Low-frequency Trains Research Articles

Enhanced D1 and D2 inhibitions induced by low-frequency trains of conditioning stimuli: differential effects on H- and T-reflexes and possible mechanisms.

Mechanically evoked reflexes have been postulated to be less sensitive to presynaptic inhibition (PSI) than the H-reflex. This has implications on investigations of spinal cord neurophysiology that are based on the T-reflex. Preceding studies have shown an enhanced effect of PSI on the H-reflex when a train of ~10 conditioning stimuli at 1 Hz was applied to the nerve of the antagonist muscle. The main questions to be addressed in the present study are if indeed T-reflexes are less sensitive to PSI and whether (and to what extent and by what possible mechanisms) the effect of low frequency conditioning, found previously for the H-reflex, can be reproduced on T-reflexes from the soleus muscle. We explored two different conditioning-to-test (C-T) intervals: 15 and 100 ms (corresponding to D1 and D2 inhibitions, respectively). Test stimuli consisted of either electrical pulses applied to the posterior tibial nerve to elicit H-reflexes or mechanical percussion to the Achilles tendon to elicit T-reflexes. The 1 Hz train of conditioning electrical stimuli delivered to the common peroneal nerve induced a stronger effect of PSI as compared to a single conditioning pulse, for both reflexes (T and H), regardless of C-T-intervals. Moreover, the conditioning train of pulses (with respect to a single conditioning pulse) was proportionally more effective for T-reflexes as compared to H-reflexes (irrespective of the C-T interval), which might be associated with the differential contingent of Ia afferents activated by mechanical and electrical test stimuli. A conceivable explanation for the enhanced PSI effect in response to a train of stimuli is the occurrence of homosynaptic depression at synapses on inhibitory interneurons interposed within the PSI pathway. The present results add to the discussion of the sensitivity of the stretch reflex pathway to PSI and its functional role.

Hippocampal metaplasticity is required for the formation of temporal associative memories.

Metaplasticity regulates the threshold for modification of synaptic strength and is an important regulator of learning rules; however, it is not known whether these cellular mechanisms for homeostatic regulation of synapses contribute to particular forms of learning. Conditional ablation of mGluR5 in CA1 pyramidal neurons resulted in the inability of low-frequency trains of afferent activation to prime synapses for subsequent theta burst potentiation. Priming-induced metaplasticity requires mGluR5-mediated mobilization of endocannabinoids during the priming train to induce long-term depression of inhibition (I-LTD). Mice lacking priming-induced plasticity had no deficit in spatial reference memory tasks, but were impaired in an associative task with a temporal component. Conversely, enhancing endocannabinoid signaling facilitated temporal associative memory acquisition and, after training animals in these tasks, ex vivo I-LTD was partially occluded and theta burst LTP was enhanced. Together, these results suggest a link between metaplasticity mechanisms in the hippocampus and the formation of temporal associative memories.

Rewarding stimulation of the lateral hypothalamus induces a dopamine-dependent suppression of synaptic responses in the entorhinal cortex

The entorhinal cortex receives inputs from sensory and associational cortices, as well as a substantial input from midbrain dopaminergic neurons. Dopamine is likely to modulate the responsiveness of entorhinal cortex neurons to sensory inputs, and excitatory synaptic responses in layers I/II of the entorhinal cortex in vitro can be either facilitated or suppressed by dopamine depending upon the concentration applied. Rewarding stimulation of the lateral hypothalamus leads to activation of dopamine neurons, and the present study evaluated the effect of rewarding stimulation on synaptic responses in the lateral entorhinal cortex evoked by stimulation of the primary olfactory (piriform) cortex in behaving rats. Rewarding brain stimulation reduced the amplitude of synaptic responses in the entorhinal cortex evoked by single pulses delivered to the piriform cortex at intervals of 100–500ms following the train. Synaptic responses were suppressed when stimulation trains were delivered at a fixed interval, or when trains were initiated by the animal pressing a bar. The suppression depended on the strength of stimulation trains; delivery of higher frequency trains that were sufficient to induce maximal, or 50% of maximal, rates of bar-pressing resulted in significant suppression effects, but lower frequency trains did not. Systemic administration of the dopamine D2 receptor antagonist eticlopride, but not the D1 receptor antagonist SCH23390 or the muscarinic antagonist scopolamine, blocked the suppression of synaptic responses. Results suggest that rewarding brain stimulation leads to a phasic increase in dopamine in the entorhinal cortex resulting in a D2 receptor-dependent suppression of excitatory synaptic responses, and that a similar synaptic modulation may be induced by stimuli associated with appetitive motivation and reward.

