Enhanced modulation of neuronal activity during antisaccades in the primate globus pallidus

The antisaccade task has been widely used to investigate theneural mechanisms underlying volitional movement control. Inthis task, subjects suppress reflexive saccades to the suddenappearance of peripheral visual stimuli (prosaccades) and generatea saccade in the opposite direction. Recent imaging studiessuggest that the globus pallidus (GP) is involved in the generationof antisaccades. To understand the roles of the GP, we examinedsingle neuron activity and the effects of local inactivation.Monkeys were trained to make either a pro- or antisaccade accordingto prior instruction provided by the color of the fixation pointin each trial. Among 119 saccade-related neurons, 55% showedincreased firing rates associated with saccades, whereas theremaining neurons showed decreased firing rates. For both populationsof neurons, the activity modulation was enhanced during thepreparation and execution of antisaccades, as compared withprosaccades. Inactivation of the recording sites in the externalsegment of the GP resulted in an increase in the number of errortrials in the antisaccade tasks, suggesting that signals inthe GP may play roles in suppressing inadequate prosaccadesin the task. Signals in the GP might regulate eye movementsthrough the nigro-collicular descending circuitry and throughthe basal ganglia–thalamocortical pathways.     

Neural activity of the globus pallidus interna and its anatomical relations to the optic tract in Parkinson's disease

Summary. Summary.   Background: To reveal landmarks for placing the globus pallidus interna (GPi) target on MR images, visual evoked potentials (VEPs) of the optic tract (OT) and neural activities of the GPi were studied retrospectively.   Methods: The dorsal and lateral border of the OT were determined by VEPs of the OT, and neural activity in the pallidal region was recorded with a semimicro-electrode in 20 patients. The Unified Parkinson's Disease Rating Scale (UPDRS) was used to assess the condition of each patient before and 6 months and 12 months after surgery.   Findings: The location of trajectories relative to the lateral border of the OT were 3 mm medial (−3) in 6, 2 mm medial (−2) in 7, 1 mm medial (−1) in 8, at the lateral border (0) in 6, 1 mm lateral (+1) in 5, 2 mm lateral (+2) in 6, and 3 mm lateral (+3) in 5. The mean amplitudes along trajectories −3 and −2 mm were significantly higher than the others (post-hoc, p<0.01). In dorsoventral relations, the amplitudes from 5.1 mm to 6.8 mm of the medial trajectories (−3 to 0 mm) were significantly higher than others (post-hoc, p<0.01). The lesions placed medial to the lateral border of the OT located just above the lateral border of the OT on postoperative MR images (n=12) and brought better surgical benefits of total motor score, rigidity and bradykinesia than those placed lateral to the OT (n=8).   Interpretation: Our data indicate that hyperactive cells of the GPi are located medial to the lateral border of the OT and at least 5.1 mm above its dorsal surface, and this corresponds to the area just above the lateral border of the OT on MR images. Published online August 12, 2002     

Pharmacological modulation of experimental phasic and tonic muscle pain by morphine,alfentanil and ketamine in healthy volunteers

