the brain of patients with Alzheimer's disease (AD). It is therefore of interest to develop a brain imaging method for diagnostic purposes. Z-(R,R)-1-azabicyclo[2.2.2]oct-3-yl alpha-hydroxy-alpha-(1-iodo1-propen-3-yl)-alpha-phenylacetat e (Z-IQNP) is a muscarinic antagonist with high affinity for the M2 subtype. OBJECTIVE: The pharmacological characteristics and topographic distribution of radiolabelled Z-IQNP as a radioligand for the M2 mAChR subtype were examined in vitro and in vivo. METHODS: Z-IQNP was labelled with 1251 and 123I. Autoradiography was performed on whole-hemisphere cryosections from human post mortem brains. SPECT was performed in a cynomolgus monkey. RESULTS: Autoradiography showed binding of [125I]Z-IQNP in all brain regions, which was inhibited by the non-selective muscarinic antagonist scopolamine. The addition of BIBN 99, a compound with high affinity for the M2 subtype, inhibited [125I]Z-IQNP binding particularly in the cerebellum, which has a high density of the M2 subtype. SPECT demonstrated high uptake of [123I]Z-IQNP in all brain regions. The binding was markedly reduced in all brain regions after pretreatment with the non-selective muscarinic antagonist dexetimide and also the M1 antagonist biperiden. Dexetimide markedly inhibited [123I]Z-IQNP binding in the cerebellum, which is consistent with a high density of M2-receptors in this region. The sigma receptor binding compound DuP 734 had no effect on Z-IQNP binding either in vitro or in vivo. CONCLUSIONS: This study indicates that radiolabelled Z-IQNP has high specificity for mAChR with higher affinity for the M2 than the M1 subtype and negligible affinity for sigma recognition sites both in vitro and in vivo. [123I]Z-IQNP should be useful for future SPECT studies in AD for examination of the density of M2 receptors particularly in the cerebellum.

Metabolism of [123I]epidepride may affect brain dopamine D2 receptor imaging with single-photon emission tomography.

Iodine-123 labelled epidepride is a novel radiopharmaceutical for the study of cerebral dopamine D2 receptors using single-photon emission tomography (SPET). A lipophilic labelled metabolite of [123I]epidepride which may enter the brain and hamper the quantitation of receptors has been observed in human plasma. In the present study, gradient high-performance liquid chromatography (HPLC) was used to investigate the plasma concentration of the lipophilic labelled metabolite and its correlation to SPET imaging of striatal dopamine D2 receptors. A linear regression fit showed a negative correlation between the amount of the lipophilic labelled metabolite and the striatum to cerebellum ratio (n=16, R=-0.58, P<0.02), suggesting that plasma metabolite analysis is essential when imaging dopamine D2 receptors with SPET using [123I]epidepride.

Iodine-123 labelled Z-(R,R)-IQNP: a potential radioligand for visualization of M(1 )and M(2) muscarinic acetylcholine receptors in Alzheimer's disease.

Z-(R)-1-Azabicyclo[2.2.2]oct-3-yl (R)-alpha-hydroxy-alpha-(1-iodo-1-propen-3-yl)-alpha-phenylacetate (Z-IQNP) has high affinity to the M(1 )and M(2) muscarinic acetylcholine receptor (mAChR) subtypes according to previous in vitro and in vivo studies in rats. In the present study iodine-123 labelled Z-IQNP was prepared for in vivo single-photon emission tomography (SPET) studies in cynomolgus monkeys. SPET studies with Z-[(123)I]IQNP demonstrated high accumulation in monkey brain (>5% of injected dose at 70 min p.i.) and marked accumulation in brain regions such as the thalamus, the neocortex, the striatum and the cerebellum. Pretreatment with the non-selective mAChR antagonist scopolamine (0.2 mg/kg) inhibited Z-[(123)I]IQNP binding in all these regions. The percentage of unchanged Z-[(123)I]IQNP measured in plasma was less than 10% at 10 min after injection, which may be due to rapid hydrolysis, as has been demonstrated previously with the E-isomer of IQNP. Z-[(123)I]IQNP showed higher uptake in M(2)-rich regions, compared with previously obtained results with E-[(123)I]IQNP. In conclusion, the radioactivity distribution from Z-[(123)I]IQNP in monkey brain indicates that Z-[(123)I]IQNP binds to the M(1)- and M(2)-rich areas and provides a high signal for specific binding, and is thus a potential ligand for mAChR imaging with SPET.

