人体急性缺氧型循环代偿功能障碍

青年健康受试者89名,取安静坐位。在低压舱3、4、5、6、7千米模拟高度上停留30～120分钟,运用代偿率Z值和障碍度S对循环各指标进行综合性定量评定。循环障碍仅发生于5,000与6,000米,发生率分别为28.9％与55.0％。主要表现特征是心率锐减,血压急降,代偿率低达障碍水平Z≤-20以下,大多数障碍者伴有心律紊乱,严重时伴有苍白、恶心、冷汗与无力等。均属生理性障碍。吸入氧气后迅速消除。产生机理设想为高层次脑中枢首先调节失常,进而导致植物神经功能紊乱,由正常的交感神经占优势转为迷走神经张力过度增强,致使循环代偿功能随之障碍。     

自体同源膀胱的探索之路——由实验室走向商业化生产

由于肠组织和膀胱一样，都像气球，在其中充满液体时能够膨胀，而中空的时候会收缩，因此对于膀胱功能障碍患者来说，过去100多年以来的治疗方法，都是由外科医生切取病人的部分肠组织，将其改造成膀胱的尺寸和形状，以此发挥膀胱的作用，即所谓的膀胱成形术。     

模糊集理论在急性缺氧反应综合评定中的应用

对人体缺氧程度进行综合性定量评定是个有待解决的重要问题,本文试图应用模糊集理论对此加以探讨。在机体缺氧代偿理论的基础上,引入缺氧代偿率(Z)的概念,其中着重考虑了各循环指标在缺氧时所起作用的大小,并根据指标变化与症状分类符合的程度确定其值。按照模糊集理论再把被试者的不同代偿能力看作不同的模糊集合,并以 Z 为论域,分別构造出代偿好、代偿差和代偿一般三个模糊子集的隶属函数。依照模糊集中的隶属原则,可确定出给定 Z 值所代表的子集合,从而对不同被试者的代偿能力以及同一被试者不同缺氧时刻的代偿能力作出评价。在本文中代偿能力被分为五个等级:代偿最佳、代偿好、代偿一般、代偿差和代偿障碍。按此等级对39名被试者的缺氧代偿能力作出评价,取得了与实际非常一致的结果。     

中暑致肝损伤机制的研究进展

中暑是常发生在夏季高温环境或大量运动时的急危重症,可导致包括肝脏在内的多器官功能损害。中暑的发生及发展过程经历了代偿期、急性反应期和失代偿期。近年来国内外关于中暑致肝损伤机制方面的研究表明,中暑致肝脏功能损伤可能与热的直接作用、肝细胞内线粒体功能障碍和级联放大的炎症反应有关,各环节相互促进,最终导致肝脏的损伤。而且,在肝窦内的级联放大炎症反应在中暑致肝损伤中可能起主要作用。因此,本文对近年来中暑的病理生理和中暑致肝损伤机制方面的研究及进展作一综述,为中暑致肝损伤的临床防治提供思路。     

2型糖尿病进程中胰岛β细胞功能变化的分子机制

近年来,2型糖尿病(type 2 diabetes,T2D)发病率迅速上升,已成为全球性的健康危机。最近的临床和基础研究表明,胰岛β细胞功能障碍是导致T2D及其相关并发症的重要原因。在2型糖尿病的自然病程中,胰岛β细胞经历从代偿到失代偿的动态变化;其中,代谢应激反应,如内质网应激(endoplasmic reticulum stress,ERstress)、氧化应激(oxidativestress)和炎症(inflammation)是β细胞功能变化的关键调控机制。本文总结了β细胞功能在2型糖尿病病程中动态变化的研究进展,以期深化对2型糖尿病分子机制的理解,为精准诊断和临床干预2型糖尿病提供参考。     

急性低氧时狗心泵代偿-失代偿转变的力学特征

为了分析急性低氧时心泵代偿-失代偿转变过程的力学特征,在22条麻醉开胸狗上,于吸入气氧分压递降条件下,作了心泵舒缩功能测定。结果表明,虽然严重低氧时心泵外功功率尚可保持在增大状态,但其压力作功成分减小,容积作功成分增大。动脉导纳的增加是容积作功增大的主要原因。这时,主动脉内有效血液推动力进一步增大,而泵缩力量却开始减弱。肌力效应在泵失代偿发生前,对舒缩功能的增强起着重要作用。在泵代偿-失代偿转变阶段,斯塔林效应的作用显著。“舒-缩谐调”的变化,早在泵失代偿前就已出现,并渐明显,值得注意。     