BACKGROUND: Muscle pain is a major clinical problem but the underlying mechanisms and its pharmacological modulation need further investigation. This study on 15 volunteers evaluates if two experimental muscle pain models are sensitive to micro -receptor agonists and to an N-methyl-D-aspartate (NMDA)-receptor antagonist. METHODS: In the left tibialis anterior, intramuscular electrical (IMES) pain thresholds were determined for single (SPTmuscle) and five (RPTmuscle) repeated stimuli. Also pain to suprathreshold stimulation at 150% of RPTmuscle, 10 s, was assessed on a visual analog scale (VAS) as AUCimes (area under the VAS curve). In the right TA muscle, pain intensity on infusion of 0.5 ml of hypertonic saline, 5% (AUCsaline) and pain distribution indicated as local and referred were evaluated. Pain variables were assessed before, during and after intravenous infusions of morphine (10 microg x kg-1 min-1, 10 min), alfentanil (target-controlled infusion, plasma concentration; 60 ng ml-1, 60 min) and ketamine (10 microg x kg-1 min-1, 60 min). All data were normalized to baseline pain values (before drug infusions were initiated) and compared with placebo (midazolam, 2 microg x kg-1 min-1, 10 min). RESULTS: SPTmuscle increased (log mean values +/- SD, mA) with morphine (0.11 +/- 0.17, P < 0.05), alfentanil (0.28 +/- 0.24, P < 0.001) and ketamine (0.19 +/- 0.18, P < 0.01) as compared with placebo (-0.03 +/- 0.12). Alfentanil and ketamine also increased RPTmuscle (0.25 +/- 0.21, P < 0.01 and 0.21 +/- 0.19, P < 0.05, respectively) as compared with placebo (0.00 +/- 0.17). Pain to IMES (AUCimes) was reduced (median values [25th-75th percentiles], cm x s) by alfentanil and ketamine (-19.7 [-14.6 - -29.6] and-12.8 [-8.3 - -27.8], P < 0.05, respectively) vs. placebo (-0.8 [1.6 - -12.3]). Similar drug effects were seen when pain to infusion of hypertonic saline (AUCsaline) was assessed (alfentanil:-388 [-99 - -677] and ketamine:-326 [-227 - -573], P < 0.05 compared with placebo: 150 [449--240]). Ketamine also reduced the size of the local pain area (-58.4 [-21.2 - -176.1], < 0.05) as compared with placebo (-0.4 [70.6 - -13.4]). The frequency of referred pain was also lower when ketamine was given (3/13, P < 0.05) vs. placebo (9/14). CONCLUSION: The study demonstrates that experimental muscle pain induced in humans by electrical stimulation and infusion of hypertonic saline is sensitive to pharmacological modulation similar to preclinical animal tests and clinical trials. The data suggest that these models can be valuable tools in analgesic drug development.     

Changes of phasic and tonic smooth muscle function of jejunum in type 2 diabetic Goto-Kakizaki rats

AIM: To generate phasic and tonic stress-strain curves for evaluation of intestinal smooth muscle function in type 2 diabetic rats during active and passive conditions.METHODS: Seven diabetic Goto-Kakizaki (GK) male rats, 32-wk old (GK group), and 9 age-matched normal Wistar rats (Normal group) were included in the study. Jejunal segments were distended up to a pressure of 10 cm H₂O in an organ bath containing 37 °C Krebs solution with addition of carbachol (CA). The pressure and outer diameter changes were synchronously recorded. Passive conditions were obtained using calcium-free Krebs solution containing ethylene glycol tetraacetic acid and papaverine. Total phasic, tonic and passive circumferential stress and strain were computed from the diameter and pressure data with reference to the zero-stress state geometry. The active phasic and tonic stresses were defined as the total phasic and tonic stresses minus the passive stress.RESULTS: Diabetes increased jejunal mucosa and muscle layer thicknesses compared to the Normal group (mucosa, 755.8 ± 63.3 vs 633.1 ± 59.1 μm, P < 0.01; muscle, 106.3 ± 12.9 vs 85.2 ± 11.7 μm, P < 0.05). The pressure and stress thresholds were decreased in the GK group after CA application compared to distensions without CA application (pressure, 1.01 ± 0.07 vs 1.99 ± 0.19 cmH₂O, P < 0.01; stress, 0.11 ± 0.01 vs 0.24 ± 0.02 kPa, P < 0.01). CA application did not change the pressure and stress threshold in the Normal group (pressure, 2.13 ± 0.32 vs 2.34 ± 0.32 cm H₂O, P > 0.05; stress, 0.25 ± 0.03 vs 0.35 ± 0.06 kPa, P > 0.05). The amplitude of total phasic, total tonic, active phasic and active tonic circumferential stresses did not differ for the distensions without CA application between the GK group and the Normal group. However, the total phasic and total tonic stresses increased after CA application in the GK group compared those in the Normal group. When normalized to muscle layer thickness, the amplitude of active stresses before CA application was lowest in the GK group compared with the Normal group. No difference was found during CA application.CONCLUSION: The stress generated by intestinal muscle normalized to the muscle layer thickness was lowest in GK rats compared to normal rats whereas the response to CA stimulation was preserved.     