The analgesic effect of electroacupuncture on inflammatory pain in the rat model of collagenase-induced arthritis: mediation by opioidergic receptors

Electroacupuncture (EA) is widely practiced for the treatment of osteoarthritic (OA) pain, but its therapeutic mechanisms have not yet been fully studied, especially in the experimental OA rat model. In order to induce collagenase-induced arthritis (CIA) in rats, male Sprague-Dawley rats were intra-articularly injected with 0.05 ml of 4 mg/ml collagenase solution in the left knee of the hind limb, followed by a booster injection 4 days later. Maximal gross, histopathological features and biomarker activity changes consistent with human OA characteristics were observed four weeks after the first collagenase injection. In the exploratory preliminary study of EA stimulation parameters, low-frequency train pulse EA stimulation (2 Hz, 0.07 mA, 0.3 ms) delivered to the Zusanli (ST36) acupoint exerted an antinociceptive effect with acupoint specificity in a rat model of CIA. The antinociceptive effect of Zusanli EA was blocked by intraperitoneal pretreatment with naloxone (μ-opioid receptor antagonist, 2 mg/kg) and naltrindole (δ-opioid receptor antagonist, 1 mg/kg), but not with norbinaltophimine (κ-opioid receptor antagonist, 20 mg/kg). The synergistic antinociceptive effects of Zusanli EA were achieved with statistical significance by i.p. pretreatment with DAMGO (μ-opioid receptor agonist, 1 mg/kg) and with [D-Ala2]-Deltorphin II (δ-opioid receptor agonist, 6 mg/kg), but not with (±)-U-50488 (κ-opioid receptor agonist, 3 mg/kg). These results suggest that the 2-Hz EA can attenuate the osteoarthritic pain in CIA, and the analgesic effects of EA can be mediated by μ-opioid and δ-opioid, but not by κ-opioid receptors.

Extracellular Alpha-Synuclein Oligomers Modulate Synaptic Transmission and Impair LTP Via NMDA-Receptor Activation

Parkinson's disease (PD) is the most common representative of a group of disorders known as synucleinopathies, in which misfolding and aggregation of α-synuclein (a-syn) in various brain regions is the major pathological hallmark. Indeed, the motor symptoms in PD are caused by a heterogeneous degeneration of brain neurons not only in substantia nigra pars compacta but also in other extrastriatal areas of the brain. In addition to the well known motor dysfunction in PD patients, cognitive deficits and memory impairment are also an important part of the disorder, probably due to disruption of synaptic transmission and plasticity in extrastriatal areas, including the hippocampus. Here, we investigated the impact of a-syn aggregation on AMPA and NMDA receptor-mediated rat hippocampal (CA3-CA1) synaptic transmission and long-term potentiation (LTP), the neurophysiological basis for learning and memory. Our data show that prolonged exposure to a-syn oligomers, but not monomers or fibrils, increases basal synaptic transmission through NMDA receptor activation, triggering enhanced contribution of calcium-permeable AMPA receptors. Slices treated with a-syn oligomers were unable to respond with further potentiation to theta-burst stimulation, leading to impaired LTP. Prior delivery of a low-frequency train reinstated the ability to express LTP, implying that exposure to a-syn oligomers drives the increase of glutamatergic synaptic transmission, preventing further potentiation by physiological stimuli. Our novel findings provide mechanistic insight on how a-syn oligomers may trigger neuronal dysfunction and toxicity in PD and other synucleinopathies.