人体急性缺氧性意识障碍

实验分为低压组(低压舱7,000米)与常压组(吸入7.6％低氧混合气),每组受试者各为12名,有7名参加了两组实验。每组各有4名平均经15分23秒发生了意识模糊或丧失(通称意识障碍)。障碍者的肺泡氧分压为29.9±0.8mmHg。障碍发生前,呈现严重无力,觉醒度降低,反应迟钝,脑波特征是高幅6波(100-300μV)占优势。障碍发生时,高幅δ波丧失节律,幅度衰减,波型不规则,额枕失同步;呼吸循环代偿功能增强程度明显高于障碍前。本工作对于预测和评价人体急性缺氧引起的意识障碍有意义。     

膀胱中辣椒素受体的分布和功能研究进展

膀胱中的辣椒素受体(TRPV1,VR1)主要来源于支配膀胱的感觉神经纤维和膀胱上皮细胞。表达TRPV1的初级感觉神经纤维主要分布在膀胱上皮的基层及基层下,而表达TRPV1的膀胱上皮主要是表层和基层细胞。膀胱中TRPV1的主要功能是感受伤害性刺激而致痛以及感受压力刺激而参与排尿反射。实验性膀胱炎和逼尿肌过度活动时,膀胱中的TRPV1表达增加或被磷酸化而增强其功能。通过脱敏或阻断剂以抑制TRPV1的功能,可以改善某些膀胱病变的症状。     

帕金森病的尿动力学表现及临床意义

为了评估有持久膀胱排尿障碍的帕金森氏病患者的尿动力学表现及其临床意义,对25例帕金森氏病患者行尿动力检查,并要求记录并回收24小时排尿日记.结果显示,1)有18例患者出现膀胱过度活动,逼尿肌收缩力低下或无反射4例,膀胱出口梗阻6例,另3例检查结果正常,无一例出现逼尿肌-括约肌协同失调; 2)患者所返回的排尿日记显示帕金森氏病患者普遍出现日排尿次数增加及每次排尿量的减少.由此可以得出结论:逼尿肌反射亢进是帕金森氏病患者尿动力学检查的最常见类型;尿动力学检查对正确处理帕金森氏病患者的排尿障碍有指导意义.     

尿源干细胞对神经源性膀胱大鼠膀胱功能及Notch1、Jagged1蛋白表达的影响

目的:研究尿源干细胞对神经源性膀胱大鼠膀胱功能及Notch1、Jagged1蛋白表达的影响。方法:纳入60只健康雌性清洁SD大鼠作为实验对象,将其按照随机抽签法分为正常对照组、研究组以及损伤组,每组各20只。其中研究组和损伤组大鼠均建立神经源性膀胱模型,研究组在造模成功后予以尿源性干细胞尾静脉注射。28 d后,比较三组大鼠膀胱功能相关指标水平,膀胱湿质量和膀胱湿质量/体质量,Notch1、Jagged1蛋白表达水平。结果:损伤组收缩时间、排尿量、膀胱峰压均低于正常对照组,而研究组收缩时间、排尿量、膀胱峰压均高于损伤组(均P0.05);损伤组膀胱基压高于正常对照组,而研究组膀胱基压低于损伤组(均P0.05)。损伤组膀胱湿质量和膀胱湿质量/体质量均高于正常对照组,而研究组膀胱湿质量和膀胱湿质量/体质量低于损伤组(均P0.05)。损伤组Notch1、Jagged1蛋白表达水平均高于正常对照组,而研究组Notch1、Jagged1蛋白表达水平低于损伤组(均P0.05)。结论:尿源干细胞的应用可显著改善神经源性膀胱大鼠膀胱功能,同时可下调Notch1、Jagged1蛋白表达水平。     

Deafferentation of the urinary bladder and implantation of a sacral anterior root stimulator (SARS) for treatment of the neurogenic bladder in paraplegic patients.