Short and long-term motor and cognitive outcome of staged bilateral pallidotomy: a retrospective analysis

Summary Background. We investigated retrospectively the short and long-term motor and cognitive functioning of staged bilateral pallidotomy using motor testing and a comprehensive neuropsychological battery before and after each procedure. Methods. Fifteen patients with idiopathic Parkinson’s disease were assessed at baseline and at least 3 months after each of their two staged surgeries. Motor and neuropsychological results were compared to 15 non-surgical Parkinson’s disease patients matched for disease stage and mental status. In addition, nine bilateral pallidotomy patients were evaluated for long-term cognitive changes (>2 years). Findings. Bilateral pallidotomy patients demonstrated significant improvements in motor functioning in the “on” and “off” states and with dyskinesias after the first surgery, with an additional improvement reported for dyskinesias after the second procedure. On long-term follow-up, dyskinesia improvements were maintained. Bilateral pallidotomy patients did not show significant cognitive declines following both procedures on the short-term follow-up and when compared to the Parkinson’s disease group. However, significant cognitive declines were found on the long-term follow-up evaluation. Conclusions. Parkinson’s disease patients received significant short- and long-term motor benefits, particularly reduced dyskinesias, following staged bilateral pallidotomy without significant short-term cognitive consequences. Two years following the second procedure, bilateral pallidotomy patients tended to show an increase in both motor and non-motor symptoms of Parkinson’s disease, particularly cognitive decline.     

合并帕金森病股骨转子间骨折的手术治疗

背景：目前国内外对合并帕金森病的股骨转子间骨折的手术治疗报道较少,缺乏相关的临床诊治经验。目的：探讨对合并帕金森病的股骨转子间骨折患者进行手术治疗的特点及围手术期处理。方法：回顾分析2004年2月至2013年2月我院收治的股骨转子间骨折合并帕金森病的14例患者的临床资料,其中Jen．sen．EvansIII型3例,Ⅳ型6例,V型5例。男4例,女10例;手术时年龄66～92岁,平均78．2岁。6例行滑动加压动力髋螺钉固定（含2例TSP接骨板）,8例行髓内固定系统固定。根据Harris评分系统对所有患者进行术前和术后随访功能评定。结果：5例患者在术后1年内因肺部感染和心力衰竭死亡;9例完成随访,随访时间3～60个月,平均28．7个月。Harris评分由术前20．2分（16～26分）改善至末次随访时76-3分（62～85分）。所有随访患者在术后3个月内骨折基本愈合,未出现切口感染、髋内翻畸形、拉力螺钉切出股骨头及术后再骨折等并发症。结论：对于合并帕金森病的股骨转子间骨折患者,如果手术方式和内固定种类选择适当,并注意围手术期并发症防治,可以取得较好的临床疗效。但由于帕金森病对术后恢复影响较大,此类患者预后差于单纯髋部骨折患者。     

Interstitial cells and phasic activity in the isolated mouse bladder

OBJECTIVE: To describe the distribution of interstitial cells (ICs, defined as cells which show an increase in cGMP in response to nitric oxide, NO) in the isolated mouse bladder, and changes in phasic contractile activity after exposure to a NO donor. MATERIALS AND METHODS: The whole bladder was removed from 17 female mice, killed by cervical dislocation. For immunohistochemistry (six mice) the bladder was incubated in carboxygenated Krebs' solution at 36 degrees C, containing 1 mm of the phosphodiesterase inhibitor isobutyl-methyl-xanthine. Individual pieces of tissue were exposed to 100 microm of the NO donor diethylamine NONOate for 10 min; control tissues remained in Krebs' solution. Tissues were then fixed in 4% paraformaldehyde and processed for cGMP immunohistochemistry. Bladder pressure was measured in bladders from 11 mice; the bladders were cannulated via the urethra and suspended in a heated chamber containing carboxygenated Tyrode solution at 33-35 degrees C and intravesical pressure recorded. All drugs were added to the solution bathing the abluminal surface. RESULTS: NO induced an increase in cGMP in cells in the outer layers of the bladder wall, forming two distinct types based on their location; cells lying on the surface of the muscle bundles (surface muscle ICs) and cells within the muscle bundles (intramuscular ICs). Cholinergic nerve fibres were identified by the expression of vesicular acetylcholine transporter and neuronal NO synthase (nNOS). Choline acetyltransferase- and nNOS-positive nerves also had high cGMP levels in response to 100 microm diethylamine NONOate. In vitro exposure of an isolated whole unstimulated bladder to 100 microm diethylamine NONOate had no effect on resting bladder pressure. When whole bladders were exposed to muscarinic stimulation (30-100 nm arecaidine) there was an initial large transient rise in pressure followed by complex phasic changes in pressure. Adding 100 microm diethylamine NONOate abolished this phasic activity. Interestingly, the phasic activity was inhibited midway between the peak and trough of a phasic cycle. Such a pattern of inhibition might reflect the complexity of the phasic activity involving both excitatory and inhibitory components. CONCLUSIONS: These data show the presence of NO/cGMP-sensitive ICs in the outer muscle layers of the mouse bladder. Activating these cells alters the pattern of muscarinic-induced phasic activity. We suggest that the role of the ICs in the outer muscle layers is to generate and modulate phasic activity. If so, then this is the first report of a functional role for ICs in the bladder.     

