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[Early diagnosis of diabetic gastroparesis].

Recognition of early phases of diabetic gastroparesis is hampered by the absence of characteristic symptoms and practicable detection systems in clinical practice. Hence, a new procedure estimating phase III activity of the interdigestive migrating motor complex by monitoring gastric emptying of an undigestible marker particle by means of a metal detector was evaluated in 40 diabetic patients (13 type I, 27 type II diabetes) and 14 non-diabetic controls. Simultaneously, orocecal transit of fluids was measured by the hydrogen breath test. Gastric emptying of a solid marker was significantly delayed in diabetics as compared with controls (112.5 +/- 8.6 vs 51.2 +/- 6.8 minutes, M +/- SEM, p < 0.05). Of the diabetics investigated 77.5% had delayed gastric emptying but only 22.5% of those were clinically symptomatic as assessed by a standardized questionnaire. Gastric emptying velocity did not correlate significantly with age, length of diabetes, neuropathy, blood glucose and orocecal transit of fluids. We conclude that determination of gastric emptying time of undigestible marker particles by means of a sensitive metal detector appears to be a clinically promising and easy to perform method to detect early phases of diabetic gastroparesis.

Adult↗

Role of bile in regulation of gut motility.

Bile empties into the duodenum not only after a meal but also in the interdigestive state. In man, interdigestive biliary emptying is related to fasting motor activity, the migrating motor complex (MMC), in the stomach and small bowel and generally occurs during phase 2 preceding a gastroduodenal phase 3 activity (activity front). It seems that the main regulatory peptide to initiate phase 3 is motilin. During a period with 13 phase 3 activities of MMC, 18 episodes of gall-bladder emptying and 19 motilin peaks were observed. Such a peak of plasma motilin usually took place 25 +/- 11 min after onset of biliary emptying. In conclusion, data indicate that motilin is released to the circulation by the biliary output and induces phase 3 of MMC. The induced phase 3 propels bile acids along the gut to promote their absorption in the distal intestine. The choleretic action of recycling of bile acids may cause subsequent episodes of biliary emptying with motilin release by the action of the enterohepatic circulation of bile acids. In such a manner the MMC may be withheld as a recycling motility pattern.

Animals↗

Neural control of the internal anal sphincter motility.

Control mechanism of smooth muscle movement of the internal anal sphincter (IAS) by enteric and extrinsic neuvous systems in the dog was investigated. Responses of IAS muscle strips to electrical field stimulation (EFS) and neurotransmitter agents were recorded in vitro. The contraction response to norepinephrine or to EFS was inhibited by phentolamine. The relaxation induced by EFS was not affected by phentolamine, propranolol or atropine. The mechanical activity of smooth muscle in colon and anorectum during spontaneous defecation was recorded using strain gauge force transducers. The colon and anorectum showed the characteristic motility pattern during defecation: 1) The giant migrating contraction of the colon propagated to the rectum, 2) The relaxation of the rectum prior to the contraction, and 3) The IAS muscles continued to relax while the giant contractions of the colon were migrating to the rectum. Sacral nerves were stimulated electrically and the responses of smooth muscles in the rectum and IAS were recorded. The sacral nerve stimulation induced a relaxation followed by contraction of smooth muscle in the rectum and the relaxation in IAS. The mechanical responses of smooth muscle in the IAS were modulated by alpha-adrenergic excitatory and non-adrenergic, non-cholinergic inhibitory nerves. During defecation, the relaxation of IAS smooth muscle was associated with a characteristic motility pattern of the colon and anorectum. The enteric nervous systems may be organizing the motility of these muscles by way of the motor neurones under the control the extrinsic nervous systems.

Anal Canal↗

Biliary pressure variation in coordination with migrating motor complex of duodenum in patients with cholecystectomy and effects of morphine and cerulein.