Since 25 years electrical stimulation has become an established and widely acknowledged therapy option. Today, FES is widely employed, e.g. for cardiostimulation, diaphragm stimulation, kinetotherapy, for treatment of tremor in Parkinson patients, and finally for bladder stimulation in patients with bladder voiding dysfunctions. Brindley was the first researcher who succeeded in stimulating the spinal nerves via implanted electrodes in an animal model. In the years 1978/79 Brindley implanted five paraplegic patients with so-called sacral anterior root stimulators; all of them were able to void under stimulation. This method of sacral anterior root stimulation (SARS) proved an alternative to frequent one-way catheterisation for patients with severe voiding dysfunctions, without achieving complete continence, however. The following study is to provide an overview over the latest insights in the context of implanting sacral anterior root stimulators; it discusses the preconditions required for such interventions and presents criteria to decide in which cases there is a contraindication for sacral deafferentation of the posterior roots. Moreover, it contrasts advantages and disadvantages of the intradural and extradural implantation methods and presents the currently available long-term follow-up results with SDAF and SARS for treatment of bladder voiding dysfunctions.     

Implantable Electrical Vesical Stimulator: Review of the Literature and Report of a Successful Case

Considerable interest has been shown recently in electrical stimulation of the incompetent urinary bladder. Two types of bladder stimulation have been attempted in dogs and in humans: (a) stimulation of nervi erigentes and (b) direct stimulation of the detrusor urinae muscle.After several years of animal experimentation, a vesical stimulator, built on a new electronic principle, was implanted successfully in a paraplegic patient who has a complete post-traumatic lower motor neuron lesion. The stimulator has been working satisfactorily since November 1965.This stimulator could eventually also be used in purely sensory sacral lesions, in well-selected incomplete lower motor neuron lesions, and in flaccid detrusors of the myogenic type.A review of the literature up to the time of this report shows only a few encouraging but incomplete results in humans. The techniques and the complexities involved in this problem are discussed.     

Stabilization of human standing posture using functional neuromuscular stimulation

Functional neuromuscular stimulation (FNS)/functional electrical stimulation (FES) is a potential way to restore some functionality to the limbs of patients with spinal cord injury through direct/indirect stimulation of the motoneuron. One of the constraints for wider use of FNS on paraplegic patients is the lack of efficient control algorithm. Most of the published works on FNS/FES control are based on oversimplified models of human body dynamics. An innovative control strategy for stabilizing the standing posture of paraplegic patients is proposed here which is a combination of a proportional-plus-derivative controller for motions of the skeletal system and a control action prediction mechanism to produce musculotendon activation. The goal is to produce musculotendon torque which can approximate those demanded by the controller for the skeletal system. In computer simulations, using a detailed skeletal–musculotendon–muscle activation dynamics model of human body, this FNS/FES control approach can stabilize a paraplegic patient's standing posture with the minimum number of musculotendon groups. Also, it is found that this control strategy can maintain stability even in the presence of reasonable variations in the controller's musculotendon parameters.     

Cell therapy with autologous mesenchymal stromal cells in post-traumatic syringomyelia

Background aims

Recently, clinical studies show that cell therapy with mesenchymal stromal cells (MSCs) improves the sequelae chronically established in paraplegic patients, being necessary to know which of them can obtain better benefit.

Patient controlled electrical stimulation via EMG signature discrimination for providing certain paraplegics with primitive walking functions