Repeatability of phasic muscle activity: performance of surface and intramuscular wire electrodes in gait analysis

Repeatability is an important consideration for gait analysis data that are being used as an adjunct to clinical decision making. An index of repeatability may be based on a statistical criterion (variance ratio) that reflects similarity of wave forms over a number of identical cycles. The purpose of this study was to use the variance ratio to assess the repeatability of phasic muscle activity recorded with surface and bipolar intramuscular wire electrodes during gait on 10 normal subjects. Variance ratios were calculated using rectified and smoothed electromyographic data recorded simultaneously from the two types of electrodes. Three measures of repeatability (reproducibility, reliability, and constancy--defined as the cycle-to-cycle, run-to-run, and day-to-day repeatability of phasic muscle activity) were used to compare the performance of the two electrode techniques. Results show that the reproducibility and reliability were better for surface electrodes than for intramuscular wire electrodes, and constancy was good for surface electrodes and poor for intramuscular wire electrodes. Repeatability improved with increasing smoothing window lengths but was better for surface electrodes than wire electrodes, irrespective of the smoothing window. This study indicates that surface electrode data represent a more consistent measure of activity of superficial muscles, if comparisons are to be made between gait data from different test days.     

七氟醚抑制帕金森病患者切皮时肾上腺素能反应的最低肺泡有效浓度

目的探讨七氟醚抑制帕金森病(PD)患者切皮时肾上腺素能反应的最低肺泡有效浓度(MAC_(BAR))。方法选择2019年10月至2021年3月择期行脑深部刺激器植入术患者21例,男10例,女11例,年龄40～64岁,BMI 18～30 kg/m~2,ASAⅠ—Ⅲ级。采用吸入8%七氟醚进行麻醉诱导,喉罩置入后调整呼气末七氟醚浓度(C_(ET)Sev)至预设水平。采用序贯法测定七氟醚MAC_(BAR)。第1例患者C_(ET)Sev调整至3%,稳定后15 min切开锁骨下皮肤。将切皮前3、1 min HR和MAP的平均值记录为基础值,将切皮后1、3 min HR和MAP的平均值记录为变化值,若HR或MAP升高幅度超过基础值的20%则定义为肾上腺素能反应阳性。若切皮时肾上腺素能反应为阳性,下一例采用高一级浓度,否则采用低一级浓度,浓度梯度为0.2%。当出现7个"阳性反应-阴性反应"的转折点时停止试验。采用概率回归法计算七氟醚MAC_(BAR)及其95%可信区间(CI)。结果肾上腺素能反应阳性的患者MAP变化值明显高于肾上腺素能反应阴性的患者(P0.05)。通过概率回归法算得PD患者切皮时七氟醚MAC_(BAR)为2.11%(95%CI 1.94%～2.27%)。结论七氟醚抑制帕金森病患者切皮时肾上腺素能反应的最低肺泡有效浓度为2.11%(95%CI 1.94%～2.27%)。     

帕金森病大鼠颈动脉体球细胞移植后TH、GFAP和TNF-α表达的动态变化

目的：探讨帕金森病（PD）大鼠颈动脉体球细胞移植后细胞存活状况和宿主的反应。方法：立体定位注射6－羟多巴胺（6－OHDA）制备偏侧PD大鼠模型，右侧纹状体内分别移植入自、导体颈动脉体和胚胎大鼠中脑组织块，移植后2、4、8和12周用免疫组织化学法同步检测酪氨酸羟化酶（TH）阳性细胞数、移植区周围胶质纤维酸性蛋白（GFAP）和肿瘤坏死因子－α（TNF－α）表达水平的改变。结果：移植后12周与胚胎中脑组织移植组比较，自、异体颈动脉体球细胞移植组存活TH^ 细胞显著增多（P＜0．05），但自、异体颈动脉体球细胞移植组间比较差异无显著性。各移植组移植后2周，移植区内GFAP和TNF－α阳性数显著增高，移植后12周时下降，但仍高于健侧，差异仍有极显著性（P＜0．01）。结论：颈动脉体球细胞块移植治疗可显著提高TH^ 细胞存活率，而移植区GFAP和TNF－α的表达对其有不利影响。