Abnormalities of gastrointestinal motility in children with nonulcer dyspepsia and in children with gastroesophageal reflux disease

In 11 children (mean age 44.2 months) with symptoms suggesting upper intestinal dysfunction (nonulcer dyspepsia), in nine children (mean age 27.3 months) with gastroesophageal reflux (GER) disease, and in seven controls (mean age 20.4 months) we investigated fasting [for 3 hr or until two migrating motor complexes (MMC) were observed] and fed (90 min) antroduodenal motility by means of perfused catheter system; furthermore, we measured both gastric emptying of a radiolabeled milk formula and fasting duodenogastric reflux during manometry by assessing bile salt concentration in gastric aspirates. No structural abnormalities of gastrointestinal tract and organic disorders were detected in the patients. In a high proportion of both groups of patients we found manometric abnormalities of interdigestive and fed motor patterns that were not seen in the controls: absence of antral phase III of MMC; significant decrease of antral and/or duodenal motor activity during fasting and/or fed periods; abnormal propagation or configuration of MMC phase III that was signficantly shorter than in controls; bursts of sustained fasting and/or fed phasic duodenal activity, frequently uncoordinated with adjacent gut segments. When compared to controls, the mean intragastric concentration of bile salts during all MMC phases and the mean 1-hr percent gastric activity of the radiolabeled milk were significantly higher in the two groups of patients. We conclude that in a high proportion of children with nonulcer dyspepsia and of children with GER disease, gastrointestinal manometry may reveal significant irregularities of antral and duodenal motility, which are associated with increased duodenogastric reflux and delayed gastric emptying.     

Achalasia and other diseases associated with disorders of gastrointestinal motility

The aetiology of achalasia is unknown, but it has been suggested that it is congenital in origin and associated with such disorders as infantile pyloric stenosis or Hirschsprung's disease. Another reported association has been with Hodgkin's disease. A survey of 126 patients with achalasia, and their first degree relatives was undertaken to record the prevalence of infantile pyloric stenosis, Hirschsprung's disease and Hodgkin's disease. The prevalence of motor neurone disease and diabetes, which can be associated with motility disorders of the oesophagus, were also recorded as a measure of the efficiency of the questionnaire. None of the 126 patients with achalasia suffered from pyloric stenosis, Hirschsprung's disease, Hodgkin's lymphoma or motor neurone disease. There was no increased frequency of these disorders amongst first degree relatives. There appears to be no common aetiology for aganglionic bowel disease, and no obvious association between Hodgkin's disease and achalasia. Diabetes is seen with the expected frequency amongst patients with achalasia and their relatives, indicating the adequacy of the questionnaire.     

Disorders of gastrointestinal motility associated with diabetes mellitus

Gastrointestinal symptoms such as vomiting, constipation, diarrhea, and fecal incontinence occur frequently in patients with diabetes mellitus. In a survey of 136 diabetic outpatients, 76% had one or more gastrointestinal symptoms, the commonest symptom being constipation (found in 60%). In many cases these symptoms are thought to be due to abnormal gastrointestinal motility that, in turn, may be a manifestation of diabetic autonomic neuropathy involving the gastrointestinal tract. The pathophysiology of these gastrointestinal symptoms, clarified in recent studies, and the clinical features and treatment of these problems in diabetic patients are reviewed.     

Functional lumen imaging probe in gastrointestinal motility diseases

Dysfunction of gastrointestinal (GI) sphincters, including the lower esophageal sphincter (LES) at the esophagogastric junction (EGJ) and the pyloric sphincter, plays a vital role in GI motility disorders, such as achalasia, gastroesophageal reflux disease (GERD), gastroparesis, and fecal incontinence. Using multi‐detector high‐resolution impedance planimetry, the functional luminal imaging probe (FLIP) system measures simultaneous data on tissue distensibility and luminal geometry changes in the sphincter in a real‐time manner. In this review we focus on the emerging data on FLIP, which can be used as an innovative diagnostic method during endoscopic or surgical procedures in GI motility disorders. Subsequent large, prospective, standardizing studies are needed to validate these findings before it can be put to routine clinical use.     