Pressures in the common bile duct and duodenum were continuously measured with two pressure microtransducers placed by endoscopy in 10 postcholecystectomy patients. A complete cycle of the migrating motor complex of the duodenum was obtained in seven patients, its length ranging from 62 to 174 min with a mean of 114 min. The biliary pressure showed a transient elevation of 5.0 +/- 0.6 (mean +/- SEM) mm Hg (P < 0.001) in concert with phase III of the duodenal cycle in all 10 patients, whereas it remained stable during other phases. Intramuscular morphine (0.2 mg/kg) given to induce spasm of the sphincter of Oddi 20 min after the passage of phase III invariably produced an activity front in the duodenum and a sustained increase in the biliary pressure, the magnitude of which was 8.3 +/- 0.9 mm Hg. The biliary pressure raised by morphine dropped after an intravenous injection of cerulein (0.1 microgram/kg) as a sphincter relaxant. These findings indicate that the biliary pressure rises transiently at phase III of the duodenal cycle in patients after cholecystectomy, probably due to contractions of the sphincter of Oddi.

Adult↗

Immunocytes and abnormal gastrointestinal motor activity during ileitis in dogs.

Infiltration of specific immunocytes and stimulation of abnormal gastrointestinal motor activity during ileal inflammation induced by mucosal exposure to ethanol and acetic acid were investigated in 17 dogs. Ileal inflammation significantly increased the frequency of giant migrating contractions (GMCs) and decreased the frequency of migrating motor complexes (MMCs). The frequency of retrograde giant contractions (RGCs) increased only on the day of ethanol and acetic acid treatment. Diarrhea, urgency of defecation, and apparent abdominal discomfort were related to the increased frequency of GMCs. Ileal inflammation also prolonged the duration of postprandial MMC disruption. Histological and immunohistochemical findings indicated transmural inflammation with marked increase in polymorphonuclear cells in the lamina propria and muscularis externa layers. Myeloperoxidase activity increased severalfold in both layers. Cells containing interleukin-2 receptor (IL-2R) increased in the lamina propria. Other immunocytes, such as B and T lymphocytes, dendritic cells, and human leukocyte antigen DR-1 (HLADR)-positive cells, did not exhibit a significant increase in the inflamed ileum compared with the normal proximal jejunum. We conclude that stimulation of GMCs may be the major motility marker of intestinal inflammation.

Animals↗

Morphine and gastroduodenal motility.

This study investigated the effects of intravenous morphine on gastric antral and duodenal motility in healthy volunteers. Intravenous morphine (both infusion and bolus) increased duodenal motility, typically as bursts of contractions similar to phase III of the migrating motor complex. Intravenous infusion of morphine 40 microg/kg/hr rapidly increased duodenal motility in nine of 10 subjects; in eight it was phase III-like. Intravenous infusion of naloxone (40 microg/kg/hr) blocked this effect of morphine infusion in five of six subjects. Morphine bolus injection (5-20 microg/kg) in six subjects (30-42 min following a spontaneous phase III) induced further duodenal phase III-like activity; also, morphine bolus injection (5-20 microg/kg) in five subjects (30-42 min following a liquid meal) induced duodenal phase III-like activity. Atropine (10 microg/kg intravenously) was able to prevent the action of morphine (both intravenous infusion and intravenous bolus injection) in inducing this phase III-like activity. These observations show: (1) morphine in very low dose is able to stimulate maximal duodenal contractility; (2) the motility response is typically phase III-like; and (3) morphine acts on opioid receptors to initiate this phase III-like activity, with the effect blocked by antimuscarinic drugs.

Adult↗

Contractile patterns in patients with severe chronic dyspepsia.

