【作者】 张静；

【导师】 柯美云； 孙晓红； 戴晴；

【作者基本信息】 中国协和医科大学 ， 内科学， 2009， 博士

【摘要】 摘要一功能性消化不良亚型的症状谱、不良生活习惯、精神心理和生活质量调查背景功能性消化不良(FD)是临床上常见的疾病,对不同人群的研究结果显示,FD的患病率存在较大的差异。造成这种差异的主要的原因之一是FD的诊断标准不同。FD是一种异质性疾病,不同的病理生理学机制导致了功能性消化不良的各种临床症状。基于上述理论罗马Ⅲ分类标准将FD分成餐后不适综合征(PDS)和上腹痛综合征(EPS)两个亚型,期望FD亚型的划分能对FD流行病学、病理生理学、临床研究和治疗策略的发展有所帮助。新分类标准的制定使FD患者的人群特点发生了改变。目的通过问卷调查比较不同亚型的FD患者之间在消化不良症状、与其他功能性胃肠病的重叠情况及对疾病的认知情况、饮食习惯、精神心理状态、生活质量、睡眠质量等方面的是否存在差异。对象和方法2008年7月至2009年4月就诊于我院消化科门诊的147例FD患者纳入本项研究,所有患者均符合FD罗马Ⅲ标准并被分为PDS、EPS、PDS和EPS重叠组。采用问卷调查的形式对不同亚型FD患者的病情、精神心理、睡眠、生活质量等各方面进行分析比较。结果1.147例FD患者中三个亚型的比例分别为PDS占38.1%,EPS占19.7%,PDS与EPS重叠(PDS+EPS)占42.2%。2.PDS与EPS和PDS+EPS在性别比例(p<0.05)和BMI比较有显著的差异(p<0.05)。EPS在文化程度和职业方面与PDS(p<0.05)和PDS+EPS有显著差异(p<0.05)。3.不同亚型最困扰患者的3个症状不同(p<0.01)。4.PDS组与PDS+EPS组在应激事件诱发症状出现方面差异有显著性(p<0.05)。PDS组与EPS组在劳累作为症状加重因素方面有显著性差异(p<0.05)。5. PDS+EPS组与嗳气的症状重叠的患者明显多于EPS(p<0.05),其他各亚型的重叠症状方面均无显著差异(p>0.05)。6.三个亚型患者的卫生经济学方面均无显著差异(p>0.05)。7.经常外出就餐的PDS患者明显多于EPS患者(p<0.05)。8. PDS对疾病的认知程度明显低于PDS+EPS患者(p<0.05)。9. PDS+EPS患者的睡眠质量较PDS和EPS差(p<0.05)。10.三个亚型FD患者焦虑抑郁评分情况无显著差异(p>0.05)。11. PDS+EPS患者的生活质量更差(p<0.05)。结论FD患者中以PDS+EPS患者比例最多。不同亚型患者在一般人口统计学、最困扰患者的症状、疾病认知、诱发加重因素、与其他功能性胃肠病重叠的某些方面存在某些差异。PDS+EPS患者的睡眠质量最差、生活质量评分最低。摘要二灌注法液体营养餐负荷试验评价健康志愿者近端胃适应性功能背景液体营养餐负荷试验(LNLT)是近年来出现的一种用于反映胃部感觉和运动功能的检测方法。常规的LNLT是通过吸管饮入的,称之为饮入法液体营养餐负荷试验(D-NLT)。D-NLT的最大入量(MIV)受摄入因素、人口统计学变量的影响较大。我们将D-NLT进行了改良,即通过鼻胃插管将液体营养餐灌注到胃内,称之为灌注法液体营养餐负荷试验(P-NLT)。目的采用P-NLT与胃内压(IGP)的测量相结合评价健康志愿者(HS)的近端胃适应性和感觉敏感性,比较P-NLT与D-NLT两种方法的异同及P-NLT灌注量可能的影响因素。对象和方法41例HS(平均年龄41.4±11.1岁,男性16例,女性25例,男女比例1：1.6,平均BMI 24.0Kg/m2)分别进行D-NLT和P-NLT(通过鼻胃肠插管),在进行液体营养餐负荷试验的同时采用灌注式液体测压系统测量胃内压及二维超声(2DUS)测量近端胃和远端胃的容积。P-NLT过程中采用VAS视觉10cm评分(VAS 0-10分)评价饱感。结果1. P-NLT与D-NLT相比,阈值入量和最大入量有显著差异(p<0.01),但是阈值胃内压和最大胃内压差异无显著性(p>0.05)。2. P-NLT与D-NLT相比,最大饱感时的近端胃面积、近端胃容积均有非常显著的差异(p<0.01),但在初始饱感水平差异无显著性(p>0.05)。3. P-NLT和D-NLT最大饱感时的最大入量与二维超声测得的近端胃面积(r=0.600,p<0.01)、近端胃容积(r=0.771,p<0.01)均有显著的相关性,但是P-NLT方法r值均大于D-NLT,且更接近1。但是两种方法中初始饱感时的阈值入量与近端胃面积、近端胃容积之间均无显著相关性(p>0.05).4. P-NLT与D-NLT相比,近端胃和远端胃的半排时间及2小时排空率无显著差别(p>0.05)。5. P-NLT中不同性别、年龄和BMI亚组之间的最大入量与胃内压力水平无显著性差异(p>0.05)。结论P-NLT结合胃内压测定方法具有较好的可行性、安全性和耐受性。P-NLT中最大入量与胃内压力的影响因素少,具有较好的可靠性。P-NLT排除了摄入因素和部分精神心理因素的影响,其最大入量有可能更真实的反映受试者的胃适应性。P-NLT最大饱感时的最大入量与二维超声测量指标的相关性更强,较D-NLT的方法更优越。摘要三三维超声胃重建评价健康志愿者近端胃适应性功能背景二维超声技术作为一种临床检查技术已经被广泛应用于近端胃适应性的研究,在2DUS基础上逐渐发展而来的三维超声(3DUS)能够清楚的显示全胃图像并精确测量胃的容积,在体外试验中显示了良好的准确性和精密度,成为一种评价近端胃适应性的影像学新方法,并逐渐受到广泛的关注。目的采用三维超声胃重建评价HS中应用P-NLT评价近端胃适应性的可行性、可靠性。对象和方法HS 10例(曾经参与P-NLT,20-45岁之间,平均年龄37.7±6.1岁,男性6例,女性4例,男女比例1.5：1,平均BMI=23.5±3.5Kg／m2),所有受试者均进行P-NLT (50ml/min,0.75Kcal/ml)的检查,检查过程中每间隔5分钟进行一次3DUS扫描,直到第25分钟。过程中采用VAS视觉10cm评分(VAS 0-10分)法进行饱感评价,并分别记录不同饱感评分时的灌注量及所用时间。结果1.第一次和第二次P-NLT的灌注量无显著性差异(p>0.05),显示P-NLT试验结果的可重复性好。2.将3DUS测量的初始饱感和最大饱感时的胃容积和面积与相应2DUS测量的参数进行比较,结果显示两种方法最大饱感时的最大入量与最大近端胃容积和最大近端胃切面面积相关性曲线基本平行,说明最大饱感时2DUS测量值与3DUS测量值有可比性。3.将不同饱感VAS评分测得的灌注量和不同时间3DUS测得的近端胃容积进行比较,发现其灌注量随VAS评分的增高趋势与近端胃容积随时间增大的趋势非常相似。结论P-NLT试验结果的可重复性较好。3DUS三维胃重建测量的近端胃容积变化评价近端胃的适应性更为准确和可靠,较2DUS有优越性。最大饱感时2DUS测量的近端胃最大容积和近端胃最大切面与3DUS测量的参数有可比性,可以将近端胃最大切面面积作为评价近端胃适应性的一种间接测量指标。摘要四灌注法液体营养餐负荷试验评价功能性消化不良患者的近端胃适应性功能背景FD的病理生理学机制非常复杂,近端胃的适应性障碍和胃部感觉高敏在FD的发病中都起着重要的作用。FD是一种异质性疾病,不同的病理生理学机制导致了功能性消化不良的各种临床症状。