【作者】 王剑火；

【导师】 侯春林； 陈爱民； 张伟；

【作者基本信息】 第二军医大学 ， 外科学， 2009， 博士

【摘要】 研究背景尿意缺失不仅给患者带来生活上的诸多不便,而且给患者家庭及社会带来巨大的负担。定时排尿是目前处理尿意缺失的主要方法,具有许多不足之处。排尿报警装置(Micturition Alent Devices, MADs)是一类能够对膀胱容量或压力进行实时监测并适时报警从而提醒患者排尿的设备,有望成为治疗尿意缺失的一种方法。从20世纪70年代开始,提出了多种设计方案,但均存在一定的不足之处。研究目的一、介绍根据指南针原理设计的排尿报警装置及模型。二、验证根据指南针原理设计的排尿报警装置的可行性。三、研究地磁场对根据指南针原理设计的排尿报警装置的影响以及防护措施。四、研究根据指南针原理设计的排尿报警装置的各种参数。五、研究根据指南针原理设计的排尿报警装置的体内植入部件的生物安全性。六、测量根据指南针原理设计的排尿报警装置的一项重要参数即成人的下腹壁厚度。研究方法一、通过对根据指南针原理设计的排尿报警装置的设计原理、基本结构及模型的介绍,从理论上论证该设计方案的合理性和可行性。二、应用自制的根据指南针原理设计的排尿报警装置模型通过体外模拟试验和动物试验验证该方案的可行性。三、通过体外模拟试验研究地磁场对根据指南针原理设计的排尿报警装置的影响,探讨相应的防护措施。四、通过体外模拟试验研究根据指南针原理设计的排尿报警装置的重要参数的作用规律。五、通过细胞毒性试验、致敏试验、皮内刺激试验、急性全身毒性试验、肌间及膀胱前壁植入试验评价根据指南针原理设计的排尿报警装置的体内植入部件即硅胶包埋的永磁铁的生物安全性。六、应用B超测量100例成人的下腹壁厚度和MRI测量37例成人耻骨联合上缘及其上方1、2、3、4和5cm的下腹壁厚度。研究结果一、根据指南针原理设计的排尿报警装置已获得国家发明专利(专利号:ZL 2006 1 0119438.7)。该装置是由体内的永磁铁和体外的报警仪两部分组成。永磁铁以硅胶薄膜包埋;报警仪实质上是一个由特殊开关控制的报警器,该开关具有指南针的功能,故被称为指南针开关,能够显示报警仪所在处的磁场方向。将永磁铁和报警仪分别固定在膀胱前壁和下腹壁,膀胱容量的变化导致永磁铁位置的变化,永磁铁位置的变化使报警仪所在处的磁场发生变化,磁场的变化使报警仪的指针发生旋转。当膀胱内尿量达到预设值时,报警仪自动报警,提醒患者排尿。与其它方案相比,该方案具有结构简单、节能等特点。报警仪模型是由指南针开关、蜂鸣器、电源和电源开关通过导线串联而成,指南针开关是由中心支轴、磁针和旁支轴组成,磁针垂直固定于中心支轴上并可绕中心支轴的轴线旋转,中心支轴和旁支轴均是导电性能良好的非铁磁性金属。由于普通的磁针磁性较弱,灵敏度较低,因此我们采用直径3mm的钕铁硼永磁铁条代替磁针,并增设一个指针,指针和磁条平行,均固定在中心支轴上,三者构成一体从而能绕中心支轴的轴线同时旋转,中心支轴穿过磁条的重心,指针也是导电性能良好的非铁磁性金属。二、体外模拟试验表明:报警仪读数与永磁铁位置呈正相关(r>0.622,P<0.05),模拟的腹壁厚度在2cm到4cm之间,两者间呈一一对应关系。模拟的腹壁厚度分别为2cm、3cm、4cm和5cm时,永磁铁均能使报警仪报警,开始报警时的永磁铁位置分别为6.1cm、6.3cm、6.7cm和7.4cm。动物试验表明:膀胱充盈量为25、50、75、100、125、150、175及200mL时报警仪的读数分别为74.6±0.9、79.6±1.2、84.5±0.9、90.1±0.8、95.5±1.1、101.8±2.1、110.5±2.9和121.9±3.5度。膀胱容量与报警仪读数具有一一对应关系,两者间成正相关(r=1.0, P<0.01)。当膀胱充盈量预设为150mL时,那么使报警仪开始报警的膀胱实际充盈量为147.6±8.0,误差小于15mL(10%)。犬的膀胱从初始状态被充盈到200mL,永磁铁平均上移距离为32.8±1.1mm。三、当报警仪的中心支轴与地磁场平行时,地磁场对根据指南针原理设计的排尿报警装置的监测结果没有影响;当中心支轴与地磁场垂直时,地磁场对该装置的监测结果影响最大;而当中心支轴与地磁场处于平行和垂直之间时,地磁场对该装置的监测结果有中等程度的影响。这种影响还与人体所处的方位、永磁铁的位置和腹壁厚度相关。四、报警仪读数与铁氧体永磁铁位置仅在腹壁厚度为2cm时具有相关性(r=0.632,P=0.021),而在3cm到9cm时不具有相关性(r<0.5,P>0.05)。报警仪读数与钕铁硼永磁铁的位置均具有相关性(r>0.622,P<0.05),且随永磁铁直径的增大而增强,随腹壁的增厚而减小。4种永磁铁的曲线之间的吻合度随腹壁的增厚而减小。五、硅胶包埋的永磁铁具有轻微的细胞毒性作用,无致敏作用、无皮内刺激作用和急性全身毒性作用。8只兔子肌间植入样品后,切口愈合良好,1只术后19天因纳差消瘦死亡,其它7只耐受性好;1年后样品周围组织炎症反应和纤维囊级别均为1级。实验组8条犬中,1条术后10小时死于手术并发症,另1条术后3周因肠道内铁丝被永磁铁吸住而出现肠梗阻,其它6条犬和对照组4条犬术后一般情况良好,精神、食欲及二便无明显异常,切口愈合良好,未发生感染,术后1年被处死。在这10条犬中,大网膜与膀胱壁在样品周围发生粘连,样品周围的纤维囊壁薄,其下方的膀胱壁增厚,膀胱粘膜面正常。样品周围组织炎症反应和纤维囊级别均为2级。术前和术后尿常规无明显异常。六、B超测量的成人下腹壁厚度为2.34±0.66 cm,与体重指数、体重、测量点到脐部的距离正相关(P<0.05),与膀胱的上下径、左右径和膀胱容量负相关(P<0.05),而与性别、身高、年龄、膀胱的前后径无相关性(P>0.05)。在耻骨联合上缘及其上方1、2、3、4和5cm,MRI测量的成人下腹壁厚度分别为5.26±1.65、3.45±1.34、3.10±1.03、3.02±1.05、2.92±0.97和2.95±0.98 cm,与膀胱容量无相关(P>0.05)。研究结论一、根据指南针原理设计的排尿报警装置设计合理、结构简单、容易制作、节能。二、体外模拟试验及体内动物试验均表明根据指南针原理设计的排尿报警装置是可行的。三、地磁场对根据指南针原理设计的排尿报警装置监测结果的影响与体位有关,可以通过采用适当的措施来避免或减少地磁场的影响。四、下腹壁厚度、永磁铁的磁性和永磁铁的移动幅度是根据指南针原理设计的排尿报警装置的三个重要参数,它们相互作用、相互制约,合理配置参数可以优化该装置的性能。下腹壁厚度在2～6cm的患者,直径10mm、厚3mm的钕铁硼永磁铁能够满足要求;下腹壁厚于6cm的患者,需要更强的永磁铁;下腹壁薄于2cm的患者,更弱的永磁铁可能更合适。五、根据指南针原理设计的排尿报警装置的体内植入部件即永磁铁经硅胶包埋后具有良好的生物相容性,符合临床使用要求。六、B超测量的成人下腹壁厚度平均为2.34cm,95%可信区间为2. 21～2. 47cm。在耻骨联合上缘及其上方1、2、3、4和5cm,MRI测量的成人下腹壁厚度分别平均为5.26、3.45、3.10、3.02、2.92和2.95cm,95%可信区间分别为4.71～5.81、3.01～3.90、2.76～3.45、2.67～3.37、2.60～3.25和2.62～3.28 cm。更多还原