OBJECTIVE: Antroduodenojejunal interdigestive and postprandial pressure recordings were analyzed in 41 consecutive patients referred for evaluation of severe chronic dyspepsia. In addition to traditional manometric evaluation we also focused on the propagation pattern of individual pressure waves in the proximal duodenum. METHODS: Catheters with closely spaced side holes for temporospatial analysis of the computerized recordings were used. The dominating symptoms were unexplained nausea and vomiting (n = 18), chronic abdominal pain (n = 16), or both (n = 7). The patients' mean age was 45 yr (31 women and 10 men). Gastric surgery had been performed on 11 patients. Results from 20 healthy volunteers served as a reference range. RESULTS: Findings were suggestive of neuropathy in 16 (39%) and myopathy in 1 (2.4%) using conventional criteria. Another 19 patients of the 24 with normal condensed recordings showed abnormalities in the propagation pattern of individual pressure waves in phase II and/or during the fed state, when compared with the controls. Absence of phase III of the migrating motor complex was found in 12 patients during the 5-h fasting recording, compared with none in the controls (p < 0.01). Retroperistalsis at the end of phase III in the duodenum was present in at least one of the activity fronts in all patients having migrating motor complex except one, which was similar to the controls. During phase II, unpropagated bursts of phasic and tonic activity were more frequent in patients than in controls (mean 13.2% vs 3.7% of the time; p < 0.05), and a higher proportion of individual contractions was retrograde in patients than in controls (17.4% vs 5% of propagated contractions; p < 0.05). Patients had higher postprandial motility index in the distal duodenum than did controls (p < 0.05). Moreover, after feeding more individual contractions were retrograde in patients than in controls (33.1% vs 10% of propagated contractions; p < 0.01). Sequences of localized supratachyarrythmia, 25-35/min in the antrum and 50-60/min in the small bowel associated with symptoms, were observed in two patients. CONCLUSION: Manometry is important for demonstration of pathophysiology in patients with unexplained abdominal pain, nausea, and vomiting. Simultaneous analysis of the propagation of individual contractions of interdigestive and fed motility is superior to conventional manometry alone.

Adolescent↗

Tachykinins potently stimulate human small bowel blood flow: a laser Doppler flowmetry study in humans.

BACKGROUND: The two tachykinins substance P and neurokinin A are abundantly present in the gastrointestinal tract. Substance P preferring neurokinin 1 receptors are mainly found in submucosal blood vessels while neurokinin A preferring neurokinin 2 receptors seem to be confined to smooth muscle cells. Tachykinin effects on intestinal mucosal blood flow in humans are not known. AIM: To study the effects of substance P and neurokinin A on small bowel mucosal blood flow in humans. METHODS: A manometry tube supplied with single fibre microprobes recorded mucosal blood flow in the proximal small bowel using laser Doppler flowmetry, concomitant with luminal manometry, defining phases I, II, and III of the migrating motor complex. Simultaneously, flowmetry of temporal skin was performed. Under fasting conditions saline was infused intravenously over four hours followed by infusion of substance P, neurokinin A, or saline. RESULTS: During phase I, substance 1-6 pmol/kg/min increased mucosal blood flow dose dependently by a maximum of 158%. Blood flow of the temporal skin increased in parallel. Neurokinin A 6-50 pmol/kg/min increased mucosal blood flow maximally by 86% at 25 pmol/kg/min while blood flow of temporal skin increased at all doses. Substance P at all doses and neurokinin A at the highest dose only, increased pulse rate. Systolic blood pressure was unchanged by either peptide while substance P at the highest dose decreased diastolic pressure. CONCLUSION: Tachykinins increase blood flow of the small bowel and temporal skin. With substance P being more potent than neurokinin A, these effects are probably mediated through neurokinin 1 receptors.

Adolescent↗

Effect of dopamine on gastrointestinal motility during critical illness.

OBJECTIVE: To document the action of dopamine on gastrointestinal motility in mechanically ventilated patients. DESIGN: Crossover, randomized, placebo-controlled study. SETTING: General intensive care unit (ICU) in a university hospital. PATIENTS: Twelve mechanically ventilated patients in a stable hemodynamic condition, with no contraindication to enteral feeding. INTERVENTIONS: Dopamine (4 microg/kg per minute) and placebo were infused over 8 h (4 h fasting, followed immediately by 4 h nasogastric feeding at 100 kcal per hour) on two consecutive days, in a random order. Pressure changes in the gastric antrum (four sites) and in the duodenum (two sites) were recorded by perfused catheter manometry. Each session started with the institution of dopamine or placebo infusion. MEASUREMENTS AND RESULTS: The migrating motor complex and its three successive phases were identified (phase I, period of quiescence; phase II, period of irregular contractile activity; phase III or activity front, period of high-frequency, regular contractions). Contractions and activity fronts at each site were quantified during fasting and feeding. The mean duration of the fasting migrating motor complex was determined in the duodenum, as well as the contribution of each phase (phases I, II, III) to the length of the complete cycle. The propagation characteristics of each activity front were assessed visually. The number of contractions was lower in the antrum (p = 0.024) and phase III motor activity higher in the duodenum [incidence of activity fronts (p = 0.008); number of phase III contractions (p = 0.009)] during dopamine infusion than with placebo. These modifications observed under dopamine were related to decreased antral contractions during fasting (p = 0.050), increased incidence of activity fronts during feeding (p = 0.031), and increased number of phase III contractions during fasting (p = 0.037). In both groups (placebo and dopamine) activity fronts rarely started in the antrum, and abnormally propagated activity fronts were found in the duodenum in some patients. CONCLUSIONS: Low-dose dopamine adversely affects gastroduodenal motility in mechanically ventilated critically ill patients.