目的通过P-NLT结合胃内压,评价FD患者与HS之间在近端胃容受性及胃部感觉敏感性方面的差别。分析不同亚型FD患者及不同症状FD患者的近端胃适应性及胃部感觉敏感性之间是否存在差异。对象和方法69例FD患者(平均年龄44.5±14.3岁,男性27例,女性42例,男女比例1：1.6,平均BMI=20.3±3.1Kg/m2),按照罗马Ⅲ分类标准将FD患者分为PDS,EPS和PDS+EPS三个亚型,再将FD患者按照罗马Ⅲ分类与主要症状相结合的方法进行亚组分类,共分成7个症状亚组,所有FD患者均进行P-NLT(通过鼻胃肠插管)检查,同时采用灌注式液体测压系统测量胃内压及二维超声测量近端胃和远端胃的容积。P-NLT过程中采用VAS视觉10cm评分(VAS 0-10分)法进行饱感评价。结果1.FD患者与HS相比较在阈值灌注量与胃内压水平有显著差异(p<0.05),但是最大饱感水平差异无显著性(p>0.05)。最大饱感时的近端胃容积有显著差异(p<0.01),但是近端胃面积无显著差异(p>0.05)。2.将FD三个亚型与HS比较结果显示：PDS+EPS的阈值灌注量显著高于HS组(p<0.01), EPS组阈值胃内压显著低于HS组(p<0.01)。EPS的最大近端胃容积显著小于HS组(p<0.05),FD三亚组远端胃餐后90min的排空率均显著低于HS组(p<0.01)。3.将FD不同症状组与HS比较,PDS一餐后饱胀组的阈值灌注量显著大于HS组(p<0.05)。PDS-早饱组的阈值灌注量和最大入量均显著低于HS组(p<0.01)。EPS一混合组的阈值灌注量和胃内压均显著高于HS组(p<0.05)。FD各亚症状组之间比较显示,PDS-早饱组阈值灌注量与最大入量显著低于其他各亚组(p<0.05)。PDS-餐后饱胀组的最大入量显著大于PDS-早饱组及EPS-上腹痛组(p<0.05)。EPS-混合组近端胃远端胃排空较HS和其他FD亚组低(p<0.05)。PDS-餐后饱胀组远端胃餐后90分钟排空率显著低于HS(p>0.05)。EPS-上腹痛组远端胃排空率明显高于EPS-混合组和PDS和EPS重叠(p<0.01)。4.P-NLT初始饱感时的阈值入量近端胃容积有较显著的相关性(p<0.05),最大饱感时的最大入量与近端胃面积、容积均有显著的相关性(p<0.01)。结论P-NLT结合胃内压测定方法对于评价FD患者的近端胃适应性和敏感性有较好的可行性、安全性和耐受性。P-NLT中的阈值灌注量和最大入量对于区分FD患者的症状亚组有较大的意义,也提示不同FD症状的病理生理学基础存在差异,建议将PDS分为餐后饱胀和早饱亚亚组,指导诊断和治疗。更多还原

【Abstract】 Abstract I:Clinical Survey of Symptom Spectrum, Quality of Life and Psychological Status in Patients with Functional dyspepsiaBackgroundsDyspeptic symptoms are extremely common in the general population.Several reports exist on the prevalence and impact of dyspepsia in the general population. However, the results of these studies are strongly influenced by criteria used to define dyspepsia. It is generally assumed that dyspepsia, and especially FD, is a heterogeneous condition in which different pathophysiological mechanisms underlie different symptom patterns. The Rome III subdivision of FD was proposed under the assumption that different underlying pathophysiological mechanisms would be present in each of the subgroups and, consequently, that different treatment modalities would be most suitable for each subgroup.AimsThe aim of this study were to investigate the differences between FD patients of different subtype at the aspects of demographics, dyspeptic symptomology, eating habit,psychological condition, SF-36 quality of life (QOL) and so on.Subjects and Methods146 FD patients (59M,88F, mean 45.3yrs) surveyed with Rome III Modular Questionnaire were divided into three groups,Postprandial distress syndrome(PDS) Epigastric pain syndrome(EPS) and PDS mixed with EPS. The data including demographics, dyspeptic symptomology, QOL and psychological status (Zung depression and anxiety scale) were recorded. All the indexes were compared between different subtype of FD patients.Results(1)The proportion of the patients were PDS 38.1%, EPS 19.7%, PDS mixed with EPS 42.2%. (2) Difference was found in gender proportion and BMI level when PDS compared with EPS (p<0.05)and PDS+EPS(p<0.05), and there are significant difference in career(p<0.05) and education level(p<0.05).(3) The most disturb symptoms were significant different in the three subtypes(p<0.01).(4)For induced and increased factor for symptom presence, PDS subtype patients were more easy induced dyspepsia symptom because of stress events(p<0.05). But tired condition can aggravate patients symptom in PDS (p<0.05) and PDS+EPS (p<0.05),but not in EPS.