Iodine-123 labelled PE2I for dopamine transporter imaging: influence of age in healthy subjects.

The iodine-123 labelled selective ligand N-(3-iodoprop-2E-enyl)-2beta-carbomethoxy-3beta-(4-methylphe nyl)nortr opane ([(123)I]PE2I) has been developed and has been shown to be suitable for single-photon emission tomography imaging of the dopamine transporter. In this study the influence of age on ligand binding was investigated in 16 healthy males with an age range of 23- 75 years. Single-photon emission tomography (SPET) imaging was performed with a triple-headed gamma camera. A simplified reference region model, in which the input function was derived from the non-displaceable cerebellar compartment, was used to calculate the volume of distribution in the striatum. The volume of distribution was shown to decline with age (-0.4%/year; P<0.005). The results were in agreement with in vivo and in vitro findings of a decline in dopamine transporter binding with age. The findings confirm the suitability of [(123)I]PE2I for SPET imaging in clinical routine but emphasize the necessity of using age-matched controls in patient studies.

Effect of radiochemical purity of 99Tcm-Q12 on myocardial SPET image quality.

In myocardial perfusion SPET studies with 99Tcm-Q12, we observed that some patients had high liver uptake that interfered significantly in the assessment of the inferior wall. The aim of this study was to assess the effects of the radiochemical purity of 99Tcm-Q12 on liver uptake. Thirty-one patients undergoing routine myocardial infarction perfusion studies were evaluated. The radiochemical purity of 99Tcm-Q12 was determined using HPLC. Venous blood samples taken 50 min after injection of 99Tcm-Q12 during peak exercise were also analysed. Liver uptake was expressed as the liver-to-heart ratio. In addition, the SPET images were classified by two experienced nuclear medicine specialists into three groups representing high-quality images (n = 7), images with high general background activity (n = 13) and images with high liver and/or intestinal uptake (n = 11). The liver-to-heart ratio correlated inversely with the radiochemical purity of 99Tcm-Q12 (r = -0.65, P < 0.001) and unchanged 99Tcm-Q12 in plasma (r = -0.44, P < 0.02). The radiochemical purity of 99Tcm-Q12 was significantly lower in the group with high liver uptake (60.1 +/- 4.2%) than in the group with good-quality images (81.8 +/- 5.6%, P < 0.01) or with high background activity (82.3 +/- 2.5%, P < 0.01). In conclusion, the radiochemical purity of 99Tcm-Q12 has a significant inverse correlation with the liver-to-heart ratio; thus, the high radiochemical purity of 99Tcm-Q12 should be confirmed to prevent interference by liver uptake.

Evaluation of skiing injuries by Injury Severity Score.

The goal of this study was to evaluate the Injury Severity Score (ISS) in an alpine area. Hafjell Alpine Centre was the 1994 Winter Olympic Alpine arena in Lillehammer. A total of 2,044,484 lift transportations and 183 injuries were registered in the two winter seasons 1991 and 1992. The injury rate was 1.8 injuries per 1000 skier days. The mean ISS was 3.6 per injury for this particular alpine area. Thirty-six per cent of the injured were women and 35.5% were between 15 and 19 years of age. There was no difference in mean ISS between male and female skiers, but mean ISS was higher in adolescents than in the other age groups. Injuries to the knee represented the single most frequently injured body region, but injuries to the abdomen had the highest mean ISS. Alpine skiers suffered more severe injuries than telemark and snowboard skiers. Severe injuries (ISS > 16) were recorded when unexpected objects, such as a grooming machine, a net, a root, etc., appeared on the slope. The Abbreviated Injury Scale (AIS) and ISS give us additional information about the condition of the slopes, and their use as a tool in preventing skiing injuries is recommended.

Dopamine transporter and D2-receptor density in late-onset alcoholism.