Adult↗

Gastric output of IgA in man: relation to migrating motility complexes and sham feeding.

BACKGROUND/AIMS: The immunologic reactivity of the gastric mucosa is poorly understood. The origin and dynamics of immunoglobulin A (IgA) occurring in the gastric lumen were investigated in healthy, Helicobacter pylori-negative volunteers. METHODS: Gastroduodenal manometric motility recordings were combined with gastric luminal perfusion, enabling calculation of gastric acid output and analysis of the total IgA output. RESULTS: Acid output and total IgA correlated with the migrating motility complexes (MMC). The gastric IgA release showed maximal values in association with gastric motility phase III (maximal motor activity) and lowest values during phases I and II (none or irregular motor activity). The IgA output correlated with neither swallowed saliva (as indicated by amylase in the gastric perfusate) nor duodenogastric reflux (as indicated by gastric occurrence of bilirubin and/or duodenally infused PEG4000). Stimulation of gastric acid secretion by sham feeding during phase II-like motor activity (n = 6) induced a rapid and transient doubling of IgA output. There was no significant correlation between gastric acid secretion and gastric IgA release. CONCLUSION: Substantial amounts of IgA are released into the human stomach, most likely originating from the gastric mucosa. The up-regulation of IgA release in association with the activity front of the MMC and anticipatory to food intake suggests a neuroendocrine control of gastric mucosal immune responses.

Adult↗

Effect of a tricyclic antidepressant on small intestinal motility in health and diarrhea-predominant irritable bowel syndrome.

Antidepressants are used in irritable bowel syndrome (IBS) and may have effects on the gut independent of improving mood. We have investigated the actions of a tricyclic antidepressant on small intestinal motor function in eight healthy volunteers and in six patients with diarrhea-predominant IBS. Fasting ambulatory motility was recorded from six small intestinal sites for 16-18 hr while on no drug (baseline) and while taking imipramine for five days. Orocecal transit time (OCTT) was measured by lactulose hydrogen breath test, during baseline and imipramine administration. Imipramine did not alter migrating motor complex periodicity, but slowed jejunal phase III propagation velocity in controls from 7.5 +/- 1.1 to 3.6 +/- 0.5 cm/min (P < 0.01) and in IBS from 7.8 +/- 0.6 to 4.4 +/- 0.5 cm/min (P < 0.0001). Phase III duration at each site was increased, and total recorded phase III was greater during imipramine than baseline studies. Imipramine increased the amplitude of phase III contractions. There was no effect of imipramine on non-phase-III motility index or discrete clustered contractions. Imipramine, prolonged OCTT from 73 +/- 6 min to 97 +/- 8 min in controls (P < 0.05) and from 61 +/- 9 min to 89 +/- 8 min in IBS (P < 0.05). Although OCTT was shorter in the IBS group, no motility differences were seen between controls and IBS. This demonstration that a tricylic antidepressant can modify small intestinal motor function in health and in IBS supports the view that these drugs may have therapeutic actions in IBS unrelated to mood improvement.

Adult↗

The influence of induced hyperglycaemia on the characteristics of intestinal motility and bile kinetics in healthy men.

Simultaneous recording of duodenal motility and biliary scintigraphy by continuous infusion of 99mTc-dimethyl-iminodiacetic acid was performed in 16 healthy fasted men, of whom eight had an intravenous glucose bolus injection immediately after the passage of a duodenal phase III of the migrating motor complex (MMC). This was followed by a continuous intravenous infusion of glucose. Characteristics of the time-activity curves from the gallbladder area and intestinal area were related to phase activity of the duodenal MMC. The median duration of the entire MMC cycle was significantly shorter in the glucose group than in the group without glucose. The difference was caused by shortening of phase II. Spontaneous gallbladder emptying appeared in all eight subjects from the group without glucose but in only a single subject from the glucose group. The relative amount of liver bile diverted to the gallbladder in the entire cycle was significantly higher in the subjects who received glucose, and in four subjects all the hepatic bile was diverted to the gallbladder. The results demonstrate that induced hyperglycaemia exerts a pronounced effect on gastrointestinal motility and bile kinetics. Available evidence suggests that the effects are caused by a 'medical vagotomy'.

