前庭诱发肌源性电位结合纯音测听在大前庭水管综合征患者的临床应用

目的 通过记录、分析大前庭水管综合征（LVAS）患者的前庭诱发的肌源性电位(VEMP) 和纯音测听（PTA）状况,了解其球囊及前庭下神经功能和纯音听力特征,探讨其在LVAS患者的临床应用及意义。方法 对22例（42耳）LVAS患者行内耳高分辨率CT扫描、纯音测听和VEMP检查,对检查结果结合其临床症状进行总结、分析。结果 双侧短声刺激42患耳中25耳（占59.5%）VEMP表现为高振幅和（或）低阈值;42患耳纯音测听有30耳（占71.4%）表现为低中频（2KHz以下）存在明显气骨导差的混合性聋。VEMP低阈值组,前庭水管内径平均值为（4.30±0.53）mm,纯音听力低中频平均气骨导差值为（36±17）dB HL, 19耳主观听力易受外界原因或发热致颅内压改变而波动;VEMP非低阈值组前庭水管内径平均值为（2.80±0.67）mm,纯音听力低中频平均气骨导差值为（32±15）dB HL,4耳主观听力易受外界原因或发热致颅内压改变而波动。结论 VEMP阈值较低者,其前庭水管平均内径值较大,主观听力也易受外界原因或发热致颅内压增高的改变而波动。而纯音听力损失程度与前庭水管内径平均值无相关性,与VEMP振幅的大小及阈值的高低亦无相关性。     

Partial nerve injury induces electrophysiological changes in conducting (uninjured) nociceptive and nonnociceptive DRG neurons: Possible relationships to aspects of peripheral neuropathic pain and paresthesias

Partial nerve injury leads to peripheral neuropathic pain. This injury results in conducting/uninterrupted (also called uninjured) sensory fibres, conducting through the damaged nerve alongside axotomised/degenerating fibres. In rats seven days after L5 spinal nerve axotomy (SNA) or modified-SNA (added loose-ligation of L4 spinal nerve with neuroinflammation-inducing chromic-gut), we investigated a) neuropathic pain behaviours and b) electrophysiological changes in conducting/uninterrupted L4 dorsal root ganglion (DRG) neurons with receptive fields (called: L4-receptive-field-neurons). Compared to pretreatment, modified-SNA rats showed highly significant increases in spontaneous-foot-lifting duration, mechanical-hypersensitivity/allodynia, and heat-hypersensitivity/hyperalgesia, that were significantly greater than after SNA, especially spontaneous-foot-lifting. We recorded intracellularly in vivo from normal L4/L5 DRG neurons and ipsilateral L4-receptive-field-neurons. After SNA or modified-SNA, L4-receptive-field-neurons showed the following: a) increased percentages of C-, Ad-, and Ab-nociceptors and cutaneous Aa/b-low-threshold mechanoreceptors with ongoing/spontaneous firing; b) spontaneous firing in C-nociceptors that originated peripherally; this was at a faster rate in modified-SNA than SNA; c) decreased electrical thresholds in A-nociceptors after SNA; d) hyperpolarised membrane potentials in A-nociceptors and Aa/b-low-threshold-mechanoreceptors after SNA, but not C-nociceptors; e) decreased somatic action potential rise times in C- and A-nociceptors, not Aa/b-low-threshold-mechanoreceptors. We suggest that these changes in subtypes of conducting/uninterrupted neurons after partial nerve injury contribute to the different aspects of neuropathic pain as follows: spontaneous firing in nociceptors to ongoing/spontaneous pain; spontaneous firing in Aa/b-low-threshold-mechanoreceptors to dysesthesias/paresthesias; and lowered A-nociceptor electrical thresholds to A-nociceptor sensitization, and greater evoked pain.     

A high proportion of users of low-threshold facilities with needle exchange programmes in Switzerland are currently on methadone treatment: implications for new approaches in harm reduction and care

Background

Increasingly, patients receiving methadone treatment are found in low threshold facilities (LTF), which provide needle exchange programmes in Switzerland. This paper identifies the characteristics of LTF attendees receiving methadone treatment (MT) compared with other LTF attendees (non-MT).

Methods

A national cross-sectional survey was conducted in 2006 over five consecutive days in all LTF (n = 25). Attendees were given an anonymous questionnaire, collecting information on socio-demographic indicators, drug consumption, injection, methadone treatment, and self-reported HIV and HCV status. Univariate analysis and logistic regression were performed to compare MT to non-MT. The response rate was 66% (n = 1128).

Results

MT comprised 57.6% of the sample. In multivariate analysis, factors associated with being on MT were older age (OR: 1.38), being female (OR: 1.60), having one's own accommodation (OR: 1.56), receiving public assistance (OR: 2.29), lifetime injecting (OR: 2.26), HIV-positive status (OR: 2.00), and having consumed cocaine during the past month (OR: 1.37); MT were less likely to have consumed heroin in the past month (OR: 0.76, not significant) and visited LTF less often on a daily basis (OR: 0.59). The number of injections during the past week was not associated with MT.

