Effect of Renal Impairment on the Pharmacokinetics and Tolerability of Tiagabine

Summary: Purpose: We wished to determine the effect of renal impairment on the pharmacokinetics and tolerability of the new antiepileptic drug tiagabine (TGB).
Methods: We assessed TGB pharmacokinetics and tolerability in 25 subjects with various degrees of renal function (based on creatinine clearance, n = 4–6 per group) from healthy (group I) to requiring hemodialysis (group V) in a single and multiple dose (every 12h), one-period (groups I-IV) or a single dose, two-period (group V) study (4-mg oral doses of TGB · HCl). Blood samples were collected after the first dose (both periods for group V) and after the last dose on day 5 (groups I-IV). TGB plasma concentrations and plasma protein binding were determined by high-performance liquid chromatography (HPLC) and ultrafiltration, respectively.
Results: TGB was well tolerated by all study subjects. The pharmacokinetics of TGB were similar in all subjects; no pharmacokinetic parameter (based on either total or unbound concentrations) was statistically correlated with creatinine clearance. For total TGB in plasma, single-dose mean values of the maximum plasma concentration, clearance, and half-life (t1/2) ranged from 52 to 108 ng/ml, from 7.14 to 11.02 I/h, and from 6.4 to 8.4 h, respectively.
Conclusions: TGB pharmacokinetics and tolerability were independent of renal function; therefore, dosage adjustment is unnecessary for epilepsy patients with renal impairment.     

ONE-STAGE ARTERIOVENOUS REVERSAL FOR REVASCULARIZATION OF SEVERELY ISCHEMIC LIMBS

Staged arteriovenous reversal has been successfully established forrevascularization of severely ischemic limbs since 1984. The authors tried to constrict thecentral venous limb immediately after the arteriovenous fistula formation to make the pres-sure distal to the anastomosis raising to its maximum to shorten the time required for thedistal valves to become incompetent. Thus, the revascularization of the severely ischemiclimbs may be established much sooner than the staged arteriovenous reversal, and more di-seased limbs will be saved. Forty-two patients with a total of 60 upper and lower limbshave been operated on with good results.     

"Chronic painter''s syndrome". A reanalysis of psychological test data in a group of diagnosed cases, based on comparisons with matched controls

Twenty solvent-exposed workers, most of them painters, had been diagnosed as cases of toxic encephalopathy in 1978/79. Two years later they were re-examined with an extensive battery of neuropsychological tests. Their performance was unchanged on retesting. We have now compared their test results with those of non-exposed control subjects. Previous impressions of significant intellectual impairment in the solvent-exposed patients could not be confirmed when the influence of age, education, and intelligence was taken into consideration. The present group with presumed toxic encephalopathy is assumed to be representative of other patients who were similarly diagnosed in our department. The presently reanalyzed cases had been diagnosed as brain damaged and reported as such in the literature. Thus, they may have contributed to the formation of the concept of the "chronic painters' syndrome" with dementia.     

Ischemic stroke in infancy,childhood, and adolescence

The authors studied 34 patients with juvenile ischemic cerebrovascular disease over a 15-year period. Of the 34 patients, 23 had intracranial occlusions attributed to cerebral thrombosis or embolism and 11 had occlusions resulting from moyamoya disease. Clinicopathological features were evaluated in the 23 cases with ischemic stroke, but not those with moyamoya disease. The cause of the arterial occlusion remained undetermined in 11 patients and was found to be an embolism based on congenital heart disease in 8, on trauma in 3, and on infection in 1. Cerebral angiography was performed in 21 patients. Of these, 17 had stenoses or occlusions corresponding to their symptoms. CT scans were performed in 10 patients; the lesion in question showed no stenosis or occlusion with cerebral angiography. With regard to prognosis, patients with unknown etiology had good outcomes compared with those with congenital heart disease. With respect to acute infantile hemiplegia, 10 patients had convulsive seizures and 4 had a history of an earlier infection. Angiography and CT scans in patients with congenital heart disease demonstrated arterial occlusive sites in the middle cerebral artery region. Three patients had abscesses after their ischemic lesions.     