【Abstract】 BackgroundPatients with a loss of micturition desire have a lot of difficulty in daily life,which gives their families and society gigantic burden. They have to rely on scheduled urination, which has, of course, a lot of disadvantages. Micturition alent devices (MADs) that can continuously monitor urinary bladder volume or pressure and alert the patient to urinate at right time may hopefully become an alternative for the treatment of loss of micturition desire. Several design protocols have been reported in the literature from 1970s, but they have some serious defects and can not be used clinically.ObjectivesFirst To introduce design and manufacture of a new micturition alent device on the principle of a compass.Second To validate the feasibility of the micturition alert device on the principle of a compass.Third To study the effect of the geomagnetic field on a micturition alert device on the principle of a compass.Fourth To study the primary parameters of the micturition alert device on the principle of a compass for the product design and clinical application of the device.Fifth To investigate the biocompatibility of silicon membrane embedded permanent magnets which are internal part of the micturition alert device on the principle of a compass.Sixth To measure the lower abdominal wall thickness which is one of important parameters of the device in adults for the product design and clinical application of the device.MethodsFirst The rationality and feasibility of the new micturition alent device on the principle of a compass was demonstrated by introducing the principle, elementary structure of the device.Second The feasibility of the micturition alert device on the principle of a compass was validated using home-made model of the device in vitro simulated test and vivo animal test.Third The effect of the geomagnetic field on a micturition alert device on the principle of a compass was studied in vitro simulated test and the possible protection measures were discussed.Fourth The primary parameters of the micturition alert device on the principle of a compass and their interaction rules were studied in vitro simulated test.Fifth The biocompatibility of silicon membrane embedded permanent magnets which are internal part of the device was evaluated both in vitro and in vivo including cytotoxicity test, sensitization test, primary skin irritant test and acute general toxicity test. Both the reaction of animals and pathology of the local tissue were observed after permanent magnets were implanted.Sixth The thickness of the lower abdominal wall was measured using ultrasound in 100 adults. The thickness of the lower abdominal wall at superior border of the pubic symphysis and 1,2,3,4 and 5cm above the pubic symphysis were measured using MRI in 37 adults.ResultsFirst This new micturition alent device on the principle of a compass patented by the national intellectual property rights bureau consists of an external alarm system and an internal permanent magnet. The permanent magnet is embedded with a silicon membrane. The alarm system is in fact an alarm controlled by a special switch which functions similarly to a compass and is therefore named a compass-switch. The alarm system can show the direction of the magnetic field where the central support axis is located. The alarm system is fixed on the lower abdominal wall outside and the permanent magnet is fixed on the bladder anterior wall. Any change in bladder volume would cause the change of the magnet position, which in turn causes the change of the magnetic field where the alarm is located and drives the hand of the alarm system to rotate. When the bladder volume reaches the preset value, the alarm buzzes automatically, alerting the patient