운동빈도의 차이가 식이유도 운동알레르기 질환과 관련기전에 미치는 영향

본 연구에서는 적절하게 알레르기가 유발되는 운동강도인 50분간의 강도를 선정한 후 운동빈도를 서로 달리하여 통제 그룹(S) 저빈도 그룹(F2, 주2회), 중빈도 그룹(F3, 주 3회) 및 고빈도 그룹(F5, 주5회)으로 나누어 훈련을 부여하고 OVA알부민으로 감작한 후 OVA로 challenge를 하였을 때, 알레르기 아나플락시스의 변화 양상 차이를 살펴보고 동시에 기전변화를 함께 규명하고자 하였다. 본 연구를 위해 그룹당 25마리씩 통제군(S; control sensitized, n=25), 저빈도 훈련군(F2, n=25), 중빈도 훈련군(F3, n=25) 및 고빈도 훈련군(F5, n=25)으로 구분하여 수영훈련 빈도에 따른 알레르기를 유도하였을 때, 알레르기 아나플락시스를 조사하고 아울러 비장지수, 림프구의 수, 복강 ROS, ASAS, 및 싸이토카인(INF-<TEX>${\gamma}$</TEX>, IL-4)의 변화를 함께 측정하였다. 이 때, 알러지 아나플락시스 테스트는 그룹당 10마리를 사용하였고, 나머지는 세포분석과 ROS 측정을 위하여 사용하였다. 본 연구결과 일반 감작군에 비하여 운동 감작군에서 알러지가 더 잘 유도됨을 알 수 있었고, 같은 운동강도 부여시 저빈도의 운동군에 비하여 고빈도 운동군에서 알러지 반응이 더 잘 일어남을 확인 할 수 있었다. 이는 고빈도 운동군에서 현저히 증가되는 IL-4 반응과 ASAS 반응으로 알 수 있었고, 특히 이러한 반응이 고빈도 운동그룹에서 현저히 증가하는 ROS 반응과 일치함을 확인하였다. 한편 저빈도 그룹에서는 오히려 INF-<TEX>${\gamma}$</TEX>의 증가와 ROS 반응이 감소하였고, ASAS 반응이 통제군보다 오히려 줄어들어 운동의 빈도가 알레르기반응과 밀접한 연관이 있음을 확인할 수 있었다. 추후 이러한 원인에 대한 면밀한 분석이 요구되며, 알레르기 반응의 cross training 및 detraining 효과도 함께 규명 되어야 할 것으로 여겨진다. Food allergies have become a serious health concern in the past two decades, especially in developed countries. Foods associated with allergies include vegetables, some fruits, shellfish, wheat, egg, chicken, and nuts. To describe the specific fundamentals, etiological factors, and clinical manifestations, we analyzed the different physical frequency on spleen index in sensitized and regular exercise-trained mice. We also conducted a proliferation assay of lymphocytes to OVA, ROS, ASAS, and we determined the cytokine levels. Female BALB/c mice were bred in the animal laboratory of the P and D university under controlled conditions (<TEX>$22{\pm}2^{\circ}C$</TEX>, RH 45-55%, and a 12-hour photoperiod). The animals were 6 weeks old at the start of the study and were fed a standard commercial chow diet from 09:00 to 15:00 for the 8-week study period. All animals had access to distilled deionized water ad libitum. They were divided into four groups: a control group (S; control sensitized, n=25), a low-frequency training group (F2, n=25), a mid-frequency training group (F3, n=25), and a high-frequency training group (F5, n=25) following the treatment of exercise time per week. The results were as follows: The mice spleen index showed the highest grade in the F5 group compared with the other groups; this level showed in an exercise frequency-dependent manner. In the proliferation assay of OVA, the F5 group showed the highest grade compared with the other groups; this level was also showed in an exercise frequency-dependent manner. Peritoneal ROS and ASAS showed a statistically significant increase in the F5 group and decreased in the F2 group compared with the S group. However, there were no significant differences in the F3 group. The highest level of IL-4 was found in the F5 group compared with the other groups. However, the highest level of INF-<TEX>${\gamma}$</TEX> was in the F2 group. The results suggest that FDEIA is positively correlated with the frequency of exercise due to the direct effect of physical exercise on peritoneal ROS and the cytokine profile. Further research is needed on the specific mechanism underlying the combined effects of exercise intensity and frequency on physical-induced allergy anaphylaxis.

Voltage-Dependent Calcium Channels at the Plasma Membrane, but Not Vesicular Channels, Couple Exocytosis to Endocytosis

Although calcium influx triggers endocytosis at many synapses and non-neuronal secretory cells, the identity of the calcium channel is unclear. The plasma membrane voltage-dependent calcium channel (VDCC) is a candidate, and it was recently proposed that exocytosis transiently inserts vesicular calcium channels at the plasma membrane, thus triggering endocytosis and coupling it to exocytosis, a mechanism suggested to be conserved from sea urchin to human. Here, we report that the vesicular membrane, when inserted into the plasma membrane upon exocytosis, does not generate a calcium current or calcium increase at a mammalian nerve terminal. Instead, VDCCs at the plasma membrane, including the P/Q-type, provide the calcium influx to trigger rapid and slow endocytosis and, thus, couple endocytosis to exocytosis. These findings call for reconsideration of the vesicular calcium channel hypothesis. They are likely to apply to many synapses and non-neuronal cells in which VDCCs control exocytosis, and exocytosis is coupled to endocytosis.