肢体远隔缺血期适应联合后适应促进大鼠缺血性脑卒中模型神经发生的作用及机制

目的 探讨肢体远隔缺血期适应(per-conditioning,PerC)联合后适应(post-conditioning,PostC)对缺血性脑卒中后神经再生的作用,并明确PerC联合PostC对脂肪酸β-氧化(fatty acid β-oxidation,FAO)限速酶——肉毒碱棕榈酰转移酶(carnitine palmitoyl transferase 1A,CPT1A)的影响。方法 对成年雄性SD大鼠进行大脑中动脉闭塞(middle cerebral artery occlusion,MCAO)造模,MCAO模型后30 min进行肢体远隔缺血期适应治疗(PerC),再灌注24 h后重复进行肢体远隔缺血适应(PostC),1次/d,直到取材。再灌注14 d后对大鼠进行神经功能评分,通过免疫组织化学染色检测室管膜下区(subependymal ventricular zone, SVZ)神经再生情况,通过酶联免疫吸附测定(enzyme linked immunosorbent assay,ELISA)法检测CPT1A的表达。结果 与MCAO组及PerC/PostC组比较,PerC+PostC组大鼠,身体不对称运动行为评分降低,神经干细胞的数量以及向梗死区迁移的细胞数量增加。Pearson相关性分析显示,神经干细胞的数量与神经功能呈负相关(r=-0.917 9, P<0.0001)。然而,迁移到基底节区的神经干细胞的凋亡数量在各组之间差异无统计学意义。机制研究显示,PerC+PostC组CPT1A的蛋白水平显著增加。结论 PerC联合PostC治疗能够通过增加神经干细胞的数量改善神经功能,神经干细胞的脂肪酸氧化可能是其促进神经干细胞迁移的机制之一。     

基于多模态超声的颈动脉斑块致前循环卒中的风险分层研究

目的 探讨颈动脉斑块患者发生前循环缺血性卒中的临床及多模态超声(multimodal ultrasound, MMU)影响因素,构建基于超微血流成像技术(superb microvascular imaging, SMI)的风险分层预测模型。方法 回顾性分析颈动脉斑块患者683例,根据临床表现和多层螺旋电子计算机断层扫描(computed tomography, CT)/核磁共振扫描(magnetic resonance imaging, MRI),分为前循环卒中组(n=301)和非前循环卒中组(n=382)。收集患者颈动脉斑块的MMU特征、临床和实验室检查数据,采用多因素二元Logistic回归分析筛选出前循环缺血性卒中的影响因素。构建列线图风险预测模型,进行模型验证与风险分层。结果 前循环卒中组和非前循环卒中组年龄、体重指数(body mass index, BMI)、饮酒史、吸烟史、脑梗死既往史、高血压、糖尿病、低密度脂蛋白(low-density lipoprotein, LDL)、高密度脂蛋白(high-density lipoprotein, HDL)、同型半胱氨酸(hom...     

核苷酸结合寡聚化结构域样受体蛋白3炎症小体在脑卒中后认知障碍中的研究进展

脑卒中后认知障碍(PSCI)是脑卒中患者常见的并发症,严重影响患者的生活质量。目前,PSCI在临床治疗中尚未发现有效的针对性治疗措施。大量研究证实核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)炎症小体的活化在PSCI中起关键作用,且对其进行的许多抑制性治疗显示出了改善认知障碍的功效。为此,本文总结了NLRP3炎症小体的活化和影响因素及其与PSCI的关系,发现在PSCI的细胞和动物模型中,针对NLRP3或其炎症小体成分的抑制措施可以减轻炎性反应和相应的病理特征,从而促进其认知功能的恢复,因此,靶向NLRP3炎症小体可能是PSCI治疗的新趋势。然而到目前为止,尽管许多药物和治疗措施已成功鉴定出能够抑制NLRP3炎症小体的活化,但其在临床中的治疗效果和安全性仍有待进一步验证。     

