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Erythromycin increases gastric antral motility in human premature infants.

The aim of this study was to determine if erythromycin (EM), which is a potent motilin agonist, alters gastrointestinal motility in premature infants. Six infants who were born after 23-30 weeks gestation and weighed 825-1,408 g at birth were studied when 6-31 days old. Intraluminal pressure changes within the gastric antrum and proximal duodenum were recorded. We infused EM 0.75 mg/kg intravenously for 15 min and we compared gastric and duodenal contractions for 30 min between before and after the initiation of EM infusion. In these preterm infants the migrating complex was not present, and was not induced by EM. However, in all 6 infants EM increased nonpropagating antral clusters of contractions (p < 0.05). The antral motility index increased 4-fold (p < 0.05). We concluded that human premature infants have functioning motilin receptors.

Duodenum↗

Evaluation of gut motility in type II diabetes by the radiopaque marker method.

BACKGROUND: The clinical usefulness of the radiopaque marker method for detecting diabetic gastrointestinal motility disturbances, was evaluated by examining 21 type II diabetes subjects who did not have any neuropathic symptoms. METHODS: After administration of a Sitzmark capsule, markers were located using plain abdominal radiographs, and the transit time of the markers through seven areas of digestive tract was calculated by Arhan's methods. The plasma concentration of acetaminophen at 45 min after oral administration was measured to evaluate gastric emptying time. The coefficient of variation of R-R intervals on the electrocardiograms (CV(R-R)) was measured to evaluate parasympathetic autonomic function. RESULTS: In the diabetics, the average (+/- SD) transit time through upper digestive tracts was slightly but not significantly elongated compared with control subjects (14.4 +/- 8.3 vs 9.9 +/- 6.1 h). Significant elongation was observed in transit time through the lower digestive tracts or the whole gut (44.6 +/- 20.9 and 57.9 +/- 22.3 h, respectively) compared with control subjects (23.3 +/- 8.5 and 33.2 +/- 11.0 h). The transit time of the markers from stomach to small intestine was highly correlated (r = 0.693) with plasma concentration of acetaminophen. The transit time through either the whole colon (r = 0.564) or the whole gut (r = 0.630) was highly correlated with CV(R-R). CONCLUSIONS: These findings suggest that the radiopaque marker method is a useful tool for detecting the sections of the digestive tract responsible for gut motility disturbances. In type II diabetics with no neuropathic symptoms, the lower digestive tracts may deteriorate prior to the impairment of upper digestive tracts.

Acetaminophen↗

No inhibition of gastro-intestinal propulsion after propofol- or propofol/ketamine-N2O/O2 anaesthesia. A comparison of gastro-caecal transit after isoflurane anaesthesia.

BACKGROUND: Gastrointestinal motility may be considerably reduced by anaesthesia and or surgery resulting in postoperative ileus. Inhibition of propulsive gut motility is especially marked after an opioid-based technique. Little, however, is known of the gastrointestinal effects of the hypnotic propofol when given continuously over a longer period of time, which is the case in total intravenous anaesthesia (TIVA) and in intensive care sedation. We therefore set out to study the effects of a propofol-based nitrous oxide/oxygen anaesthesia (group PO) on gastro-caecal transit time. The results were compared with a propofol-ketamine technique (group PK) and an isoflurane-based anaesthesia (group I; each group n = 20). METHODS: Gastro-caecal transit was determined by measurement of endexpiratory hydrogen concentration (ppm). Following gastral installation of lactulose at the end of the operation, the disaccharide was degraded by bacteria in the caecum, resulting in the liberation of hydrogen which was expired. A 100% increase in endexpiratory hydrogen concentration compared to the preinduction period was considered the end-point of gastro-caecal transit. RESULTS: There was no significant difference with regard to gastro-caecal transit in the three groups of patients. In the propofol group mean gastro-caecal transit was 119 (+/- 50.6 SD) min, in the propofol-ketamine group it was 147 (+/- 57.4 SD) min, and in the isoflurane group transit time was 122 (+/- 48.6 SD) min. CONCLUSION: The data suggest that propofol, even when given as a continuous infusion, does not alter gastrointestinal tract motility more than a standard isoflurane anaesthesia. The data may be particularly relevant to patients who are likely to develop postoperative ileus. They also suggest that in an ICU setting propofol does not alter gut motility more than a sedation technique with the analgesic ketamine.

Adult↗

Comparison of the inhibitory effects of spermine, papaverine and adrenaline upon isolated segments of the rat small intestine.