In this paper we present the first patient-based results for a micro computer-based EMG signature-controlled functional electrical stimulation (FES) system, for restoring walker-supported and brace-free primitive walking to complete paraplegics, at the patients own command. Stimulation is thus controlled directly by the patient's own EMG signatures, generated by him at will, and which are produced by him at his erector spinae back muscles (while activating these muscles more or less as he would during normal walking, had the person not been a paraplegic). In this manner a switch-free simplistic but reliable information-gap is produced across the paraplegic's lesion, such that the above lesion's relatively normal EMG provides the control command to electrical stimulation of paralyzed peripheral (lower limb) nerves, to provide the basic functions of standing up, sitting-down and walking. The FES signals are at pulse rates close to the average ones occurring naturally at the corresponding nerves. The paper reports actual patient results for 3 paraplegics, two at T-9 (one complete, one with only residual sensation) and one T-6 complete paraplegic, who all subsequently achieved walking between parallel bars and two even with a walker (no braces in all cases), using the FES system, this walking being, to our knowledge the first hand-switch-free patient-controlled FES walking reported ever. The EMG signature-discrimination for control is as previously developed by D. Graupe for artificial-limb control, and it depends only on the EMG signature temporal parameters, while completely ignoring EMG power (amplitude) level. Whereas all 3 patients produced EMG parameters in the range reported below, adequate for controlling all functions involved, only one, a T-6 complete paraplegic, has so far (due to time limitations) achieved EMG controlled walking between parallel bars and by now also a few steps with a walker. One T-9 complete paraplegic, injured 5 years before coming to our program, was however able, within 4 weeks, to walk via FES with a walker, though with manual control. Note that the present approach is valid only for upper motor neuron paralysis situations (intact peripheral nerves and muscles). We are thus also attempting to apply this approach to certain hemiplegics and quadraplegics, for restoring some upper limb functions, using EMG signals from the trapezius (shoulder) level.     

TENS attenuates response to colon distension in paraplegic and quadriplegic rats

Individuals with spinal cord injuries above thoracic level 6 experience episodic bouts of life-threatening hypertension as part of a condition termed autonomic dysreflexia (AD). The hypertension can be caused by stimulation of the skin, distension of the urinary bladder or colon, and/or muscle spasms. Transcutaneous electrical nerve stimulation (TENS) may reduce the severity of AD because TENS has been used to inhibit second-order neurons in the dorsal horn. Therefore, we tested the hypothesis that TENS attenuates the hemodynamic responses to colon distension. Eleven Wistar rats underwent spinal cord transection between thoracic vertebrae 4 and 5 (paraplegic, n = 6) or between cervical vertebra 7 and thoracic vertebra 1 (quadriplegic, n = 5). After recovery, all rats were instrumented with a radiotelemetry device for recording arterial pressure. Subsequently, the hemodynamic responses to graded colon distension were determined before and during TENS. During TENS the hemodynamic responses to colon distension were significantly attenuated. Thus TENS may be a preventive approach to reduce the severity of AD in paraplegic and quadriplegic individuals.     

Testicular function in patients with spinal cord damage.

Vaying degrees of testicular dysfunction are found in men with traumatic spinal cord damage. Eighteen paraplegic men have been studied and the gonadotropin response to luteinizing hormone-releasing hormone (LRH) measured. Basal serum testosterone estimations were made and in eight of the patients testicular testosterone reserve was assessed by the testosterone response to human chorionic gonadotropin (HCG). Testicular biopsies were performed in seven cases. In three of these patients, the testicular biopsies were abnormal. Five of the patients had elevated Follicle stimulating hormone levels and abnormalities of Luteinizing hormone kinetics were found in the same five patients. There was no significant difference between the plasma testosterone levels of the paraplegic patients when compared to the control group. In all the patients tested, there was an adequate testosterone reserve, and this included the three patients with the abnormal testicular biopsies. No relationship was found between the level of cord lesion and any of the hormonal parameters measured. This study confirms the primary nature of the seminiferous tubular damage which occurs in some patients with paraplegia.     

Cardiac homeostasis is independent of calf venous compliance in subjects with paraplegia

