应激性溃疡时幽门区局部一氧化氮含量变化对胆汁返流的影响及机理探讨

目的探讨胆汁返流与幽门区局部神经递质一氧化氮的变化对应激性溃疡发病的影响及可能的机理。方法采用冷束缚应激方法复制应激性溃疡的动物模型，将60只成年SD大鼠分为两部分，第1部分：对照组10只，溃疡组30只，用于观测影响应激性溃疡发生的相关因素；第2部分：左旋硝基精氨酸甲酯（L—NAME）预处理组10只（L—NAME组），生理盐水预处理组10只（生理盐水组），用于观测幽门区局部一氧化氮含量变化对其他因素的影响。分别检测各组胃内胆汁酸浓度、胃黏膜溃疡指数（Guth评分）以及胃内pH值，用生化试剂盒检测幽门区一氧化氮的含量。结果溃疡组应激结束后1h幽门区一氧化氮含量达到峰值（P〈0．01），应激结束后2h胃内胆汁酸浓度和pH值均达到峰值（P〈0．01），应激结束后4h胃内溃疡指数达到峰值（P〈0．01）。L-NAME组的胃内胆汁酸浓度、溃疡指数及一氧化氮含量较生理盐水组显著降低（P〈0．01，P〈0．05），而胃内pH值的差异无统计学意义（P〉0．05）。幽门区一氧化氮含量与胆汁酸浓度呈正相关（r=0．715，F=12．55，P=0．017）。结论幽门区一氧化氮含量变化与胆汁的返流量之间存在正相关关系，而L—NAME的幽门区局部干预使幽门区一氧化氮含量减少，幽门松弛程度降低，胆汁返流量也随之减少，进而降低溃疡指数，起到保护胃黏膜的作用。     

Indirect radionuclide cystography: a sensitive technique for the detection of vesico-ureteral reflux

The detection or exclusion of vesico-ureteral reflux (VUR) has classically been by micturating cystourethrography (MCUG). Radionuclide cystography will detect VUR but fails to provide the same detailed anatomical informations as MCUG. This study allowed a comparison of indirect radionuclide cystography (IRC) and MCUG in 65 children. Renal reflux was detected by IRC in 32% of renal units, while VUR was seen in 36% by MCUG. When a comparison was made with MCUG, IRC had a sensitivity of 74.1% and a specificity of 90.5%. The markedly reduced radiation dose, avoidance of a bladder catheter plus the ability to monitor the urinary tract constantly during the entire procedure should ensure that IRC is the examination of choice in follow-up studies for VUR in all toilet-trained children.     

Variation in the diagnosis of vesicoureteric reflux using micturating cystourethrography

  Variability in the interpretation of micturating cystourethrography by paediatric radiologists for the diagnosis of vesicoureteric reflux in children was evaluated. All 265 micturating cystourethrograms (MCUs) that were available from 304 consecutive children aged 0.5 – 61 months  –  who were investigated after their first urine infection between 1993 and 1995 as part of a prospective cohort study  –  were selected for interpretation. Three experienced paediatric radiologists from the same department independently interpreted the MCUs according to the grading system of the International Reflux Study in Children, from grades 0 to V, with the presence of intrarenal reflux also noted. Apart from being informed that urine infection was the indication for the MCU, no other clinical information was given to the radiologists. The indices of variability used were the percentage of agreement and the kappa statistic, expressed as a percentage. Both measures were weighted with integers representing the number of categories from perfect agreement. Disagreement was analysed for children and kidneys. For the diagnosis of vesicoureteric reflux in individual patients, including grade, the percentage of agreement was 96% – 97% (kappa 90% – 91%) and the weighted percentage of agreement was 96% – 98% (weighted kappa 93% – 94%). The same high level of agreement was present for individual kidneys, with a percentage of agreement of 97% – 98% (kappa 89% – 92%) and a weighted percentage of agreement of 98% – 99% (kappa 94% – 95%). There was near perfect agreement in the interpretation of radiological micturating cystourethrography among three experienced paediatric radiologists for the diagnosis and grade of vesicoureteric reflux. Any variations in the medical care of children suspected of having vesicoureteric reflux are not explained by differences in the reporting of this diagnostic test. Received June 19, 1996; received in revised form November 1, 1996; accepted December 6, 1996     

胆汁反流性胃炎的胃运动功能研究

目的:探讨胃排空改变以及胃窦平滑肌电节律紊乱在胆汁反流性胃炎发病中的可能机制。方法:对59例有慢性上消化道症状的慢性胃炎病人,根据胃镜下可见显著胆汁反流,胃液呈深黄色或深绿色,胃液pH≥3.0,甘胆酸浓度>58μg/ml,胃粘膜病理积分>9,判断为病理性胆汁反流(部分病人经:显象进一步证实)。胃镜下未见胆汁反流,胃液清亮,其余指标均未达上述标准者判断为非胆汁反流性。选出18例胆汁反流性胃炎病人(BRG组)和17例非胆汁反流性胃炎病人(NRG组),上述检查正常的10名健康志愿者(HC组)作为对照受检者进食一份双核素标记的标准餐,用照相机以1帧/2分钟连续动态照相120分钟,部分受试者又在空腹时检测胃窦肌电。结果:BRG组有明显的固、液体双相排空延迟,以固相延滞期(SLP)延长较为突出,而固体半排空时间(HSET)延长在很大程度上受到SLP延长的影响:NRG组仅有HSET显著延长。进一步胃电检测结果表明,各组间平均慢渡频率(MSWF)无显著性差异,出现胃电节律失常(DRM)在各组的分布为HC组1/7、NRG组3/10和BRG组7/13,严重程度BRG>NRG>HC。结论:胆汁反流性胃炎者有较严重的胃窦功能不良,且胃肌电可予进一步证实,胃底和十二指肠动力异常也可能与胆汁反流性胃炎的发病有关。     