(5)Belching was more frequent overlapping with FD in PDS+EPS subtype(p<0.05), no difference were obtained in other FGIDs overlapping with FD along the subtypes(p>0.05).(6)No difference were found in medical economics and psychological status(p>0.05).(7) Patients in PDS has bad eating habit as usually eating outside(p<0.05), and in the same subtype,the cognition degree for FD were significant lower than PDS+EPS group(p<0.05).(8) PDS+EPS patients has the worst sleep quality(p<0.05) and QOL in the three subtypes(p<0.05).ConclusionsPatients of PDS+EPS was the highest proportion in clinical.There are some difference exist in demographics, dyspeptic symptomology, bad eating habit,most disturb symptoms, overlapping with other FGIDS and QOL.Patients in PDS+EPS group has the worst sleep quality and QOLAbstractⅡUsing Perfusion Nutrient Load Test in Assessment of Gastric Accommodation in Healthy SubjectsBackgroundsRecently, Liquid Nutrient Load Test (LNLT) has been proposed and developed one of the potential non-invasive well-tolerated approach to assess gastric accommodation and hypersensitivity. In traditional LNLT, the nutrition liquid was ingested into stomach with a straw,so called Drinking Nutrient Load Test(D-NLT). In D-NLT, the Maximal Intake Volume (MIV) can be affected by subject sensory and others like demographic factors.So we modified D-NLT through inserting a nasal-gastric tube, and the nutrition liquid can be perfused into proximal stomach, so called Perfusion Nurient Load test(P-NLT). The aim of this study was to investigate two different ways of NLT (nutrition load test), drinking (D-NLT) and perfusion (P-NLT), in evaluation of gastric accommodation and hypersensitivity combined with Intra-gastric pressure. And analysing possible factor in P-NLT.Subjects and methods41 HS (aged 41.4±11.1 yrs,16M:25F, BMI 24.0Kg/m2) enrolled in this study. Each one randomly received D-NLT and P-NLT (through nasal-gastric tube) with a constant rate of 50 ml/min (0.75 kcal/ml) in separate day within one week. Meanwhile, intragastric pressure was recorded and 2D ultrasonography (2DUS) was used to measure both the proximal and distal gastric area during NLT. Visual analogue scale (VAS,0-10) was used to evaluate satiety during NLT.Results(1)The amount of nutrition liquid in P-NLT were higher than those in D-NLT at minimal and maximal satiety(p<0.01). However, there was no difference of the intra-gastric pressure between P-NLT and D-NLT at minimal and maximal satiety, (p>0.05). (2) The proximal gastric area and proximal gastric volume at maximal satiety in P-NLT were significantly higher than D-NLT (<0.01),but no difference were obtained at minimal satiety(p>0.05). (3)The amount of nutrition liquid at maximal satiety was significantly correlated to proximal gastric area(r=0.600,p<0.01),and proximal gastric volume (r=0.771,p<0.01) at maximal satiety in both P-NLT and D-NLT, but the correlation was stronger in P-NLT. (4)There were no difference at gastric emptying rate and T1/2 in proximal and distal stomach in both methods(p>0.05).