Physiological Demands of Therapeutic Horseback Riding in Children With Moderate to Severe Motor Impairments

To examine energy expenditure at rest and during a single therapeutic horseback riding (THR) session in children with moderate to severe motor impairments. Heart rate (HR), oxygen uptake (.VO2), and minute ventilation (.VE) were measured continuously during a 10-minute rest period and during a typical THR session. Seven children (4 males, mean age 12.3 ± 3.5 years) completed the protocol. Significant increases from rest were seen for mean HR, .VO2, .VE, and energy expenditure. Based on .VO2, 43.3 ± 24.3% of the THR session consisted of sedentary, 44.4 ± 13.4% of light, and 12.3 ± 21.8% of moderate to vigorous activity intensity, with large interindividual differences. The physiological demands of THR in children with moderate to severe motor impairments are moderate. However, considering the short duration of maintaining moderate to vigorous exercise activity during THR in combination with the low training frequency, group data indicate that it is unlikely that THR will improve cardiopulmonary fitness in these children.

GABA-A receptors play a minor role in cortical epileptic afterdischarges in immature rats

The role of inhibitory γ-aminobutyric acid-A (GABA-A) system in the cortical epileptic afterdischarges (ADs) was studied at three different developmental stages of rats. Animals 12, 18 and 25 days old with implanted epidural electrodes were pretreated with bicuculline (1 and 2 mg/kg i.p.) and 15 min later repeatedly stimulated with low frequency trains with stepwise increasing current intensity. Bicuculline only exceptionally decreased threshold current intensities necessary for elicitation of movements directly bound to stimulation, spike-and wave ADs, clonic seizures and transition into a limbic type of ADs. Duration of ADs was not systematically affected by either dose of bicuculline. In contrast, transcallosal evoked potentials exhibited under the influence of bicuculline steeper curve expressing relation between intensity of stimuli and amplitude of responses. In contrast to GABA-B receptors, GABA-A receptors do not play an important role in generation and arrest of cortical epileptic ADs in immature rats.

Atypical properties of release and short-term depression at a specialized nicotinic synapse in the Mauthner cell network

Many synapses exhibit temporally complex forms of activity-dependent short-term synaptic plasticity. The diversity of these phenomena reflects the evolutionary specialization of synapses within networks. We examined the properties of transmission and plasticity, in vivo, at an identified, specialized axo-axonic nicotinic synapse between the goldfish Mauthner cell and one of its targets, the cranial relay neuron (CRN), using intracellular paired recordings and low frequency (0.33-2 Hz) train stimulations. Depression of successive excitatory postsynaptic potentials (EPSPs), which dominates short-term plasticity, had two components. A fast component reduced the amplitude of EPSP(2), to less than 50% of EPSP(1). A slow component produced an additional 10-30% of amplitude reduction and developed with a time constant of tens of seconds. The latencies of the later depressed responses were ∼0.1 ms longer than that of EPSP(1), suggesting a reduced release probability. The Ca(2+) chelators EGTA and BAPTA, injected presynaptically, reduced all EPSPs and slowed development of the second component of depression. Interestingly, spike broadening, produced by injecting K(+) channel blockers, reduced release, but accelerated the kinetics of the slow component. Finally, Ba(2+) in the external medium enhanced release, and reduced the first component and slowed the development of the second component of depression. Taken together, these last two results, which are in contrast to observations at other synapses, and the two-component depression suggest atypical release properties at the output synapses of the Mauthner cell, which triggers an escape behavior. We suggest that the second component of depression provides an additional safety factor to prevent repetitive firing of the CRN.