Gut hormones and gastrointestinal motility in children with cystic fibrosis

Intestinal dysmotility may be an important factor contributing to various gastrointestinal complications associated with cystic fibrosis. Motilin, enteroglucagon, neurotensin, and peptide YY may each play a role as endocrine hormones influencing gastrointestinal motor activity. Fasting children with cystic fibrosis (N=8) and controls (N=18) received a liquid nutrient test meal (fat 4 g/100 ml, protein 4 g/100 ml, carbohydrate 20 g/100 ml, 125 kcal/100 ml; 200 ml/m²) containing lactulose (5 g/100 ml), and the plasma concentrations of these peptides were studied. Mouth-to-cecum transit time was simultaneously studied using the breath H₂ technique. Fasting levels of peptide YY and the postprandial response of all four peptides were significantly increased in those with cystic fibrosis. In repeat studies on those with cystic fibrosis after a period of altered pancreatic enzyme supplementation, no significant changes in peptide concentrations were observed. A rise in breath H₂ permitting estimation of mouth-to-cecum transit time was noted in 17 control subjects (70–220 min, median 140). In contrast, a rise occurred in only two with cystic fibrosis after low-dose enzyme (70 and 180 min), and four after high-dose enzyme replacement (120–230 min, median 155). Altered gut hormone secretion may play a role in the pathophysiology of intestinal dysmotility in patients with cystic fibrosis.     

氧化应激在糖尿病胃肠动力障碍中的作用

糖尿病胃肠动力障碍是糖尿病常见的并发症,其机制尚未明确。近年来,越来越多的证据表明,氧化应激与糖尿病及其并发症的发生、发展密切相关。本文就氧化应激在糖尿病胃肠动力障碍中的作用作一概述。     

Abnormalities in IgA and IgM are associated with treatment-resistant ITP

We hypothesized that immune dysregulation, as represented by abnormal immunoglobulin (Ig) levels, may increase immune thrombocytopenia (ITP) severity. A cross-sectional analysis was performed encompassing patients with ITP seen at the New York Presbyterian Platelet Disorder Center in the past 10 years. The subjects' Ig levels were measured, and subjects were analyzed for differences in treatment response. Subjects with an IgA level greater than median had a significantly increased chance of failing to respond to standard treatment (steroids, intravenous Ig, and intravenous anti-D) than did subjects with an IgA level lower than median (37 of 271, 14%; vs 22 of 281, 8%; P = .03) and an increased risk for bleeding (36 of 378, 10%; vs 19 of 386, 5%; P = .02). Subjects with an IgM less than 56 (lower limit of normal) failed to respond to standard treatment more often than patients with a normal IgM (12 of 67, 18%; vs 44 of 467, 9%; P = .05) with a trend toward worsened response to splenectomy (3 of 18, 17%; vs 36 of 86, 42%; P = .06). These observations suggest that immune dysregulation, as represented by elevations in IgA or decreased levels of IgM, are associated with ITP that is more resistant to treatment.     

Hyposelenaemia: patients with gastrointestinal diseases are at risk

A retrospective study of serum selenium determinations performed in a hospital laboratory revealed 47 cases of hyposelenaemia (defined as a serum selenium level below 0.74 mumol l-1). Moderate hyposelenaemia (serum selenium 0.30-0.55 mumol l-1) was found in 11 patients and seven of these suffered from gastrointestinal diseases. Furthermore severe hyposelenaemia (serum selenium below 0.30 mumol l-1) was detected in three patients, who were all affected by gastrointestinal disease. We concluded that patients with gastrointestinal diseases are especially at risk of developing selenium deficiency and should be monitored by repeated determinations of serum selenium. Patients with moderate or severe hyposelenaemia should receive selenium treatment.     