Adult↗

Helicobacter pylori-associated gastritis and dyspepsia. The influence on migrating motor complexes.

Twenty-five patients with dyspepsia were included. In 19 patients with a median age of 48 (range, 20-72) years endoscopy and histologic examination of biopsy specimens from the antrum and corpus of the stomach showed Helicobacter pylori-positive gastritis as the only pathologic finding. In six patients with a median age of 42 (range, 32-56) years H. pylori-negative gastritis was found. After an overnight fast the patients underwent an ambulatory duodenal motility study for 6-8 h. Twenty-five young healthy men served as the control group. In patients with H. pylori-positive gastritis the duration of phase I of the migrating motor complex (MMC) was significantly shorter than in the control group. The median value was 33 min (quartiles, 24-49), and in controls 56 min (40-136 min). Phase II was of significantly longer duration, with a median value of 88 min (51-121 min) in the patient group and 39 min (22-89 min) in the control group. The duration of phase III and the whole MMC cycle was similar in the two groups. However, in the patients with H. pylori-negative gastritis the values of the duration of the different phases of the MMC were similar to those of the patients with H. pylori-positive gastritis. Nine patients were reexamined after eradication of the H. pylori infection, and the motility pattern had changed to the characteristics found in normals. In conclusion, the patients with dyspepsia and gastritis showed a disturbed motility pattern. The disturbance was similar whether there was colonization of H. pylori or not.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Murine intestinal migrating motor complexes: longitudinal components.

Spontaneous migrating contractions have been described in the circular muscle of the isolated mouse colon and terminal ileum, however, spontaneous events equivalent to these have not been reported in the longitudinal muscle. The longitudinal muscle shortenings in the colon and ileum, which are of similar form, frequency and pharmacology to the circular muscle colonic and ileal migrating motor complexes (CMMCs and IMMCs), are recorded in the present study. The spontaneous ileal and colonic longitudinal muscle shortenings appear to be neurally organized as they are abolished by tetrodotoxin (1 micro mol L-1), hexamethonium (500 micro mol L-1) and morphine (1 micro mol L-1). Endogenously released nitric oxide slowed the frequency of spontaneous ileal and colonic longitudinal muscle shortenings and 5-hydroxytryptamine increased their frequency. Hyoscine (1 micro mol L-1) abolished longitudinal shortenings in the ileum and reduced the amplitude of longitudinal shortening by approximately 44% in the colon. Shortenings were effectively abolished by nifedipine (1 micro mol L-1). Surgical sectioning of the colon identified that each region of the colon contracted longitudinally in an independent fashion; the distal colon contracted to the greatest amplitude and lowest frequency. The longitudinal preparation is suitable to initially assess the actions of novel pharmacological agents on spontaneous, neurally coordinated, CMMCs and IMMCs in emptied isolated murine intestines.

Anesthetics, Local↗

Effect of gastrin on antroduodenal motility: role of intraluminal acidity.

The effect of gastrin on the migrating motility complex (MMC) was studied in seven healthy subjects. It was hypothesized that a potential effect of gastrin on the MMC may result from intraluminal acidification through increased gastric acid secretion. Therefore, antroduodenal manometry and intraluminal acidity were recorded simultaneously. The effect of gastric acid inhibition, with and without administration of gastrin, on antroduodenal motility and intraluminal acidity was also evaluated and compared with saline infusion (control). Continuous infusion of gastrin-17 (20 pmol. kg-1. h-1) increased intragastric and intraduodenal acidity and suppressed phase II and phase III motor activity in both antrum and duodenum. Concomitant gastric acid inhibition with intravenous famotidine, as demonstrated by intragastric neutralization of pH, completely antagonized the effect of gastrin on the MMC. In fact, famotidine infusion, both with and without administration of gastrin, significantly shortened MMC cycle length. It is concluded that the effect of gastrin on interdigestive antroduodenal motility results from increased intraluminal acidity.