In the rat isolated duodenal and ileal segments the active baseline force and spontaneous contractile frequency were inhibited by spermine; the relative potencies, estimated as an ED50, were adrenaline papaverine spermine. The changes in baseline force, but not frequency, due to spermine were sensitive to increased calcium. The duodenum was always more sensitive to papaverine and adrenaline, but the relative sensitivities of the duodenum and ileum were essentially equal for spermine. Inasmuch as the gastrointestinal mucosa of most species contains an abundance of polyamines, these results suggest that, in its free form, spermine may subserve a functional role in the inhibition of gastrointestinal motility.

Animals↗

Passage of the first stool in very low birth weight infants.

Times of first stool passage were studied in 171 infants who weighed less than 1,500 g at birth. Delayed passage (greater than 48 hours) was noted in 20.4% of this group. Significant differences were noted between the delayed and nondelayed groups for gestational age, presence of severe respiratory distress syndrome, and the time of the first enteral feeding. In very low birth weight infants, delay in the passage of the first stool is a common occurrence. This delay is probably due to physiologic immaturity of the motor mechanisms of the gut, lack of triggering effect of enteral feeds on gut hormones, and the presence of severe respiratory distress syndrome, which may singly or in concert adversely affect gastrointestinal motility.

Defecation↗

[Anorexia nervosa or somatic disease].

We have studied 18 patients with anorexia nervosa with antroduodenal manometry for 24 hours and also 24 hours oesophageal pH studies. After the first 12 hours of measurements we started treatment with Cisapride (n = 8) or Erythromycin (n = 10) in a blind study. The results of measurements reveal a severe gastroesophageal reflux in 4 patients. Antroduodenal manometry showed dysfunctions in gastric motility, without relation with weight loss or duration of the disease. Cisapride and more so Erythromycin favor gastrointestinal motility.

Adolescent↗

Vagus-dependent disruption of interdigestive canine motility by gastric distension.

The purpose of this study was to determine the effect of proximal gastric distension on interdigestive patterns of canine gastrointestinal motility and to examine the role of extrinsic nerves in regulating such an effect. Serosal electrodes were placed on the antrum, duodenum, and jejunum. Animals were studied before and after transthoracic vagotomy or after neural isolation of the entire jejunoileum (extrinsic denervation). Proximal gastric distension for 5 h was provided by inflating with air a thin complaint bag placed into the proximal stomach after the onset of phase III of the migrating motor complex (MMC). Four volumes (0, 1.5, 12.5, and 25 ml/kg) were each tested four times in each animal. In neurally intact animals, gastric distension with volumes of 12.5 and 25 ml/kg consistently abolished the MMC in the antrum (100%), duodenum (96%), and proximal jejunum (greater than or equal to 62%), but less often in distal jejunum (greater than or equal to 25%). After vagotomy, gastric distension did not inhibit cycling of the MMC in the antrum, duodenum, or proximal or distal jejunum. After extrinsic denervation of the jejunoileum, gastric distension inhibited the MMC in the antrum and the duodenum but had no effect in the proximal or distal jejunum. These findings suggest that nonnutrient proximal gastric distension may contribute to postprandial changes in patterns of myoelectric activity in the upper gastrointestinal tract and that this effect is mediated by the vagus nerves.

Animals↗

Antroduodenal motility and transpyloric fluid movement in patients with diabetes studied using duplex sonography.

BACKGROUND/AIMS: To elucidate the relationship between diabetic autonomic neuropathy and gastrointestinal motility, antroduodenal motility was studied in patients with diabetes using duplex sonography. METHODS: Antroduodenal motility, transpyloric fluid movement, and velocity curves of fluid flow were studied using duplex sonography in 32 patients with diabetes and 10 healthy subjects after their ingestion of a meat soup. RESULTS: The frequency of antroduodenal coordination was significantly reduced in patients with diabetes with both early and definite autonomic neuropathy compared with healthy subjects (P < 0.05 and P < 0.01, respectively). The frequency and duration of end-cycle reflux episodes were also significantly reduced in patients with early and definite autonomic neuropathy compared with healthy subjects (P < 0.05 and P < 0.01, respectively). The frequency of end-cycle reflux episodes was closely correlated with the frequency of antroduodenal coordination in both healthy subjects (r = 0.859; P = 0.002) and patients with diabetes (r = 0.929; P = 0.0001). There was a significant correlation between fasting plasma glucose concentrations and the frequency of antroduodenal coordination in patients with diabetes (r = -0.361; P = 0.039). CONCLUSIONS: These findings suggest that reduced frequency and duration of end-cycle reflux episodes may be an early indicator of diabetic gastroparesis that may be related mainly to autonomic neuropathy but also in part to acute hyperglycemia.