(5) The intra-gastirc pressure and maximal intake volume were no different in P-NLT at different lever of age, BMI and gender (p>0.05).ConclusionsOur study suggests that P-NLT might be more accurate to predict gastric accommodation in HS, for there were no influenced factors, such as swallowing air, taste and psychological disturb. P-NLT is a feasible, safe and tolerable method in assessment of proximal gastric accommodation and hypersensitivity, because of the stability in MIV and IGP and better correlation with 2DUS parameters than D-NLT. Abstract III. Assessment Gastric Accommodation by Means of 3D Ultrasound ImagingBackgrounds2D Ultrasonography, a clinical method that is widely available, has shown applicability and validity for the study of gastric accommodation.3D ultrasound imaging was developed based on the 2D method. For better visualization of the total stomach and improved calculation of gastric volumes,3D ultrasound imaging of the gastric compartments was developed. It is important that validation of an imaging method to study gastric accommodation also include evaluation of its accuracy and precision in volume estimation in vitro and in vivo.AimsTo evaluate gastric accommodation Using 3D ultrasound imaging by means of gastric volumes calculation and verify validation of P-NLT in evaluation of gastric accommodation in HS.Subjects and MethodsA total of 10 HS (6Male,4Female, mean 37.7yrs, BMI 23.5 Kg/m2.)participated in the study. All subjects performed P-NLT through a nasal-gastric tube with a constant rate of 50 ml/min (0.75 kcal/ml). Meanwhile 3DUS was used for imaging of gastric volumes every 5 minutes until 25minutes. During the perfusion, VAS analogue scale (VAS,0-10) was used to evaluate satiety.The nutrition volume in different satiety scale and time consume has been recorded.Results(1).No difference was obtained in MIV between the first and the second P-NLT study, which confirmed the repeatability of P-NLT method(p>0.05). (2) Althought significant difference was found in proximal gastric volume and gastric area in maximal satiety (p<0.05)and proximal gastric area in minimal satiety(p<0.05) between 3DUS and 2DUS. There are good correlation between the two methods. (3) A similar trend was found between nutrition volume in different satiety and gastric volume by means of 3DUS. ConclusionsP-NLT has good repeatability in assessment of gastric accommodation.3DUS was superior to 2DUS for its accuracy and precision in volume estimation. Proximal gastric area in maximal satiety can be used as a indirect index to evaluation gastric accommodation.Abstract IV Perfusion Nutrient Load Test in Assessment of Proximal Gastric Accommodation in Functional Dyspepsia Patients -- A Preliminary StudyBackgroundsFunctional dyspepsia (FD) is a highly prevalent disorder. Although recent studies have investigated various pathophysiological mechanisms, the pathogen esis of FD remains obscure.Impaired gastirc accommodation and hypersensitivity are two important inPathophysiological mechanisms in Functional Dyspepsia.It is generally assumed that dyspepsia, and especially FD, is a heterogeneous condition in