RATIONALE: Late onset type 1 alcoholism has been suggested to be associated with an underlying dopaminergic defect. Therefore, it is relevant to study both postsynaptic D2-receptor and presynaptic dopamine transporter (DAT) densities among alcoholics. OBJECTIVE: We investigated DAT densities, along with striatal and extrastriatal dopamine D2-receptor densities, in nine nonviolent late-onset male alcoholics, who had no major mental disorder nor antisocial personality disorder (ASPD), and nine healthy controls. METHODS: [123I]PE2I and [123I]epidepride were used in SPECT imaging. RESULTS: DAT occupancy ratios (striatum/cerebellum) were significantly lower among alcoholics than in controls. Extrastriatal D2-receptor occupancy ratios (temporal pole/cerebellum) were not significantly different between the groups. CONCLUSIONS: Striatal presynaptic DAT densities are decreased among type 1 alcoholics, and this finding is not associated with recent alcohol abuse.

Comparison of HPLC, TLC and minicolumn for measuring the radiochemical purity of 99Tcm-Q12.

TechneScan Q12 (99Tcm-Q12) is a new agent for clinical myocardial perfusion imaging. A product with high radiochemical purity is essential for high-quality imaging. We compared three methods of radiochemical purity analysis for 99Tcm-Q12: thin-layer chromatography (TLC), high-performance liquid chromatography (HPLC) and minicolumn. Thin-layer chromatography resulted in lower purity (87 +/- 8%) than the minicolumn method (aluminium oxide minicolumn, ethanol) (95 +/- 4%). The HPLC method resulted in the lowest purity (79 +/- 11%). The main impurity was a polar compound, but three further impurities were found using HPLC. Using HPLC, we found the percentage of the parent compound (99Tcm-Q12) in plasma at 40-90 min post-injection to be 19.3 +/- 6.2%. We suggest that gradient HPLC is the most effective method for the analysis of the radiochemical purity of 99Tcm-Q12, and that it can be used to determine the concentration of 99Tcm-Q12 in plasma.

Abnormal structure of human striatal dopamine re-uptake sites in habitually violent alcoholic offenders: a fractal analysis.

Both animal and human studies imply that aggressive behaviour is associated with increased dopaminergic transmission. Our hypothesis was that impulsive violent offenders have also higher heterogeneity of the striatal dopamine transporter (DAT) density than controls. We performed a fractal analysis in 21 impulsive violent offenders, 10 non-violent alcoholics and 21 controls to measure the heterogeneity and laterality of the striatal DAT density characterised by [123I]beta-CIT single-photon emission tomography (SPET). The [123I]beta-CIT distribution was significantly more heterogeneous in the right striatum of violent offenders than in healthy controls. In addition, in young violent offenders there was no normal left-to-right asymmetry observed in control subjects of the same age. The normalisation of the left-to-right asymmetry may reflect late neurobiological maturation.

Fentanyl decreases beta-CIT binding to the dopamine transporter.

Evidence from animal studies suggest that centrally acting opiates increase synaptic dopamine (DA) concentration. However, the interaction between mu-opioid receptors and the DA system is unclear. We report here an effect of fentanyl on striatal [123I]beta-CIT binding to the DA transporter in a patient and in rats. A female patient underwent [123I]beta-CIT single-photon emission tomography (SPET) study after intrathecal injection of fentanyl for her back pain. After a 2-week drug-free period, the SPET study was repeated. In the experimental study, male Wistar rats were treated with fentanyl either acutely (50 micrograms/kg, i.p.) before imaging study or subacutely for 4 days (10 micrograms/kg, twice a day, i.p.). Brain planar imaging was performed at 3.5 hours after an intravenous injection of [123I]beta-CIT with gamma camera with a pinhole collimator. In a female patient, [123I]beta-CIT binding in the basal ganglia was decreased by 37% during fentanyl as compared to the binding after 2-week drug-free period. Similarly in rats, acute fentanyl treatment decreased [123I]beta-CIT binding to the striatum by 30% as compared to that of with the control rats. After subacute administration of fentanyl, no significant difference was observed compared to the control group. According to the present data, fentanyl decreases [123I]beta-CIT binding in the basal ganglia both in human and rats, suggesting that opiates possibly directly affect DA reuptake.