Effect of erythromycin on antroduodenal motility in children with chronic functional gastrointestinal symptoms

To evaluate the effects of erythromycin on antroduodenal motility in children with chronic functional gastrointestinal symptoms, we studied 35 consecutive subjects referred for diagnostic motility studies. We recorded fasting motility for >4 hr, then infused in random order either 1 or 3 mg/kg erythromycin intravenously over 1 hr and continued the study for another hour. Erythromycin induced phase III in 18 of 20 children who had phase III during fasting compared to only one of 15 who did not (P<0.001). The antral motility index increased after erythromycin (1596±323 vs 436±242 mm Hg/30 min before erythromycin,P<0.005) but the duodenal motility index did not change. The antral motility index was greater in children receiving 3 mg/kg than in those receiving 1 mg/kg (1968±391 vs 1226±285 mm Hg/30 min,P<0.01), but duodenal motility indices did not differ. Only one child receiving the lower dose erythromycin complained of abdominal pain, nausea, or vomiting vs 9 of 19 the children receiving the higher dose (P<0.02). In summary, in children with chronic functional gastrointestinal disorders, erythromycin rarely induced phase III in patients who did not have it during fasting. When different doses erythromycin are compared, 1 and 3 mg/kg are equally efficacious in inducing phase III episodes; the lower dose is associated with fewer side effects and the higher dose produces a higher antral motility index.     

Future perspectives on infections associated with gastrointestinal tract diseases

There are a vast number of infectious agents that are associated with gastrointestinal (GI) tract diseases. The epidemiology of GI diseases is changing, with a greater number of conditions increasing in incidence. Challenges exist with establishing cause-and-effect relationships because of the ubiquitous nature of these organisms and the milieu in which they exist. Advances in technology should provide novel methods for identifying and diagnosing these organisms and the relationship they have with a specific digestive disease.     

Use of Clostridium botulinum toxin in gastrointestinal motility disorders in children

More than a century has elapsed since the identification of Clostridia neurotoxins as the cause of paralytic diseases. Clostridium botulinum is a heterogeneous group of Gram-positive, rod-shaped, spore-forming, obligate anaerobic bacteria that produce a potent neurotoxin. Eight different Clostridium botulinum neurotoxins have been described(A-H) and 5 of those cause disease in humans. These toxins cause paralysis by blocking the presynaptic release of acetylcholine at the neuromuscular junction. Advantage can be taken of this blockade to alleviate muscle spams due to excessive neural activity of central origin or to weaken a muscle for treatment purposes. In therapeutic applications, minute quantities of botulinum neurotoxin type A are injected directly into selected muscles. The Food and Drug Administration first approved botulinum toxin(BT) type A in 1989 for the treatment of strabismus and blepharospasm associated with dystonia in patients 12 years of age or older. Ever since, therapeutic applications of BT have expanded to other systems, including the gastrointestinal tract. Although only a single fatality has been reported to our knowledge with use of BT for gastroenterological conditions, there are significant complications ranging from minor pain, rash and allergic reactions to pneumothorax, bowel perforation and significant paralysis of tissues surrounding the injection(including vocal cord paralysis and dysphagia). This editorial describes the clinical experience and evidence for the use BT in gastrointestinal motility disorders in children.     

Treatment of iron deficiency anemia associated with gastrointestinal tract diseases

The gastrointestinal (GI) tract is a common site of bleeding that may lead to iron deficiency anemia (IDA). Treatment of IDA depends on severity and acuity of patients’ signs and symptoms. While red blood cell transfusions may be required in hemodynamically unstable patients, transfusions should be avoided in chronically anemic patients due to their potential side effects and cost. Iron studies need to be performed after episodes of GI bleeding and stores need to be replenished before anemia develops. Oral ...     

Training in gastrointestinal motility

Gastrointestinal (GI) motility and functional GI disorders are common reasons for patients to see gastroenterologists. Knowledge of the evaluation and treatment of these disorders is important to appropriately care for these patients in clinical practice. Training in GI motility is important to GI fellows and their subsequent role as gastroenterologists. The aim of this paper is to discuss the importance of GI motility disorders for trainees in gastroenterology, provide some suggestions for training activities for GI fellows in GI motility, and discuss ways to address the unmet clinical need for caring for patients with GI motility disorders that gastroenterologists routinely see in their clinical practice.     

Abnormalities of upper gut motility in patients with slow-transit constipation.

