Symposium on diarrhea. 5. Postoperative diarrhea.

Under normal circumstances many physiologic mechanisms prevent diarrhea. The most important are the normal processes of gastric emptying, digestion and absorption, the functioning of the ileocecal valve and elimination of bacteria from the small bowel. A surgical procedure may disrupt any of these mechanisms or may unmask a previously asymptomatic disorder that now requires appropriate treatment. Treatment of diarrhea related to surgery may be directed toward the diarrhea itself with such agents as tranquilizers and opiates but if these are not soon effective any disrupted functions must be analysed and specific measures taken to correct or compensate for these disruptions. The most useful measures in appropriate cases are the prevention of the dumping syndrome and the administration of pancreatic enzymes, cholestyramine, hydrophilic stool thickeners and broad-spectrum antibiotics. These measures may be ineffective or inadequate and surgical revision may be necessary.     

Symposium on diarrhea. 3. Investigation of chronic diarrhea.

The practical approach to the investigation of diarrhea must be logical and based on anatomic considerations. The site of the underlying disorder may be determined by the clinical picture, and the logic of investigation will be influenced by the history. Important specific investigation in a case of colonic diarrhea include a careful rectal examination, stool inspection, sigmoidoscopy, rectal biopsy and barium enema study. Colonoscopy has been used, but its role has yet to be defined. In a case of small-bowel steatorrhea or diarrhea quantitative chemical estimation of the daily output of stool fat is useful, and to this investigation is added a small-bowel radiograph series and, if the radiographic findings are abnormal, small-bowel biopsy. Other investigations for small-bowel disease may include the breath test with carbon-14-labelled glycocholic acid, the lactose tolerance test, duodenal aspiration for giardiasis, analysis of serum immunoglobulins and, on occasion, isolation of vasoactive intestinal polypeptide hormone (which may aid the diagnosis of functioning tumours of the pancreas or small bowel). Investigations for pancreatic steatorrhea include abdominal radiography, performance of the secretin test and testing of the response to pancreatic replacement therapy. In some patients it may be useful to use endoscopic retrograde cholangiopancreatography to differentiate pancreatic carcinoma and chronic pancreatitis.     

肠道菌群与腹泻型肠易激综合征 相关性的研究进展

肠易激综合征(IBS)是一种常见的功能性胃肠道疾病,其特征是反复发作的腹痛,伴随排便频率与大便性状的改变。腹泻为主的肠易激综合征(IBS-D)是其主要亚型,主要表现是腹痛和腹泻。目前IBS-D的发病机制尚不完全明确,但大量的研究提示可能与胃肠道动力紊乱、黏膜通透性和肠上皮屏障功能改变、内脏高敏感性增加、"脑-肠-菌"轴失调、肠道感染与炎症反应激活、精神心理因素异常等有关。随着研究的不断深入,发现肠道菌群与IBS-D的关系密切,调节肠道菌群的益生菌干预成为缓解IBS-D相关症状的手段之一。本研究就近十余年来肠道菌群情况与IBS-D关系的研究现状作一综述。     

Symposium on diarrhea. 2. Clinical diagnosis of the causes of diarrhea.

Elucidation of the cause of diarrhea is facilitated by considering which of three principal determinants are of relevance in a particular case. These determinants relate to the onset (whether diarrhea is acute or chronic), to infection or an absence ofinfection and to the presence in the stool of blood or mucus, or both. Diagnosis is also facilitated by taking an accurate and full history, conducting a physical examination, performing sigmoidoscopy and, with proper care, attempting a therapeutic diagnosis. Findings from investigations should then enable one to arrive at a diagnosis. The diagnosis can be reached in an orderly fashion by classifying the types of diarrhea into eight categories: with respect to the acute or chronic onset a case of diarrhea may be noninfectious, without blood or mucus in the stool; noninfectious, with blood or mucus, or both; infectious, without blood or mucus; and infectious, with blood or mucus in the stool.     