Adolescent↗

[Effect of electrical lesion of the area postrema on gastrointestinal interdigestive migrating motor complex in conscious dogs].

OBJECTIVE: To investigate the effect of area postrema (AP) of medulla oblongata on gastrointestinal interdigestive migrating motor complex (MMC). METHODS: Interdigestive MMC activity of antrum and duodenum was recorded by strain gauge implanted on the serosa in 8 conscious dogs. Cannula was intubated in the femoral vein for motilin injection. Plasma motilin concentration was measured by RIA. We observed (1) normal interdigestive MMC activity and fluctuation of plasma motilin concentration; (2) the effect of electrically destroying AP on MMC activity and plasma motilin level and (3) whether or not intravenous injection of motilin could induce phase III contractions after AP was destroyed. RESULTS: (1) Typical interdigestive MMC with phases I, II, III and IV was recorded in normal dogs. Phase III was concurrent with the peak of plasma motilin level. (2) In dogs electrically destroyed AP with antroduodenal interdigestive MMC contractions were suppressed; cyclic, phasic and migratory pattern of MMC was disrupted. Plasma motilin concentration was decreased. Intravenous injection of motilin could not induce phase III contractions. CONCLUSION: Area postrema plays an important role, which is mediated by motilin, on the regulation of interdigestive MMC.

Animals↗

Quantitative assessment of motility-associated changes in gastric and duodenal luminal pH in humans.

BACKGROUND: Interdigestive pain relieved by food is a common feature of ulcer disease. We tested the hypothesis that the duodenal bulb is intermittently acidified in association with phase III of the interdigestive motility cycle, and tried to quantify the balance between acid and duodenal bicarbonate secretion during this particular period. METHODS: The experiments were performed in Helicobacter-negative healthy volunteers. Gastric and duodenal luminal pH was measured with a triple antimon electrode before, during, and after phase III of the migrating motor complex. Gastric acid secretion rate was measured in real time with a perfusion system and duodenal bicarbonate secretion was estimated from a continuous recording of the transmucosal potential difference (PD) in the duodenal bulb. RESULTS: No significant changes in bulb pH occurred before, during, or after phase III. During the studied time window, the stomach produced 2.24 +/- 0.55 mmol of acid at a peak pH of 1.74 +/- 0.10. Basal HCO3- secretion calculated from bulb PD was 0.82 +/- 0.12 mmol x 30 min(-1) to which was added 0.47 +/- 0.07 mmol of HCO3- during duodenal phase III. The contribution of retroperistalsis-driven HCO3- reflux was small (0.08 +/- 0.02 mmol). CONCLUSIONS: Both the pH recording and the quantitative assessment of secretion rates show that in healthy subjects, fasting gastric acid production and duodenal bicarbonate secretion are of similar magnitude and dynamically coordinated. The mechanism behind the linkage may be reflex activation by motor activity, or a luminal PCO2 rise during phase III activity.

Adult↗

Biliary motility. Changes in detailed characteristics correlated to duodenal migrating motor complex and effects of morphine and motilin in dogs.

The temporal relationship of biliary motility to the duodenal migrating motor complex and effects of morphine and motilin were studied in five dogs prepared with a duodenal cannula. Common bile duct, sphincter of Oddi, and duodenal manometry were performed awake. Sphincter of Oddi phasic contractions occurred even during the quiescent period of duodenal phase I and its activity increased from phase II to III. Minimum basal pressure of sphincter of Oddi and common bile duct pressure decreased from phase I to phase III. Both morphine and motilin induced premature phase III in the sphincter of Oddi and duodenum. Latencies of the effect were 0.2 min for morphine and 3.2 min for motilin (P < 0.01). After morphine, vigorous continuous contractions with high basal pressure occurred, being interrupted by brief and repeated inactive periods, similar to spontaneous phase III. Motilin-induced phase III appeared indistinguishable from spontaneous phase III. Although both agents induced phase III in the sphincter of Oddi, differences in the latency and contraction pattern suggest different mechanisms of action of these agents on the sphincter of Oddi.

Animals↗