OBJECTIVE: To further delineate motor activity of the upper gastrointestinal tract in patients with slow-transit constipation. DESIGN: A prospective study comparing healthy volunteers with patients with a clinical diagnosis of slow-transit constipation. METHODS: Eighteen patients with clinical diagnosis of slow-transit constipation and 10 healthy controls were included in the study. Fasting antroduodenal motility was measured by perfusion manometry for at least one complete cycle of the migrating motor complex or a maximum of 300 min. Oesophageal manometry, gastric emptying and orocaecal transit time measurements were also performed. RESULTS: At least one complete cycle of the migrating motor complex was observed in all controls, but in only nine patients (P < 0.01 versus control). The migrating motor complex cycle was incomplete (n = 5) or phase 3 activity was absent (n = 4) in the other patients. The incidence of clustered contractions was significantly increased in slow-transit constipation (P = 0.05 versus controls). The area under the contraction curve during late phase 2 (1509+/-296 mmHg x s) in patients with a complete cycle was significantly smaller than that in controls (2997+/-614 mmHg x s; P = 0.05). Orocaecal transit time was not significantly different among patients and controls, but oesophageal motility was abnormal in five of 18 patients and gastric emptying was abnormal in eight of 15 patients. CONCLUSION: Abnormalities of upper gut motility occur frequently in patients with slow-transit constipation. Interdigestive antroduodenal motility is characterized by (i) absence or prolonged duration of the migrating motor complex, (ii) an increased number of clustered contractions, or (iii) a decreased motility during late phase 2 of the migrating motor complex.     

Effect of hemorrhagic shock on oxidative phosphorylation and blood flow in rabbit gastrointestinal mucosa

The pathophysiologic mechanism responsible for ulceration of gastric fundus and corpus mucosa following hemorrhagic shock is not well defined. We examined the effect of hemorrhagic shock (25 ml blood/kg) and resuscitation (reinfusion of shed blood) on oxidative phosphorylation in different tissues of the rabbit to determine if differences in mitochondrial response to hemorrhagic shock and resuscitation contribute to the propensity of gastric fundus and corpus to necrose before other tissues. Blood flow was measured by using radioisotope-labeled microspheres to determine if changes in regional blood flow could be correlated with this propensity to ulcerate. The respiratory control index (RCI), an index of the integrity of mitochondrial function, was significantly increased in gastric antrum, liver, and kidney from the animals subjected to hemorrhagic shock and successful resuscitation when compared to control animals. In liver and kidney, these differences were largely due to increases in state 3 respirations. Duodenal and gastric corpus and fundus mitochondria showed no differences in RCI between bled and control groups. Blood flow data did not implicate ischemia as the mechanism responsible for the differential rate of ulceration after hemorrhage. The inability of fundus, corpus, and small-bowel mucosal mitochondria to respond to the stress of hemorrhagic shock and resuscitation in a manner similar to liver, kidney, and gastric antral mitochondria may place these tissues at greater risk to ulcerate. Further work is necessary to define whether this difference in mitochondrial response patterns represents a real increase in the maximal respiratory capacity of liver, kidney, and antrum after shock and resuscitation.     

Abnormal gastrointestinal motility in patients with celiac sprue

No study to date has objectively investigated whether the motor behavior of the small bowel is abnormal in celiac sprue. The purpose of this study was to systematically address this topic by means of intraluminal pressure recordings in a series of such patients. Sixteen subjects (nine adults, seven children, age range 2–69 years) with celiac sprue were recruited and studied while untreated. Manometric examination was carried out for 6 hr during fasting and 3 hr after a meal. Adult celiac patients displayed a significantly (mean ±sem) greater frequency of migrating motor complexes in comparison to controls during fasting (4.44±1.6 vs 2.45±0.20,P<0.01), whereas no differences were found in the pediatric group with respect to this variable. Fasting motor abnormalities, chiefly represented by discrete clustered contractions, giant jejunal contractions, and bursts of nonpropagated contractions, were discovered in a high percentage in both groups of celiac subjects (89% in adults and 44% in children, respectively). Similar abnormalities were observed in the postprandial period, especially in adults. In conclusion, patients with celiac sprue frequently display discrete gastrointestinal motor abnormalities, which though perhaps nonspecific may account for several symptoms complained of by such patients.