婴幼儿腹泻病原学及其快速诊断

目的探讨小儿腹泻标本病原学特点及流行病学特征,寻求小儿感染性腹泻的快速诊断方法。方法对我院2003年10月至2005年9月门诊及住院的1160例2个月-5岁腹泻患儿的腹泻标本进行细菌学检查及pH检测。结果(1)1160例患儿腹泻标本病原学阳性605例(52.16%),检出病原20种621株,外源性肠道病原菌、内源性肠道条件致病菌以及轮状病毒3种病原构成比依次为35.75%、32.69%、31.56%。主要病原:(1)轮状病毒196株(31.56%),志贺菌118株(19.00%),克雷伯菌86株(13.8%),枸橼酸杆菌67株(10.79%),致泻性大肠埃希菌60株(9.66%)。(2)1160例患儿腹泻标本6个月-2岁患儿占881例(69.91%)。轮状病毒腹泻多发于秋冬季、大便为水样、多见于2岁以内婴幼儿,志贺菌以夏秋季与脓血便检出率较高。(3)病原菌分离阳性腹泻标本pH>7占明显优势,轮状病毒阳性标本、病原检查阴性标本、健康体检对照标本pH<6占明显优势,前者pH与后三者pH统计学比较,差异有高度显著性(P<0.01)。结论引起小儿腹泻的病原种类繁多,轮状病毒居首位,内源性肠道条件致病菌在腹泻标本中的构成比已接近外源性肠道致病菌而成为腹泻的重要病原菌,大便pH可作为急性腹泻病早期简单、快速、准确、价廉的初步诊断及合理应用抗生素的重要指标。     

Constipation and catharsis.

Constipation is endemic in the Western world. Stool consistence and associated symptoms are more important than stool frequency. The patient''s attitude towards his bowel habit is also important. Exclusion of "organic" disease, reassurance and discussion of normal variations of bowel habit are necessary first steps in treatment. Adquate bulk in the stool must be ensured, either through diet or bulking agnets, and bowel retraining attempted. Laxatives should be reserved for episodes of constipation following enforced bedrest, or as a preparation for diagnostic procedures. Long-term use should be avoided.     

凝结芽胞杆菌活菌片对实验性腹泻小鼠的治疗作用

目的 观察凝结芽胞杆菌活菌片对氨苄青霉素钠诱发的小鼠腹泻的治疗作用。方法利用氨苄青霉素钠口服诱发小鼠实验性腹泻和肠道菌群失调,然后用凝结芽胞杆菌活菌片,口服,每天2次,共4d,观察治疗后的小鼠排便和肠道菌群变化。结果在各给药组中,治疗第1天有70％～85％的小鼠排正常便,生理盐水组只有10％排正常便（P〈0．01）;治疗第2天给药组中有80％～90％的小鼠排正常便,生理盐水组仅为50％（P〈0．01）。肠道菌群分析结果表明,凝结芽胞杆菌在治疗第2天开始定植,停药第7天后逐渐消失,定植期为10d左右。在各给药组中,治疗第2天肠道菌群开始恢复,第4天均升高到正常,而生理盐水组的恢复比各给药组显著的慢（P〈0．01）。结论 凝结芽胞杆菌活菌片对小鼠实验性腹泻有明显的止泻作用,并能加速肠道菌群的恢复。     

Cryptosporidiosis: a cause of summer diarrhea in children

Recent studies have suggested that some outbreaks of diarrhea in children may be caused by Cryptosporidium, a parasite associated with gastrointestinal and respiratory tract infection in animals. In a study of 7300 British Columbia patients with diarrhea, cryptosporidial oocysts were found in the stool samples of 46 (0.63%). It appears that the occurrence of cryptosporidiosis is related to three factors: the patient''s age, the time of year and the geographic location.     

Pathogenesis of rotavirus diarrhea.

Rotavirus diarrhea is a major cause of infantile gastroenteritis worldwide. This review is mainly devoted to the effects of Rotavirus on intestinal epithelial transport and to the pathophysiological mechanisms proposed to underlie the intestinal fluid secretion caused by the virus.     

Gluten-sensitive enteropathy in a cynomolgus monkey

A malabsorption syndrome was observed in a cynomolgus macaque. Clinical signs included weight loss despite increased appetite, and diarrhea, characterized by an increased volume of soft, tan, malodorous feces. Clinicopathologic findings included hypoalbuminemia, generalized dilation of bowel loops with a prolonged transit time, steatorrhea and markedly diminished absorption of D-xylose. Biopsies of the duodenum and jejunum had total villous atrophy, crypt hyperplasia and a plasmacytic-lymphocytic infiltrate of the lamina propria. The monkey's diet was changed to a semi-synthetic diet containing no grain products. Subsequently, stool characteristics, body weight and intestinal villous morphology returned to normal. This response to removal of grain products from the diet suggests a syndrome similar to gluten-sensitivity enteropathy in human beings.     