老年人主观认知下降与慢性病共病的相关性分析

背景 主观认知下降（SCD）是阿尔茨海默病（AD）早期预防的目标阶段,AD与慢性病共病关系密切,但二者间相关性尚不十分明确。目的 探究老年人SCD与慢性病共病的相关性,为AD早期预防和干预提供理论依据。方法 于2021年1月至2022年6月,在广州市城市生活小区和养老机构以便利抽样法抽取≥60岁的老年人612例。采用基础版蒙特利尔认知评估量表（MoCA-B）、临床痴呆量表（CDR）、Hachinski缺血指数量表（HIS）评定客观认知功能水平,通过SCD标准诊断框架和SCD问卷（SCD-Q9）进行分组,将整体客观认知水平无异常、符合SCD标准诊断框架和SCD-Q9≥5分的老年人分入SCD组,将整体客观认知功能无异常和SCD-Q9<5分的老年人为认知无异常（CN）组。采用一般资料问卷收集老年人的社会人口学（性别、年龄、居住地、受教育年限、婚姻状况、退休前职业类型、月收入）和健康相关资料[体质指数、腰围、吸烟习惯、饮酒习惯、饮茶习惯、锻炼频率、午觉习惯及平均时长、睡眠质量、抑郁及焦虑症状、日常生活活动能力（ADL）],其中睡眠质量、抑郁症状、焦虑症状及ADL分别采用匹兹堡睡眠指数量表...     

中性粒细胞与淋巴细胞比值预测高龄卒中预后的价值

探讨中性粒细胞与淋巴细胞比值（NLR）对≥80岁急性缺血性脑卒中患者90 d预后的价值。方法 纳入2019年1月—2021年6月发病7 d内、≥80岁的缺血性卒中患者476例的相关信息、影像结果、随访结果,按照入组患者NLR的四分位数间距分为Q1组（NLR ＜2.97）、Q2组（ 2.97≤NLR ＜4.49）、Q3组（ 4.49≤NLR ＜7.94）、Q4组 （NLR≥7.94）,每组119例。根据不良结局发生率绘制K-M曲线,比较各组在不同时期的生存概率。采用Cox多因素回归分析影响患者不良预后的因素。结果log-rank检验显示,四组患者的生存率存在差异,Q4组的90 d生存率显著低于Q1组(P＜0.05)。多因素Cox回归分析显示,校正危险因素后,高NLR和高NIHSS评分是90 d死亡率的独立危险因素(P＜0.05)。根据ROC曲线,高NLR预测患者90 d死亡曲线下面积为0.74。结论 高NLR为影响≥80岁高龄急性缺血性卒中患者90 d预后的独立危险因素,对高龄急性缺血性脑卒中患者的90 d预后有预测价值     

低频脉冲电刺激联合摄食-吞咽训练在AIS后吞咽障碍的应用及疗效

探讨低频脉冲电刺激联合摄食-吞咽训练在急性缺血性脑卒中（AIS）后吞咽障碍的应用及对呼吸能力、吞咽功能、营养指标的影响。方法 选取本院2019年6月—2021年8月107例AIS后吞咽功能障碍患者,随机分为观察组（n=54）和对照组（n=53）,对照组给予摄食-吞咽训练,观察组在对照组的基础上使用低频脉冲电刺激治疗,两组均持续治疗1个月,比较两组治疗前后吞咽功能、舌骨喉复合体动度、喉镜吞咽功能(FEES)评估结果、呼吸功能、营养指标以及并发症发生情况。结果 观察组治疗后洼田饮水试验评定、标准吞咽功能评价量表（SSA）评分、吞咽功能初筛量表（EAT-10）评分低于对照组（P＜0.05）;观察组治疗后舌骨喉复合体动度包括舌骨向前、上移以及喉向前、喉上移最大幅度均大于对照组（P＜0.05）;观察组治疗后FEES评价中声带麻痹、食物渗漏、食物潴留、误吸比例低于对照组（P＜0.05）;观察组治疗后肺功能指标最长呼气时间、第一秒用力呼气容积（FEV1）、用力肺活量（FVC）以及最大吸气压（PImax）均大于对照组（P＜0.05）;观察组治疗后营养指标BMI指数、血清总蛋白（TP）、白蛋白（ALB）、转铁蛋白（TRF）、前白蛋白（PALB）水平均高于对照组（P＜0.05）;观察组吸入性肺炎发生率低于对照组,营养不良发生率为低于对照组（均P＜0.05）。结论 低频脉冲电刺激联合摄食-吞咽训练治疗AIS后吞咽障碍,可有效促进吞咽功能恢复,改善舌骨喉复合体动度,增强呼吸功能,提高营养状态,降低并发症发生风险