Adult↗

A novel portable perfused manometric system for recording of small intestinal motility.

The development of solid-state catheters with miniature pressure transducers and portable dataloggers with a large memory capacity has allowed recording of gastrointestinal motility in ambulant subjects. Developments in silicone rubber extrusion technology made it possible to build a perfused manometric system, using a perfused manometric assembly requiring a low volume of perfusate. In the present study the feasibility of recording and automated analysis of small intestinal motility using a perfused multiple lumen manometric system was evaluated in seven healthy volunteers. Pressures were recorded from 12 sideholes arranged in four clusters spaced at 10-cm intervals from the catheter tip. Each channel was perfused at 0.15 mL min-1 with degassed water by a portable, low-compliance, perfusion pump. The 12 sidehole recording channels were connected to external transducers mounted on a belt. Pressure data were stored in two dataloggers. Motility was recorded in the sitting (30 min), and supine (30 min) position, during walking (30 min) and postprandially (90 min). Using purpose-built software baseline variations were corrected for and manometric variables (number of pressure waves, mean amplitude and motility index) calculated. Bench testing of the manometric assembly showed a median baseline pressure offset of 4.2 kPa (range 3.7-10.1) and upon occlusion a rise rate of 27.8 kPa sec-1 (range 19.7-30.8). Changes in body position affected baseline pressures so that compared to the supine position changes in baseline pressure varied between 1.5 +/- 0.7 kPa and 1.9 +/- 0.6 kPa during sitting (P < 0.02), and between 1.7 +/- 0.7 kPa and 1.5 +/- 0.9 kPa during walking (P < 0.03). Manometric recordings obtained during the fasting period showed an increase in small intestinal motor activity during walking. In the postprandial period no differences in motility variables were observed within one cluster and in time. Recording of small intestinal motility with a multiple-channel silicone rubber manometric assembly with a portable perfusion system is a feasible technique which is relatively inexpensive. Computer-assisted data processing allows for adequate elimination of artefacts and automated numerical analysis.

Adult↗

[New method of non invasive examination of the gastroenteric tract].

A new non-invasive method for studying the gastrointestinal tract. The Authors, after a critical evaluation of the methods used to study gastrointestinal motility, evaluate the diagnostic power of electrical activity recorded from the abdominal surface. Physiological principles of gastrointestinal electrical activity, recording methods and statistical analyses of the signal are discussed. A review of the literature is included. It is suggested that this method represents a more accurate, non-invasive diagnostic tool for gastrointestinal disorders.

Electrodiagnosis↗

Otilonium bromide: a selective spasmolytic for the gastrointestinal tract.

Experimental studies have shown that otilonium bromide (OB) inhibits both baseline and chemically or physically stimulated gastrointestinal motility. The spasmolytic activity of OB in the gastrointestinal tract occurs at doses that do not affect gastric secretion or produce typical atropine-like side-effects. The mechanism of action is composite: interference with calcium ion movement from intra- and extracellular sites; blockade of calcium channels; and binding to muscarinic receptors and tachykinin neurokinin-2 receptors. Pharmacokinetic studies have shown that OB accumulates in the lower intestine and has poor systemic absorption. Clinical studies have confirmed OB as a potent spasmolytic drug with a good tolerability profile. Studies in patients with irritable bowel syndrome demonstrated OB to be superior to placebo and reference drugs in parameters such as pain, abdominal distension and motility. The composite and local mechanism of OB action reduces hypermotility and modulates visceral sensation: factors thought to be responsible for pain improvement recorded in clinical trials. The compound is marketed worldwide and no serious adverse events have been reported as yet, confirming its excellent tolerability.

Animals↗

Plasma cholecystokinin, plasma peptide YY and gallbladder motility in patients with slow transit constipation: effect of intestinal stimulation.