Effects of a high semen-collection frequency on the quality of sperm from ejaculates and from six epididymal regions in boars

This study examines the effect of semen-collection rhythm on the sperm maturation process in boar epididymis. Three post-pubertal boars were submitted to a high semen-collection frequency (stressed boars) during 4 days, and three males were kept as a control group (control boars). Semen samples coming from six epididymal regions and from the ejaculate of each male were evaluated for sperm concentration, sperm vitality, sperm motility and sperm morphology. In each epididymal region, either fluid resorption or fluid secretion was determined from the variation in sperm concentration. The pattern of fluid resorption-secretion along the epididymal duct differed significantly between the stressed and control boars. A high semen-collection frequency also affected the development of sperm motility and the sperm cytoplasmic droplet displacement along the epididymal duct. The incidence of some sperm abnormalities was also found to be higher in some epididymal regions and ejaculates of stressed boars. From the results of this study, it can be concluded that a high semen-collection frequency brings about an altered resorption and secretion pattern of the epididymal fluid, which results in defective sperm maturation and abnormal development of sperm motility.     

Impacts of peripheral obestatin on colonic motility and secretion in conscious fed rats

Obestatin, a novel putative 23-amino acid peptide, was found to be derived from a mammalian preproghrelin gene by using a bioinformatics approach. Although the effects of obestatin on food intake and upper gut motility remain controversial, no studies have been carried out to explore its influence on lower gut motility and secretion. We investigated the impacts of intravenous (IV) injection of obestatin on rat colonic motor and secretory functions. Colonic transit time, fecal pellet output, and fecal content were measured in freely fed, conscious rats, which were chronically implanted with IV and colonic catheters. To test the validity of this animal model, human/rat corticotropin-releasing factor (h/rCRF) served as a stimulatory inducer of colonic motility and secretion. IV injection of obestatin (45, 100, and 300nmol/kg) did not affect the colonic transit time, whereas IV injection of h/rCRF (30nmol/kg) effectively accelerated colonic transit time. IV obestatin, in every dose we tested, also did not modify fecal pellet output, frequency of watery diarrhea, total fecal weight, fecal dried solid weight, or fecal fluid weight in the first hour after injection. On the other hand, IV injection of h/rCRF significantly enhanced fecal pellet output, as well as increased the frequency of watery diarrhea, total fecal weight, fecal dried solid weight, and fecal fluid weight during the first hour after injection compared with IV saline controls. In conclusion, peripheral obestatin administration has no impact on colonic motility and secretion in conscious fed rats.     

Steatorrhea in patients with liver disease

Intestinal function was studied in 26 patients with seven types of acute and chronic liver disease, documented by liver biopsy. Steatorrhea, defined by a stool fat higher than 6 g. per day, was present in 18 of 23 consecutive patients studied, an incidence of 78.3%. Two patients with infectious hepatitis associated with steatorrhea studied previously were added and the 20 cases were analyzed. The malabsorption found was confined to fat and fat-soluble vitamins; stool excretion varied from 6.1 to 22 g. per day in the seven groups studied. No histological abnormality was seen on jejunal biopsy, serum vitamin B₁₂, D-xylose and Schilling tests were normal, and no radiological findings associated with malabsorption were detected in the small bowel. It is concluded that steatorrhea is a common finding in a wide variety of acute and chronic liver diseases and cannot be attributed to a primary defect of the small bowel.     

酪酸梭菌活菌散联合葡萄糖酸锌治疗儿童急性腹泻的疗效观察

目的探讨酪酸梭菌活菌散联合葡萄糖酸锌治疗儿童急性腹泻的疗效。方法选取急性腹泻患儿76例,随机分为观察组和对照组各38例。两组患儿均予以调整饮食、口服或静脉补液和纠正水电解质酸碱失衡紊乱等常规治疗。观察组患儿予以酪酸梭菌活菌散和葡萄糖酸锌联合治疗,对照组患儿予以单纯酪酸梭菌活菌散治疗。观察两组患儿治疗后主要症状和体征改善的时间,并比较其临床疗效及治疗后3个月内腹泻的复发率。结果观察组患儿治疗后的止泻、呕吐、腹痛和粪常规等恢复正常时间均明显短于对照组（P〈0.05）;同时治疗3 d后,观察组患儿临床总有效率为94.74%,明显高于对照组的78.95%（χ2=4.15,P〈0.05）。两组患儿治疗后随访3个月,其中观察组和对照组分别腹泻复发5例（13.16%）和13例（34.21%）,观察组腹泻的复发率明显低于对照组（χ2=4.66,P〈0.05）。结论酪酸梭菌活菌散联合葡萄糖酸锌治疗儿童急性腹泻的疗效较肯定,能明显改善患儿腹泻症状,缩短腹泻病程,并能减少腹泻的复发。     

Interruption of transmembrane signaling as a novel antisecretory strategy to treat enterotoxigenic diarrhea.