which different pathophysiological mechanisms underlie different symptom pattern.AimsUsing P-NLT to evaluate proximal gastric accommodation and hypersensitivity in FD patients and HS, combined with intra-gastric pressure,and investigate different pathophysiological mechanism in different type of FD patients.Methods and subjects69 FD patients(aged 44.5±14.3 yrs,27 Males,42 females, BMI 20.3±3.1Kg/m2) According with Roma III criteria, all FD patients can be divided into three groups, PDS, EPS and PDS mixed with EPS. Then divided into seven subgroups based on main symptoms. All patients performed P-NLT (through a nasal-gastric tube) and evaluated intra-gastric pressure with water-perfusion manometric system.Meanwhile 2D Ultrasonography was used to measure, proximal and distal stomach volume. During P-NLT, Visual analogue scale(0-10)were used to evaluate satiety sensory.Results(1)Compared with HS, the amount of nutrition liquid and intra-gastric pressure at minimal satiety were significant difference in FD patients (p<0.05), but no difference obtained at maximal Satiety(p>0.05).The proximal gastric Volume at maximal Satiety were significant lower than HS(p<0.01), but no difference obtained in proximal gastric area(p>0.05).(2) Compared with HS, the amount of nutrition liquid at minimal satiety were higher in PDS+EPS group(p<0.01), the IGP were lower in EPS group(p<0.01). The proximal gastric volume at maximal satiety in EPS group was significant lower than HS(p<0.05). In FD patients, the gastric emptying rate of distal stomach at 90min after P-NLT are significant lower than HS(p<0.01). No difference obtained in other parameters(p>0.05). (3)When compared all these parameter in symptom based subgroups and HS, We can find that the amount of nutrition liquid at minimal satiety in PDS-PD was higher than HS(p<0.05), but the intake volume in PDS-ES at minimal and maximal satiety were both lower than HS(p<0.01). IGP and MIV in EPS-M at minimal satiety were both lower than HS(p<0.05). According to comparison within subgroup, the amount of nutrition liquid at minimal and maximal satiety in PDS-ES were both the lowest in all subgroups(p<0.05).The amount of nutrition liquid at maximal satiety in PDS-PD was higher than EPS-P(p<0.05), but no difference obtained within other subgroups. As concerned with proximal gastric volume, the value at at maximal satiety in EPS-P was lower than HS(p<0.05) and the value at minimal satiety in EPS-M was higher than HS(p<0.01). The gastric emptying rate in proximal and distal stomach were both lower in EPS-M than HS (p<0.05)and other subgroups, so as in EPS-P(p<0.05).(4)The proximal volume at minimal and maximal satiety and proximal area (p<0.05)at maximal satiety were all correlated with intake volume in P-NLT(p<0.01).ConclusionsP-NLT combined IGP was a feasible, tolerable method in evaluating of proximal gastric accomodation and hypersensitivity in FD patients. The amount of nutrition liquid at minimal and maximal satiety is significance in FD subgroup division. We suggested that PDS should be divided into PDS-ES and PDS-PD, which may be helpful for diagnosis and treatment of FD.更多还原