BACKGROUND/AIM: Because cholecystokinin and peptide YY are gut hormones with potent effects on gastrointestinal motility, we determined whether abnormalities of cholecystokinin and peptide YY exist in slow transit constipation. METHODS: Plasma concentrations of these hormones before, during and after intraduodenal infusion of a liquid meal in 21 patients with slow transit constipation were compared with the results in 8 healthy controls. RESULTS: Fasting levels of plasma cholecystokinin (3.1+/-0.2 vs. 2.4+/-0.2 pM; p = 0.02) were higher in patients. Basal plasma peptide YY (11.4+/-1.4 vs. 8.9+/-0.7 pM; p = 0.1) tended to be higher in patients. After the meal (60-90 min), incremental cholecystokinin (p<0.05), but not peptide YY, was significantly higher in patients. During intraduodenal infusion of the meal (0-60 min), incremental plasma cholecystokinin (251+/-20 pM.min) and peptide YY (1,146+/-186 pM. min) in patients were almost similar to control values (262+/-22 and 901+/-166 pM. min). Gallbladder volumes before, during and after the meal were not different between the 2 groups. Gastric emptying of a solid meal was delayed in the majority of patients (12 of 18). Abnormalities of plasma cholecystokinin were observed only in patients with delayed gastric emptying. CONCLUSION: Plasma levels of cholecystokinin are elevated in the fasting state and decrease more slowly after stimulation, but maximum release in response to intestinal nutrients is not altered in patients with slow transit constipation. The abnormality seems to be confined to a subgroup of patients with delayed gastric emptying.

Adult↗

Role of serotonin in the pathophysiology of the irritable bowel syndrome.

The irritable bowel syndrome (IBS) is a complex disorder that is associated with altered gastrointestinal motility, secretion, and sensation. Serotonin (5-HT) is an important neurotransmitter and paracrine signalling molecule in the gastrointestinal tract. 5-HT release from enterochromaffin (EC) cells initiates peristaltic, secretory, vasodilatory, vagal and nociceptive reflexes. The enteric nervous system (ENS) comprises a semiautonomous effector system that is connected to the central autonomic network. Parasympathetic and sympathetic nerves modulate the ENS via afferent and efferent communications. Ongoing, bidirectional brain-gut interactions involving 5-HT pathways occur that significantly influence the effector systems. Altered 5-HT signalling may lead to both intestinal and extraintestinal symptoms in IBS. 5-HT directly and indirectly affects intestinal motor and secretory function and abnormalities may lead to either constipation or diarrhea. 5-HT modulates sensation and perception of visceral stimulation at peripheral and central sites. Therapeutic agents targeting altered 5-HT signalling may provide new, effective treatments for patients with IBS.

Animals↗

Effect of erythromycin on gastric and gallbladder emptying and gastrointestinal symptoms in scleroderma patients is maintained medium term.

OBJECTIVES: Scleroderma patients frequently present esophageal and gastric emptying abnormalities and small bowel dysfunction. Erythromycin, a macrolide antibiotic, has been found to accelerate gastric and gallbladder emptying in both healthy subjects and diabetic patients. Our objective was to investigate the effects of 4-wk oral erythromycin administration on the gastric and gallbladder emptying, gastrointestinal symptoms (early satiety, abdominal pain, nausea, bloating, vomiting, and constipation), and motilin plasma levels of patients with scleroderma. METHODS: 12 scleroderma patients were investigated before and after 4-wk treatment with 250 mg oral erythromycin three times a day. The effect of a single i.v. dose of 2 mg/kg/h erythromycin on gastric and gallbladder emptying before starting the oral treatment was also evaluated. Gastric and gallbladder emptying after a solid meal were evaluated by sonography. RESULTS: Single i.v. administration of erythromycin before the meal reduced gastric emptying T1/2 from 121.3 +/- 14.0 to 45.5 +/- 7.3 min (p < 0.01) and accelerated gallbladder emptying without affecting the peak. Four-week oral administration of erythromycin reduced gastric emptying T1/2 from 121.3 +/- 14.0 min to 46.5 +/- 8.3 min (p < 0.01). Peak gallbladder emptying was also significantly accelerated, while total emptying remained unchanged (p < 0.01). Furthermore, 4-wk erythromycin administration reduced both motilin plasma levels (from 223.4 +/- 53.8 to 145.4 +/- 67.2 pmol/L, p < 0.01) and symptoms of nausea, vomiting, and abdominal pain (p < 0.01), and increased bowel movements in a subset of scleroderma patients with intestinal pseudo-obstruction. CONCLUSIONS: Erythromycin stimulates gastrointestinal motility in patients with scleroderma. Administered medium-term, it accelerates gastric and gallbladder emptying and alleviates gastrointestinal symptoms.

Drug Administration Schedule↗

Central control of intestinal motility by prostaglandins: a mediator of the actions of several peptides in rats and dogs.