Bacteria that produce heat-stable enterotoxins (STs), a leading cause of secretory diarrhea, are a major cause of morbidity and mortality worldwide. ST stimulates guanylyl cyclase C (GCC) and accumulation of intracellular cyclic GMP ([cGMP]i), which opens the cystic fibrosis transmembrane conductance regulator (CFTR)-related chloride channel, triggering intestinal secretion. Although the signaling cascade mediating ST-induced diarrhea is well characterized, antisecretory therapy targeting this pathway has not been developed. 2-ChloroATP (2ClATP) and its cell-permeant precursor, 2-chloroadenosine (2ClAdo), disrupt ST-dependent signaling in intestinal cells. However, whether the ability to disrupt guanylyl cyclase signaling translates into effective antisecretory therapy remains untested. In this study, the efficacy of 2ClAdo to prevent ST-induced water secretion by human intestinal cells was examined. In Caco-2 human intestinal cells, ST increased [cGMP]i, induced a chloride current, and stimulated net basolateral-to-apical water secretion. This effect on chloride current and water secretion was mimicked by the cell-permeant analog of cGMP, 8-bromo-cGMP. Treatment of Caco-2 cells with 2ClAdo prevented ST-induced increases in [cGMP]i, chloride current and water secretion. Inhibition of the downstream consequences of ST-GCC interaction reflects proximal disruption of cGMP production because 8-bromo-cGMP stimulated chloride current and water secretion in 2ClAdo-treated cells. Thus, this study demonstrates that disruption of guanylyl cyclase signaling is an effective strategy for antisecretory therapy and provides the basis for developing mechanism-based treatments for enterotoxigenic diarrhea.     

雌性生殖道碳酸氢根分泌机制及其对精子受精能力的影响

雌性生殖道内微环境对精子获得受精能力所依赖的一系列分子事件起关键性作用。研究表明,雌性生殖道含有高浓度的碳酸氢根,而且已经证明此阴离子对精子功能(包括精子运动,精子获能,超激活运动以及顶体反应)起重要的作用。本综述详细总结了雌性生殖道内微环境碳酸氢根对精子功能的影响及其分子机制,并探讨子宫内碳酸氢根的分泌机制。同时对碳酸氢根分泌受损可能是女性不育的一个病因提供了最新证据。     

Intestinal coccidia in Cuban pediatric patients with diarrhea

From May to August 1999, we evaluated 401 patients from a pediatric hospital of Havana City. One group was composed of 113 patients with diarrhea admitted to the Gastroenterology ward and a second consisted of 288 patients without diarrhea, admitted for other reasons, and hospitalized within the same time period. Three stool samples were collected from each child and were examined using three parasitological techniques. When we compared the frequency of parasite species between both groups, we found Cryptosporidium spp. and Cyclospora cayetanensis, only in the group of children with diarrhea (P < 0.01). However, no significant differences were found in the occurrence of the other intestinal parasites (P > 0.05). In addition, in those children infected with Cryptosporidium, the diarrhea had a more prolonged duration (P < 0.01), while those infected with Cyclospora, the abdominal cramps or pain, and acute diarrhea were more frequently detected (P < 0.01). Our results showed that emerging intestinal coccidia are pathogens strongly associated in this group of children with diarrhea.     

复方嗜酸乳杆菌片对感染性腹泻患者胃肠道症状的影响

目的应用复方嗜酸乳杆菌片治疗感染性腹泻,观察微生态制剂对患者胃肠道症状的影响。方法选择100例感染性腹泻患者,均来自青岛大学附属中心医院,采用随机数字表法随机分为A、B组。其中A组患者(80例)单用复方嗜酸乳杆菌片(1.0g/次,3次/d,口服)治疗;B组患者(20例)单用利福昔明片(0.2g/次,4次/d,口服)治疗。两组患者均采用配对设计方法,治疗前进行胃肠道症状分级评分,包括单个症状(腹痛、腹胀、腹泻频率、大便性状)的评分和上述症状的总评分。治疗3d后门诊随访或电话随访,再次进行胃肠道症状分级评分,比较治疗前后患者的胃肠道症状评分改善情况并判断疗效以及治疗中的不良反应。结果两组患者的总有效率分别为78.75%和85.00%,差异无统计学意义(P0.05)。两组患者治疗过程中均未见不良反应。复方嗜酸乳杆菌片治疗后患者腹胀、腹泻频率、大便性状的症状评分和症状总评分较治疗前显著降低,差异有统计学意义(P0.01)。腹痛症状评分治疗前后差异无统计学意义(P0.05)。结论复方嗜酸乳杆菌片治疗感染性腹泻能达到满意的疗效,可改善患者腹胀、腹泻频率、大便性状等胃肠道症状。     