Hypoxia inducible factor 1α links fast‐patterned muscle activity and fast muscle phenotype in rats

Exercise influences muscle phenotype by the specific pattern of action potentials delivered to the muscle, triggering intracellular signalling pathways. PO2 can be reduced by an order of magnitude in working muscle. In humans, carriers of a hyperactive polymorphism of the transcription factor hypoxia inducible factor 1α (HIF-1α) have 50% more fast fibres, and this polymorphism is prevalent among strength athletes. We have investigated the putative role of HIF-1α in mediating activity changes in muscle.When rat muscles were stimulated with short high frequency bursts of action potentials known to induce a fast muscle phenotype, HIF-1α increased by about 80%. In contrast, a pattern consisting of long low frequency trains known to make fast muscles slow reduced the HIF-1α level of the fast extensor digitorum longus (EDL) muscle by 44%. Nuclear protein extracts from normal EDL contained 2.3-fold more HIF-1α and 4-fold more HIF-1β than the slow soleus muscle, while von-Hippel-Lindau protein was 4.8-fold higher in slow muscles. mRNA displayed a reciprocal pattern; thus FIH-1 mRNA was almost 2-fold higher in fast muscle, while the HIF-1α level was half, and consequently protein/mRNA ratio for HIF-1α was more than 4-fold higher in the fast muscle, suggesting that HIF-1α is strongly suppressed post-transcriptionally in slow muscles.When HIF-1α was overexpressed for 14 days after somatic gene transfer in adult rats, a slow-to-fast transformation was observed, encompassing an increase in fibre cross sectional area, oxidative enzyme activity and myosin heavy chain. The latter was shown to be regulated at the mRNA level in C2C12 myotubes.

Effect of Endurance Exercise on Resting Testosterone Levels in Sedentary Subjects

To investigate the effects of moderate-intensity and low frequency exercise on resting serum testosterone and cortisol levels, resting heart rate, and isokinetic strength among healthy sedentary young men. A randomized controlled study. Forty sedentary young men aged 18 to 25 years old, pedaled 50 minutes on a bicycle ergometry at 60% of maximal effort once a week for 12 weeks in an exercise group. Resting total and free serum testosterone, serum cortisol, anthropometric data, resting heart rate, and isokinetic strength during shoulder and knee extensions. Resting serum total and free testosterone, as well as cortisol did not differ significantly between groups. Neither group showed any significant changes in anthropometric data and isokinetic strength at the end of study. However, the resting heart rate of the exercise group reduced significantly after the training (p < 0.05). Also, the isokinetic strength of shoulder and knee significantly increased (p < 0.05). Twelve weeks of moderate-intensity and low frequency training had no effect on resting serum testosterone, but were sufficient to increase aerobic fitness among sedentary young men. The type of exercise training may encourage sedentary individuals to participate regularly in the program on physical activity.

Neuromodulation by GABA Converts a Relay Into a Coincidence Detector

Modulation of synaptic strength by γ-aminobutyric acid receptors (GABARs) is a common feature in sensory pathways that contain relay cell types. However, the functional impact of these receptors on information processing is not clear. We considered this issue at bushy cells (BCs) in the cochlear nucleus, which relay auditory nerve (AN) activity to higher centers. BCs express GABA(A)Rs, and synaptic inputs to BCs express GABA(B)Rs. We tested the effects of GABAR activation on the relaying of AN activity using patch-clamp recordings in mature mouse brain slices at 34°C. GABA affected BC firing in response to trains of AN activity at concentrations as low as 10 μM. GABA(A)Rs reduced firing primarily late in high-frequency trains, whereas GABA(B)Rs reduced firing early and in low-frequency trains. BC firing was significantly restored when two converging AN inputs were activated simultaneously, with maximal effect over a window of <0.5 ms. Thus GABA could adjust the function of BCs, to suppress the relaying of individual inputs and require coincident activity of multiple inputs.