Conclusions

More LTF attendees were in the MT group, bringing to light an underappreciated LTF clientele with specific needs. The MT group consumption profile may reflect therapeutic failure or deficits in treatment quality and it is necessary to acknowledge this and to strengthen the awareness of LTF personnel about potential needs of MT attendees to meet their therapeutic goals.     

Phenytoin partially antagonized L-type Ca2+ current in glucagon-secreting tumor cells (ITC-1)

Summary Transmembrane Ca²⁺ currents were investigated by means of a whole-cell clamp technique in a hamster glucagon-secreting tumor cell line (ITC-1). Two types of Ca²⁺ current were identified in ITC-1 cells. The low-threshold and transient (T-type) current became detectable above the potential level around –60 mV and decayed rapidly with an inactivation time constant of 95 ms (at –40 mV and 23°C), while the high-threshold and long-lasting (L-type) one was activated by depolarization more positive to –30 mV with non-inactivating kinetics. The voltage dependence and kinetics of these currents were identical to those reported in guinea-pig pancreatic ₂ cells. Both currents were augmented by equimolar substitution of Ca²⁺ with Ba²⁺ and completely abolished by adding 1 M La³⁺. Phenytoin, a well known anti-epileptic drug and a postulated T-type specific Ca²⁺ current antagonist, surprisingly blocked the L-type current without affecting the T-type current in ITC-1 cells. While phenytoin antagonized the L-type Ba²⁺ current selectively, 60% of the current remained even in supramaximal concentration range over 500 M. The residual component of the L-type current was completely abolished by adding nifedipine.     

Paracrine-like excitation of low-threshold mechanoceptive C-fibers innervating rat hairy skin is mediated by substance P via NK-1 receptors

We reported previously that C-fibers innervating rat skin can be excited by short trains of electrical shocks ('tetanus') applied to neighboring nerves. Since these nerves were disconnected from the CNS, the cross-talk is located peripherally. Here we tested if low-threshold mechanoceptive (LTM) C-fibers can be excited by this cross-talk and if this process is mediated by substance P (SP) via neurokinin-1 (NK-1) receptors. In urethane anesthetized rats we found that 80% (56/71) of LTM C-fibers, recorded in the lateral cutaneous branch of the dorsal ramus (CBDR) of T10 spinal nerve, were excited by a 10s, 20 Hz tetanus of the T9 CBDR. Compared to the spontaneous pre-tetanic firing frequency of 1.62+/-0.40 impulses/30s, the frequency significantly increased to 3.74+/-0.99, 3.17+/-0.69 and 2.92+/-0.63 impulses/30s, at 30, 60 and 90 s after the tetanus, respectively, and declined to the baseline frequency thereafter. When injected into their receptive fields, SP mimicked the tetanically induced increase of firing rate, whereas the NK-1 receptor antagonist WIN 51708 blocked the excitation in most fibers. The excitation was significantly diminished in adult rats that were neonatally treated with capsaicin, a treatment that destroys most SP-expressing afferent fibers. Thus, we conclude that peptidergic primary afferents are functionally linked with adjacent LTM C-fibers in a non-synaptic, paracrine-like signaling pathway via SP and NK-1 receptors, and perhaps also other agents as well. We propose that this cross-talk has evolved as a mechanism regulating the mechanoceptive characteristics of LTM C-fibers, presumably contributing to pain sensation elicited by tactile stimuli ('allodynia').     

Inward rectifier and low-threshold calcium currents contribute to the spontaneous firing mechanism in neurons of the rat suprachiasmatic nucleus

Intracellular and voltage-clamp studies were carried out to clarify the mechanism for spontaneous firing activity in neurons of the suprachiasmatic nucleus (SCN) of rat hypothalamic brain slices in vitro. SCN neurons displayed spontaneously firing action potentials that were preceded by a depolarizing pre-potential and followed by a short spike after-hyperpolarization (AHP). Injection of inward current with a duration longer than 50 ms resulted in a depolarizing voltage sag on hyperpolarizing electrotonic potentials. The inward rectification was depressed by bath application of caesium (1 mM) but not by barium (500 M). SCN neurons also showed a rebound depolarization associated with spike discharge (anodal break) in response to relaxation of hyper polarizing current injection. The rebound depolarization was reduced by nominally zero calcium. Cadmium (500 M), cobalt (1 mM) or caesium (1 mM) but not nicardipine also depressed the rebound depolarization. Under voltage-clamp conditions, hyperpolarizing steps to membrane potentials negative to approximately –60 mV caused an inward rectifier current, probably H current (I _H), which showed no inactivation with time. Bath application of caesium (1–2 mM) suppressed I _H. Caesium (2 mM) depressed the slope of the depolarizing spike pre-potential, resulting in a prolongation of the interspike interval of tonic firing neurons. We conclude that both the inward rectifier current, I _H, and the low-threshold calcium current contribute to the spike prepotential of spontaneous action potentials in firing neurons of the rat SCN.     