Regulation mechanisms of intestinal secretion: implications in nutrient absorption

Intestinal secretion is a normal phenomenon, indispensible to solubilize and dilute nutrients and to maintain fluidity in the intestinal lumen. Enterotoxins and certain drugs may disrupt the proabsorptive status maintained by the small intestine under physiologic conditions. Hormones found in nervous and specialized intestinal enterochromaffin cells are responsible, in part, for secretion of fluid into the lumen. Afferent vagal nerve impulses mediated by 5-hydroxytryptamine (serotonin; 5-HT), vasoactive intestinal peptide (VIP) and substance P are the major agents of secretory stimulation. Toxins from pathogenic bacteria, especially some strains of E. coli and V. cholerae, trigger a secretory response and a chain of events involving cGMP and cAMP which result in chloride secretion, coupled to sodium and fluid efflux into the lumen. If secretion is unchecked by natural mechanisms or medications, the consequences are diarrhea, with potential dehydration, hyponatremia and ultimately death. Introduction of absorbable nutrients in the intestinal lumen has a major antisecretory action, both by a nutrient-gene interaction and by proabsorptive hormone expression. In additon, during the absorptive process water is carried into the enterocyte together with solutes. Hydrolysis-resistant peptides of dietary origin and ingested soluble fiber may also have a proabsorptive effect. The gastrointestinal system has a variety of antisecretory or proabsorptive hormonal and protein agonists that balance the outflow of fluid and electrolytes. The more extensively studied are neuropeptide Y/peptide YY (NPY/PYY) and the antisecretory factor (AF). Nitric oxide (NO), a short-lived second messenger, has a major role in secretion by activating cGMP. The intracellular concentration of NO may regulate the absorptive/secretory status of the small intestine, either stimulating absorption or inducing secretion. Specifically targeted 5-HT receptor antagonist drugs and other pharmacologic agents have been clinically tried for the treatment of severe diarrhea, drug-induced malabsorption and reversal of cellular damage.     

3种模拟中医体征的体虚便秘大鼠模型建立及效果观察

目的：分别建立大鼠血虚、阴虚和阳虚便秘模型并比较其结肠动力、结肠水代谢、结肠黏液分泌和结肠水通道蛋白2（AQP2）的表达水平。方法：40只SD大鼠,雌雄各半,随机分为4组（n=10）：正常对照组（N）、血虚便秘组（XC）、阴虚便秘组（YC）、阳虚便秘组（YAC）。分别采用放血+洛哌丁胺、甲状腺素+洛哌丁胺、冰水刺激+洛哌丁胺建立血虚便秘、阴虚便秘、阳虚便秘大鼠模型,放血每周1次,药物每天灌胃1次,连续42 d。检测大鼠活动状态、体质量、大便性状、口肛传输时间、小肠推进率、粪便和结肠含水量等体征指标,对结肠组织进行AB-PAS染色和免疫组化染色,观察黏液分泌情况和AQP2表达水平。结果：与正常对照组比较,3种模型大鼠体重增长减慢;造模第40天自主活动量变化率由大到小依次为YC、XC和YAC;造模第30天出现固体硬质粪便,粪便评分升高顺序为XC、YC和YAC;口肛传输时间均显著延长、小肠推进率均显著降低（P < 0.05,P < 0.01）,肠动力减低顺序为YC、YAC和XC;粪便含水量均显著减少（P < 0.05,P < 0.01）,XC和YAC组大鼠结肠含水量显著减少（P < 0.05,P <0.01）,YC大鼠结肠含水量有减少趋势,结肠水代谢顺序为YC、YAC和XC;3种模型大鼠结肠黏膜层腺管和杯状细胞出现不同程度缩小,黏液分泌减少,分泌功能障碍顺序为YAC、YC和XC,且近端和远端结肠AQP2的表达均显著增加（P < 0.05,P < 0.01）,增加顺序近端结肠为YAC、YC、XC,远端结肠为YAC、XC和YC。结论：复合因素长期刺激均可建立符合中医体征的便秘大鼠模型,且各模型大鼠结肠运动、结肠水代谢、结肠黏液分泌和AQP2表达水平存在一定的差异。