to urinate. The design is characterized with simple structure and low power consumption when compared with other designs. A simple model of the alarm system included the dial, the compass switch, the buzzer, the power switch and the power supply and the latter four elements connected in series by wires to form the circuit. The compass switch consisted of the central support axis, the magnetic hand and the para-support axis. The hand was perpendicularly fixed on the central support axis and turned around the longitudinal axis of the central support axis. The central support axis and the para-support axis were made of non-magnetic metal of good conductivity. The N45 Brand NdFeB permanent magnetic rod with 3 mm in diameter took place of the magnetic hand because the magnetism of a common magnetic hand was not strong enough to work sensitively. A usual hand was then added that was made of non-magnetic metal of good conductivity. The hand and the magnetic rod were parallel and both fixed on the central support axis. Thus the hand, the magnetic rod and the central support can simultaneously turn around the longitudinal axis of the central support axis. The central support axis passes transversely through the gravity of the magnetic rod.Second In vitro simulated test, the correlation between the value of the model and the position of the magnet was significant(r>0.622,P<0.05), and more over, the correlation was one to one when the thickness of abdominal wall was from 2 to 4cm.The model began buzzing at the position of the magnet of 6.1, 6.3, 6.7 and 7.4cm when the thickness of abdominal wall was 2, 3, 4 and 5cm respectively. In animal test, the value of the model was 74.6±0.9, 79.6±1.2, 84.5±0.9, 90.1±0.8, 95.5±1.1, 101.8±2.1, 110.5±2.9 and 121.9±3.5°at the filling volume of 25, 50, 75, 100, 125, 150, 175 and 200 ml. They were positively correlated with one to one (r =1, P<0.01). When the bladder filling was preset at 150 ml, the model began buzzing at a factual filling of 147.6±8.0 ml, with the deviation error being less than 15 ml (10%). The shifting distance of the magnet from the initial filling state to 200 ml was 32.8±1.1mm.Third The geomagnetic field had no effect on the findings tested by the micturition alert device if the central fulcrum of the device parallelled with the direction of the geomagnetic field. The maximal effect occurred if the central fulcrum was vertical to the direction of the geomagnetic field. A moderate effect occurred corresponding to the acute angle between the central fulcrum and the geomagnetic field. Moreover, the effect was correlated with the position of body, the placement of permanent magnet and the thickness of abdominal wall.Fourth The value of the alarm system was correlated with the position of ferrite permanent magnet only when the thickness of simulated abdominal wall was 2cm(r=0.632,P=0.021), otherwise not(r<0.5,P>0.05). The correlation between the value of the alarm system and the position of NdFeB permanent magnets was significant(r>0.622,P<0.05), and intensified with the increasing diameter of NdFeB permanent magnets, but weakened with the increasing thickness of simulated abdominal walls.Fifth No sensitization, no stimulation, no acute general toxicity was observed except slight cytotoxicity to silicon membrane embedded permanent magnets. Wound healing was normal after muscular implantation of permanent magnets in 8 rabbits, one of which