Correspondence

To the Editor: RE: ‘Functional characteristics of the rat jaw muscles: daily muscle activity and fiber type composition’ by Kawai et al. Journal of Anatomy, Vol. 215, pp. 656–662. Kawai et al. present an interesting study of the relationship between electromyographic activity in jaw muscles and their fibre type composition (Kawai et al. 2009). The concept of functional adaptation has been widely accepted since I introduced it in the 1970s (Salmons & Sréter, 1976; Salmons, 1980; Salmons & Henriksson, 1981). The evidence comes entirely from muscles of the limbs and trunk, but it is reasonable to expect the same regulatory phenomena to be present in skeletal muscles of cranial origin even though they contain, and often co-express, a greater diversity of myosin heavy chain isoforms. The authors of this paper appear, however, to have misinterpreted the adaptive hypothesis. This states that sustained high levels of activity induce slow, fatigue-resistant properties; low or intermittent levels of activity allow the fibers to retain, or revert to, a native fast, fatigue-susceptible state. Accordingly, where there is a high proportion of type IIX fibres it would be associated not with the generation of large forces, as the authors propose, but with a low aggregate amount of activity. The high-frequency patterns needed to produce large forces do not differ from low-frequency patterns in their effect on myosin isoform composition (Hudlicka et al. 1982; Kernell et al. 1987; Sutherland et al. 2003). It is certainly true that the muscles of smaller animals have a lower proportion of slow fibres. This is associated with a higher threshold for the transition from fast to slow myosin isoforms (Salmons & Henriksson, 1981; Sutherland et al. 1998, 2006). The transition, although present in the rat, is correspondingly more difficult to demonstrate than in larger species (Jarvis et al. 1996). On this basis a better correlation between the proportion of type I fibres and muscle activity should be seen in a larger experimental animal, and has in fact been found in rabbit jaw muscles by van Wessel et al. (2005). This citation is curiously absent from the present paper. There is a good deal of published evidence to show that myosin heavy chain composition responds to the aggregate number of impulses reaching the muscle (see Salmons, 2009 for a recent review). Unfortunately this is not measured by the overall duration and amplitude of electromyographic activity over the same period: high-frequency bursts of short duration could deliver the same number of impulses as low-frequency trains of longer duration. If the authors were able to take this into account, the apparent inconsistencies in their data for the anterior temporalis muscle and the seeming departures from Henneman’s size principle would, I suggest, disappear.

Interaction between facilitation and depression at a large CNS synapse reveals mechanisms of short-term plasticity.

The two fundamental forms of short-term plasticity, short-term depression and facilitation, coexist at most synapses, but little is known about their interaction. Here, we studied the interplay between short-term depression and facilitation at calyx of Held synapses. Stimulation at a "low" frequency of 10 or 20 Hz, which is in the range of the spontaneous activity of these auditory neurons in vivo, induced synaptic depression. Surprisingly, an instantaneous increase of the stimulation frequency to 100 or 200 Hz following the low-frequency train uncovered a robust facilitation of EPSCs relative to the predepressed amplitude level. This facilitation decayed rapidly ( approximately 30 ms) and depended on presynaptic residual Ca(2+), but it was not caused by Ca(2+) current facilitation. To probe the release probability of the remaining readily releasable vesicles following the low-frequency train we made presynaptic Ca(2+) uncaging experiments in the predepressed state of the synapse. We found that low-frequency stimulation depletes the fast-releasable vesicle pool (FRP) down to approximately 40% of control and that the remaining FRP vesicles are released with approximately 2-fold slower release kinetics, indicating a hitherto unknown intrinsic heterogeneity among FRP vesicles. Thus, vesicles with an intrinsically lower release probability predominate after low frequency stimulation and undergo facilitation during the onset of subsequent high-frequency trains. Facilitation in the predepressed state of the synapse might help to stabilize the amount of transmitter release at the onset of high-frequency firing at these auditory synapses.

Utstyr, laboratorieanalyser og medikamenter ved kommunale legevakter

Availability of equipment for diagnostics and treatment in out-of-hours services in Norway is not documented and no guidelines exist on requirements for the various types of equipment (including drugs) needed. A knowledge basis on status and needs should be established so minimum requirements can be developed.The National Centre for Emergency Primary Health Care sent a questionnaire on availability of diagnostic equipment, laboratory tests, medication and quality assurance systems to all 261 municipal out-of-hours services in Norway in February 2006.223/261 (86 %) of the services responded. 150 used the same office as a day-time practice, 59 had their own office and 14 were localised in a hospital/ emergency care unit. Services located in GP surgeries with a daytime-practice had a wider range of equipment, laboratory tests and medicines. Physicians on duty in the out-of-hours services with shared facilities did much of the laboratory work, but the quality control was done by the personnel at daytime. 27 % of the independent services did not have external control of their laboratory work (they were not members of the Norwegian Quality Improvement of Primary Care Laboratories). GPs were trained on acute medical situations more than once a year in 52 % of all the out-of-hours-services, but for only 40 % in the independent services. Other personnel were trained more than once a year in 74 % of the independent services.Availability of equipment and laboratory test repertoire for GPs on duty at out-of-hours services seems to depend on whether the services are shared with GP surgeries and also used at daytime, and the distance to ambulance, hospital and pharmacy. Lack of routines for laboratory work and low training frequency in acute medical procedures may lead to poor quality of the analyses and lower competence than needed.