The need for control,safety and trust in healthcare: A qualitative study among adolescents and young adults exposed to family violence

ObjectiveAdolescents and young adults (AYA) exposed to family violence are in need of professional healthcare. However, only one-third of them seek professional help.MethodsThis study investigates healthcare needs of twelve AYA exposed to family violence. Semi-structured face-to-face interviews using purposive sampling to reach diversity. Open thematic coding was used to identify the most important themes.ResultsParticipants experienced emotional problems, distrusted others and felt unsafe as an important consequence of their exposure to family violence. All participants expressed a need for help, but as help involved informing others, they considered it unsafe. Trust, safety and control regarding healthcare interventions emerged as vital needs. The anonymity of the Internet was considered as offering safeguards in seeking and receiving help.ConclusionTrust, safety and control regarding healthcare interventions emerged as vital needs for AYA exposed to family violence. The great importance of being in control of healthcare interventions has not been reported earlier. A personal bond can lower the need for control.Practice implicationsTo comply with the three basic needs, healthcare providers should grant AYA as much control as possible while still monitoring patient safety. The Internet can be an important resource for offering low-threshold professional and peer support.     

The association between nocturnal trapezius muscle activity and shoulder and neck pain

The study investigated the possible association between nocturnal trapezius muscle activity and shoulder and neck pain. Sixty female subjects participated in the study, 33 were classified as pain-afflicted on the basis of shoulder and neck pain reports for the previous 6 months. Electromyographic (EMG) activity was monitored bilaterally from the trapezius in all recordings. EMG recording of the deltoid, biceps, and hand flexors was included for 26 subjects (17 with pain) to provide a comparative basis for evaluation of the trapezius recordings. There was considerable variation in the amount of muscle activity between subjects; however, some subjects presented a continuous, low-level activity pattern throughout the presumed sleep period. Subjects classified as pain-afflicted had significantly higher activity level and longer duration of trapezius EMG activity than the pain-free subjects. The deltoid had significantly more activity than the trapezius, while the biceps and the hand flexors presented similar activity level and duration as the trapezius. Nocturnal trapezius activity was not associated with pain exacerbation the same night. We suggest nocturnal trapezius muscle activity is a pointer to physiological mechanisms that contribute to some forms of shoulder and neck pain, such as trapezius myalgia, but nocturnal muscle activity may not be casually implicated in the pain-induction process.     

Interest in low-threshold employment among people who inject illicit drugs: implications for street disorder

Background

Income generation opportunities available to people who use illicit drugs have been associated with street disorder. Among a cohort of injection drug users (IDU) we sought to examine street-based income generation practices and willingness to forgo these sources of income if other low-threshold work opportunities were made available.

Methods

Data were derived from a prospective community recruited cohort of IDU. We assessed the prevalence of engaging in disorderly street-based income generation activities, including sex work, drug dealing, panhandling, and recycling/salvaging/vending. Using multivariate logistic regressions based on Akaike information criterion and the best subset selection procedure, we identified factors associated with disorderly income generation activities, and assessed willingness to forgo these sources of income during the period of November 2008 to July 2009.

Results

Among our sample of 874 IDU, 418 (48%) reported engaging in a disorderly income generation activity in the previous six months. In multivariate analyses, engaging in disorderly income generation activities was independently associated with high intensity stimulant use, as well as binge drug use, having encounters with police, being a victim of violence, sharing used syringes, and injecting in public areas. Among those engaged in disorderly income generation, 198 (47%) reported a willingness to forgo these income sources if given opportunities for low-threshold employment, with sex workers being most willing to engage in alternative employment.

Conclusion

Engagement in disorderly street-based income generation activities was associated with high intensity stimulant drug use and various markers of risk. We found that a high proportion of illicit drug users were willing to cease engagement in these activities if they had options for causal low-threshold employment. These findings indicate that there is a high demand for low-threshold employment that may offer important opportunities to reduce drug-related street disorder and associated harms.     

Ca2+ signaling by T-type Ca2+ channels in neurons

Among the major families of voltage-gated Ca²⁺ channels, the low-voltage-activated channels formed by the Ca_v3 subunits, referred to as T-type Ca²⁺ channels, have recently gained increased interest in terms of the intracellular Ca²⁺ signals generated upon their activation. Here, we provide an overview of recent reports documenting that T-type Ca²⁺ channels act as an important Ca²⁺ source in a wide range of neuronal cell types. The work is focused on T-type Ca²⁺ channels in neurons, but refers to non-neuronal cells in cases where exemplary functions for Ca²⁺ entering through T-type Ca²⁺ channels have been described. Notably, Ca²⁺ influx through T-type Ca²⁺ channels is the predominant Ca²⁺ source in several neuronal cell types and carries out specific signaling roles. We also emphasize that Ca²⁺ signaling through T-type Ca²⁺ channels occurs often in select subcellular compartments, is mediated through strategically co-localized targets, and is exploited for unique physiological functions. Lucius Cueni and Marco Canepari contributed equally to this review.