died from emaciation and others lived with excellent tolerance. The grade was 1 of the inflammatory reaction and fibrous capsule of the local tissue around the grafts. Among 8 dogs of the experimental group, one died from operation complications 10 hours after operation, another dog had intestinal obstruction 3 weeks after operation because iron wires in the intestinal tract was attracted by the permanent magnet and the other 6 dogs and 4 dogs of the control group were killed 1 year after operation which showed excellent tolerance with no abnormality in spirit, appetite, urine or stool and without any infection. Adhensions occurred between the epiploon and the bladder wall around permanent magnets in these 10 dogs. The fibrous capsule around permanent magnets was thin, the local bladder wall below permanent magnets was thickened, but the bladder mucosa was normal. The grade was 2 of the inflammatory reaction and fibrous capsule of the local tissue around the grafts. The findings of urine before and after operation were normal.Sixth The thickness of the lower abdominal wall was 2.34±0.66cm. The lower abdominal wall thickness was positively correlated with the weight, BMI and the distance from the measuring point to umbilicus(P<0.05), and was negatively correlated with bladder volume, laterolateral and craniocaudal diameters of the bladder(P<0.05), Their was no correlation of the lower abdominal wall thickness with gender, age, height and anterior-posterioral diameters of the bladder(P>0.05). The thickness of the lower abdominal wall at superior border of the pubic symphysis and 1,2,3,4 and 5cm above the pubic symphysis was 5.26±1.65, 3.45±1.34, 3.10±1.03, 3.02±1.05, 2.92±0.97 and 2.95±0.98 cm. Their was no correlation of the lower abdominal wall thickness with bladder volume(P>0.05).ConclusionsFirst The new micturition alent device on the principle of a compass was demonstrated with reasonable design, simple structure and low power consumption.Second It was feasible for the micturition alert device on the principle of a compass.Third The effect of the geomagnetic field was correlated with body position on the findings tested by the device. Some measures may be taken to avoid or decrease the effect of the geomagnetic field on the device.Fourth The thickness of abdominal walls, the position and magnetism of permanent magnets are three important parameters of the device. They are correlated with and affect each other. Reasonable parameters may optimize the device. NdFeB permanent magnets of 3mm thickness and 10mm diameter may meet the need for the patients with an abdominal wall from 2cm to 6cm thickness; stronger permanent magnets for the patients with an abdominal wall more than 6cm thickness and weaker permanent magnets for the patients with an abdominal wall less than 2cm thickness.Fifth Silicon membrane embedded permanent magnets used in the device has excellent biocompatibility to meet the criteria for clinical application.Sixth The mean thickness of the lower abdominal wall measured using ultrasound was 2.34cm, and its 95% confidence interval was 22.1~24.7cm. The mean thickness of the lower abdominal wall measured using MRI at superior border of the pubic symphysis and 1, 2, 3, 4 and 5cm above the pubic symphysis was 5.26, 3.45, 3.10, 3.02, 2.92 and 2.95cm respectively, and its 95% confidence interval was 4.71~5.81, 3.01~3.90, 2.76~3.45, 2.67~3.37, 2.60~3.25 and 2.62~3.28cm.更多还原