胆汁返流性胃炎胃粘膜超微结构研究

为探讨胆汁返流性胃炎的发病机理和应用中药治疗此病的效果，作者进行了胃粘膜超微结构观察。在治疗前、后取胃粘膜做光、电镜检查，发现本病胃粘膜变化突出的特点是淋巴细胞侵入腺细胞内，溶解腺细胞，破坏细胞间联接装置，使腺腔破溃，腺管萎缩。以上变化可占全部病例的８７．５％。另一特点是腺细胞内出现微囊（８例中有４例），这在慢性胃炎尚未见有电镜观察报道。作者认为胆汁返流性胃炎可以是慢性萎缩性胃炎的前驱，而腺体萎缩的原因是由于淋巴细胞的浸润破坏；这为由细胞介导引起的胃腺细胞损伤提供了形态学依据。     

Ambulatory 24-hour esophageal pH monitoring

If 24-hour esophageal pH monitoring is to be a useful diagnostic tool, it must reliably discriminate gastroesophageal reflux patients despite daily variations in distal esophageal acid exposure. To address this issue, we studied 53 subjects (14 healthy normals, 14 esophagitis patients, and 25 patients with atypical symptoms) with two ambulatory pH tests performed within 10 days of each other. Intrasubject reproducibility of 12 pH parameters to discriminate the presence of abnormal acid reflux was determined. As a group, the parameters of percent time with pH<4 (total, upright, recumbent) were most reproducible (80%). Therefore, a subject was defined as having gastroesophageal reflux disease if at least one of these three values were abnormal. Intrasubject reproducibility for the diagnosis of reflux disease was 89% for the entire sample. Among subsets, the reproducibility was 93% for the normals and esophagitis patients and 84% for the atypical symptom patients. Total percent time with pH<4 was the single most discriminate pH parameter (85%) and nearly equaled that of the three combined parameters (89%). The intrasubject variability of this parameter was determined by the mean ±2sd of the relative differences between the two test results for all 53 subjects. Total percent time with pH<4 may vary between tests by a factor of 3.2-fold or less (218% higher to 69% lower). We conclude: (1) ambulatory 24-hr esophageal monitoring is a reproducible test for the diagnosis of gastroesophageal reflux disease; and (2) the large intrastudy variability in 24-hr total acid exposure may limit this test's usefulness as a measurement of therapeutic improvement.Supported, in part, by Public Health Services Grant AM 34200-01A1 from NIADDIK.     

Pharmacologic management and treatment of gastroesophageal reflux disease

Gastroesophageal reflux disease (GERD) is one of the most common diagnoses in daily practice. Diagnosis can be made on symptom evaluation, on pH-monitoring or on endoscopic findings. In contrast to commonly held opinion there is no strong evidence that lifestyle factors are a dominant factor in the pathophysiology of GERD. The various agents currently used for treatment of GERD include mucoprotective substances, antacids, H(2)-blockers and proton pump inhibitors. This article gives an overview of the pharmacological management of GERD and focuses on the differential therapy of endoscopy-negative GERD, GERD with esophagitis and maintenance therapy.     

An experimental model for the study of transient lower oesophageal sphincter relaxation and motor function of the proximal stomach in humans

A simple and reliable experimental model would be useful in human research on new drugs which target transient lower oesophageal sphincter (LOS) relaxation. The aim was to investigate the effect of repeated distensions on the rate of transient LOS relaxation, LOS pressure and motor function of the proximal stomach. Twelve healthy subjects were studied with a multilumen manometric assembly incorporating a sleeve sensor for the LOS and a bag positioned in the proximal stomach and connected to a barostat. Intrabag volume was set at 75% of the threshold for gastric discomfort and maintained for two 30-min distension periods separated by a 45-min washout with the bag deflated. The studies lasted 145 +/- 2 min. The rate of transient LOS relaxations was similar during the two distensions, 3.5;2-4 vs 3;2.5-4 (median;interquartile range) and so was LOS pressure. Baseline intrabag pressure, as a measure of gastric tone, and the number of pressure waves, as a measure of phasic contractions, were also similar, 11.3;9.3-12.3 mmHg vs 10.8;9.3-12.5 mmHg and 16;13-28 mmHg vs 19;15-29 mmHg, respectively. Our model allows to perform 1-day studies which can assess two experimental conditions on transient LOS relaxations and motor function of the proximal stomach within an acceptable time span.     

A model of sterile vesicoureteric reflux in the sheep

Eighteen Coopworth ewe lambs were divided into three groups based on the initial cystourethrogram and cystometry findings at 5 – 7 weeks of age: group 1, 6 lambs with spontaneous low-pressure bilateral vesicoureteric reflux (VUR) on bladder filling were used to study the natural history of reflux; group 2, 5 lambs with no VUR detected were used to establish an experimental model of bilateral VUR using an unroofing surgical procedure; group 3, 7 lambs with spontaneous VUR detected during micturition had the same surgical procedure to increase the degree of VUR. All three animal groups were followed for 4 – 10 months. Spontaneous VUR was demonstrated in 13 of 18 lambs (25/36 ureters). The presence and severity of spontaneously occurring reflux in group 1 lambs diminished with increasing age. VUR was created successfully in group 2 and increased in degree in group 3 animals. The only significant histological finding in all three animal groups with grades II and III VUR was distal renal tubular dilatation. The sheep is a useful and readily available animal for studying VUR. During 4 – 10 months of follow-up, sterile reflux without bladder outflow obstruction resulted in distal renal tubular dilatation, but no renal parenchymal damage. Received April 17, 1997; received in revised form August 5, 1997; accepted August 21, 1997