The effect of intracerebroventricular and intravenous administrations of prostaglandin E2 on gastrointestinal motility were investigated in conscious rats and dogs using electrodes and strain gauges, respectively. Injections were performed during the fed state and the motor changes were compared with those after intracerebroventricular administration of calcitonin, neurotensin, and (D-Ala2, Met5) enkephalinamide. Intracerebroventricular administration of prostaglandin E2 (0.5 micrograms) to fed rats restored the migrating myoelectric complex for 67 +/- 16 min. A migrating myoelectric complex-restoring effect was also observed after intracerebroventricular administration of calcitonin (0.02 U) and neurotensin (80 ng). This effect was blocked by previous intracerebroventricular administration of indomethacin (0.25 mg). Administered centrally to dogs but not intravenously at a 10-fold greater dose, prostaglandin E2 (0.1 microgram/kg) reduced (52.8%) the duration of the jejunal postprandial motor state similarly to that observed after intracerebroventricular administration of calcitonin (0.1 U/kg), neurotensin (0.1 microgram/kg), and (D-Ala2, Met5) enkephalinamide (0.1 microgram/kg). These effects of calcitonin and neurotensin were abolished 4 h after an intramuscular injection of indomethacin (2 mg/kg), whereas those of (D-Ala2, Met5) enkephalinamide persisted. These results suggest that (a) prostaglandins act centrally to control the pattern of intestinal motility in both rats and dogs and (b) calcitonin and neurotensin when injected intracerebroventricularly affect the intestinal motor profile probably by stimulating prostaglandin release within the brain.

Action Potentials↗

[Endogenous ethanol production in patients with liver cirrhosis, motor alteration and bacterial overgrowth].

BACKGROUND: Small intestinal bacterial overgrowth generates endogenous ethanol production both in experimental animals and humans. Patients with cirrhosis have small intestinal bacterial overgrowth, but endogenous ethanol production has not been studied in them. AIM: To investigate endogenous ethanol production in patients with cirrhosis, altered intestinal motility and small intestinal bacterial overgrowth. PATIENTS AND METHODS: Eight patients with cirrhosis of different etiologies and altered gastrointestinal motility, consisting in changes in the migrating motor complex, were studied. All had also small intestinal bacterial overgrowth, measured by means of the H2 breath test with lactulose. Plasma ethanol levels were measured by gas liquid chromatography in fasting conditions and 120 min after a carbohydrate rich meal. RESULTS: In fasting conditions, no patient had endogenous ethanol production. Alter the meal, ethanol in concentrations of 11.3 and 8.2 mg/del were detected in two patients. Negligible amounts of ethanol were detected in 4 patients and two patients had undetectable alcohol levels. CONCLUSIONS: A low endogenous production of ethanol was demonstrated in six of eight patients with cirrhosis.

Adult↗

Antinociceptive and gastrointestinal effects of opiates: an analysis of the nature of the involvement of mu and delta receptors of the central nervous system in morphine-tolerant and non-tolerant mice.

This study attempted to distinguish between mu (morphine) and delta [(D-Ala2-D-Leu5)-enkephalin; DADLE] receptors, with regard to both in vivo effects (analgesia and gastrointestinal motility) and the location of binding activity in the brain. Analgesia and motility are distinguishable both by dose (intracerebroventricular) and by ligand selectivity with mu ligands more potent for the former and delta for the latter. Tolerance and cross-tolerance are exhibited for both effects, with the relationships between mu and delta ligand potencies preserved. In vitro receptor binding revealed an affinity decrease for delta in medulla and an increase in medulla and diencephalon for mu receptors after tolerance development to morphine. The results indicate that the mu receptors in medulla and diencephalon mediate analgesia, while medullary delta receptors control motility.

Analgesia↗

Effects of ageing on gastrointestinal motor function.

BACKGROUND: Existing data on the effect of ageing on gastrointestinal motility are few. In this study, we assessed the propulsive effect of all main segments of the gastrointestinal tract in a group of healthy older people. METHODS: 16 healthy volunteers (eight women, eight men) of mean age 81 years (range 74-85 years) participated in the study. Gastric emptying and small intestinal and colonic transit rates were determined by gamma camera technique. The technique was also used to measure the postprandial frequency of antral contractions. Furthermore, we assessed the effects of gender, body mass index and smoking on the motility variables. The results were compared with data from 16 healthy individuals (eight women, eight men) of mean age 24 years (range 20-30 years). RESULTS: Advanced age did not influence gastric emptying or small intestinal transit rate. Older individuals had a slower colonic transit than young individuals (P = 0.0008). No difference was found in postprandial frequency of antral contractions between older and young subjects. None of the motility variables was affected by gender or body mass index. Smokers had a faster colonic transit than non-smokers (P = 0.0022). CONCLUSION: Normal ageing seems to reduce the propulsive capacity of the colon, whereas gastric and small intestinal motility is not affected.

Adult↗