The Need for Advanced Public Transport Information Services When Making Transfers

This paper reports on a stated choice experiment examining the determinants of travelers' need and willingness to pay for advanced public transport information services. Specific attention is given to the role of making transfers in the decision to acquire specific types of information. Intercity train travelers are asked to choose among information services that varied in type of information provided by the services, precision of provided dynamic travel time estimates, whether or not the system can provide information unasked for and price. Respondents made these choices conditional on a specified transfer context, denoting whether or not transfers had to be made during the trip, and whether these were transfers to high or low frequency train services. Modeling results indicate that as hypothesized, transferring during the trip, especially towards low frequency connections, induces a larger need for travel information, a higher preference for services that can provide advice relative to other information and a higher willingness to pay for information in general. However, the choice for information services is highly price sensitive, which suggest a low overall willingness to pay.

Repetitive transcranial magnetic stimulation in the treatment of epilepsia partialis continua

Repetitive transcranial magnetic stimulation (rTMS) is a technique for noninvasive focal brain stimulation by which small intracranial electrical currents are generated by a fluctuating extracranial magnetic field. In clinical epilepsy, rTMS has been applied most often interictally to reduce seizure frequency. Less often, rTMS has been used to terminate ongoing seizures, as in instances of epilepsia partialis continua (EPC). Whether ictal rTMS is effective and safe in the treatment of EPC has not been extensively studied. Here, we describe our recent experience with rTMS in the treatment of EPC, as an early step toward evaluating the safety and efficacy of rTMS in the treatment of intractable ongoing focal seizures. Seven patients with EPC of mixed etiologies were treated with rTMS applied over the seizure. rTMS was delivered in high-frequency (20-100 Hz) bursts or as prolonged low-frequency (1 Hz) trains. The EEG was recorded for three of the seven patients. rTMS resulted in a brief (20-30 min) pause in seizures in three of seven patients and a lasting (>or=1 day) pause in two of seven. A literature search identified six additional reports of EPC treated with rTMS where seizures were suppressed in three of six. Seizures were not exacerbated by rTMS in any patient. Generally mild side effects included transient head and limb pain, and limb stiffening during high-frequency rTMS trains. Our clinical observations in a small number of patients suggest that rTMS may be safe and effective in suppressing ongoing seizures associated with EPC. However, a controlled trial is needed to assess the safety and anticonvulsive efficacy of rTMS in the treatment of EPC.

112 THE EFFECT OF TRANSCUTANEOUS LASER BLOOD IRRADIATION UPON CMV/EBV INFECTION AND CHRONIC FATIGUE SYNDROME DEVELOPMENT

The present study examines the effects of auricular transcutaneous electrical nerve stimulation (TENS) on electrical pain threshold measured at the ipsilateral wrist and autonomie functions including skin temperature, blood pressure and pulse rate in 24 healthy subjects. TENS was administered as low frequency trains of pulses delivered at a ‘strong but comfortable’ intensity to 1 of 3 auricular points to be examined: 1.(i) autonomic effects (autonomie point),2.(ii) pain threshold effects (wrist point),3.(iii) placebo effects at an unrelated point (face point). A fourth untreated group was designated as a situation control. The main finding of the study was that auricular TENS produced no significant overall effects on experimental pain threshold or autonomic functions recorded under the present conditions. However, pain threshold was found to increase by over 50% of its pretreatment baseline in 4 subjects and by 30% in 6 subjects. This rise was not dependent upon the site of auricular TENS. The possible mechanisms of such changes are discussed.

Neuromuscular Adaptations to Low-Frequency Stimulation Training in a Patient with Chronic Heart Failure

Electrical myostimulation (EMS) has recently been proposed as an interesting rehabilitation tool in patients with chronic heart failure (CHF). Although its beneficial effects on exercise capacity and muscle strength have been demonstrated, the neuromuscular adaptations responsible for improved performance are not well understood. This preliminary case report was therefore planned to investigate the neural and muscular adaptations to a 5-wk EMS program in one patient. An increase in maximal strength (10.5%) was accompanied by increased twitch torque (13.9%) and slowing of muscle contractile properties (half-relaxation time, time to peak torque, and maximal rate of relaxation increased by 7.1, 31.1, and 16.6%, respectively) without changes in muscle activation. This preliminary case report therefore shows that in a highly deconditioned patient, EMS training improved strength through muscular adaptations rather than by neural changes, suggesting that EMS may be valuable for counterbalancing loss of muscle strength and function common in CHF patients.