The purpose of this study was to examine cardiac hemodynamics during acute head-up tilt (HUT) and calf venous function during acute head-down tilt (HDT) in subjects with paraplegia compared with sedentary nondisabled controls. Nineteen paraplegic males (below T6) and nine age-, height-, and weight-matched control subjects participated. Heart rate, stroke volume, and cardiac output were assessed using the noninvasive acetylene uptake method. Venous vascular function of the calf was assessed using venous occlusion plethysmography. After supine measurements were collected, the table was moved to 10 degrees HDT followed by the three levels of HUT (10, 35, and 75 degrees ) in random order. Cardiac hemodynamics were similar between the groups at all positions. Calf circumference was significantly reduced in the paraplegic group compared with the control group (P < 0.001). Venous capacitance and compliance were significantly reduced in the paraplegic compared with control group at supine and HDT. Neither venous capacitance (P = 0.37) nor compliance (P = 0.19) increased from supine with 10 degrees HDT in the paraplegic group. A significant linear relationship was established between supine venous compliance and supine cardiac output in the control group (r = 0.80, P < 0.02) but not in the paraplegic group. The findings of reduced calf circumference and similar venous capacitance at supine rest and 10 degrees HDT in the paraplegic group imply that structural changes may have limited venous dispensability in individuals with chronic paraplegia. Furthermore, the lack of a relationship between supine venous compliance and supine cardiac output suggests that cardiac homeostasis does not rely on venous compliance in subjects with paraplegia.     

Relationships between muscle mitochondrial DNA content, mitochondrial enzyme activity and oxidative capacity in man: alterations with disease

Muscle mitochondrial content is tightly regulated, and requires the expression of both nuclear and mitochondrial genes. In addition, muscle mitochondrial content is a major determinant of aerobic exercise capacity in healthy subjects. The current study was designed to test the hypothesis that in healthy humans, muscle mitochondrial DNA (mtDNA) content is correlated with citrate synthase activity (a representative nuclear-encoded mitochondrial enzyme) and aerobic exercise capacity as defined by whole-body peak oxygen consumption (VO2). Furthermore, it was postulated that these relationships might be altered with disease. Twelve healthy and five paraplegic subjects underwent exercise testing and vastus lateralis muscle biopsy sampling. An additional ten healthy subjects and eight patients with unilateral peripheral arterial disease (PAD) underwent exercise testing and gastrocnemius muscle biopsy sampling. Citrate synthase activity and mtDNA content were positively correlated in the vastus lateralis muscles from the healthy subjects. This relationship was similar in muscle from paraplegic subjects. mtDNA content was positively correlated with peak VO2 in the healthy subjects and in the paraplegic subjects in whom peak VO2 had been elicited by functional electrical stimulation of the muscle. In contrast, the PAD subjects demonstrated higher mtDNA contents than would have been predicted based on their claudication-limited peak VO2. Thus, in healthy humans there are strong relationships between muscle mtDNA content and both muscle citrate synthase activity and peak VO2. These relationships are consistent with coordinant nuclear DNA and mtDNA expression, and with mitochondrial content being a determinant of aerobic exercise capacity. The relationships seen in healthy humans are quantitatively similar in paraplegic patients, but not in patients with PAD, a disease which is associated with a metabolic myopathy. The relationships between mtDNA content, mitochondrial enzyme activities and exercise capacity provide insight into the physiologic and pathophysiologic regulation of muscle mitochondrial expression.     

Model-based development of neuroprosthesis for paraplegic patients.

In paraplegic patients with upper motor neuron lesions the signal path from the central nervous system to the muscles is interrupted. Functional electrical stimulation applied to the lower motor neurons can replace the lacking signals. A so-called neuroprosthesis may be used to restore motor function in paraplegic patients on the basis of functional electrical stimulation. However, the control of multiple joints is difficult due to the complexity, nonlinearity, and time-variance of the system involved. Furthermore, effects such as muscle fatigue, spasticity, and limited force in the stimulated muscle further complicate the control task. Mathematical models of the human musculoskeletal system can support the development of neuroprosthesis. In this article a detailed overview of the existing work in the literature is given and two examples developed by the author are presented that give an insight into model-based development of neuroprosthesis for paraplegic patients. It is shown that modelling the musculoskeletal system can provide better understanding of muscular force production and movement coordination principles. Models can also be used to design and test stimulation patterns and feedback control strategies. Additionally, model components can be implemented in a controller to improve control performance. Eventually, the use of musculoskeletal models for neuroprosthesis design may help to avoid internal disturbances such as fatigue and optimize muscular force output. Furthermore, better controller quality can be obtained than in previous empirical approaches. In addition, the number of experimental tests to be performed with human subjects can be reduced. It is concluded that mathematical models play an increasing role in the development of reliable closed-loop controlled, lower extremity neuroprostheses.