Effect of tolterodine on gastrointestinal transit and bowel habits in healthy subjects

Abstract  Clinical trials and observations suggest that constipation is an uncommon side effect of treating overactive bladder with the muscarinic receptor antagonist tolterodine. Because muscarinic antagonism inhibits gastrointestinal motor activity, we evaluated the effects of tolterodine on bowel habits, gastrointestinal and colonic transit in healthy subjects. In this double-blind study, 36 healthy subjects were randomized to tolterodine extended release (ER, 4 mg daily) or placebo for 6 days. Gastric emptying (GE), small bowel and colonic transit were assessed on days 4–6 by scintigraphy. Bowel habits were recorded by diaries. Tolterodine did not significantly affect half-time for GE (GE t _half) [116 ± 6 min (mean ± SEM) for placebo vs 126 ± 7 min for tolterodine], small bowel transit measured by colonic filling at 6 h (45 ± 6% for placebo vs 36 ± 6% for tolterodine) or the geometric center of colonic transit at 24 h (2.9 ± 0.2 for placebo vs 2.6 ± 0.3 for tolterodine). Subjects who received tolterodine had slightly fewer bowel movements (i.e. 1.34 ± 0.1 stools per day for placebo vs 1.0 ± 0.1 for tolterodine; P  = 0.02 for treatment effect). Tolterodine did not significantly affect stool consistency or ease of defecation. At the therapeutic dose used to treat overactive bladder, tolterodine did not significantly affect gastrointestinal or colonic transit and had minor effects on bowel habits in healthy subjects. Further studies are necessary to elucidate whether these observations are explained by tolterodine effects at muscarinic receptors which stimulate and inhibit gastrointestinal motility.     

Electrical colonic stimulation reduces mean transit time in a porcine model

Abstract  Electrical stimulation is a new way to treat digestive disorders such as constipation. Colonic propulsive activity can be triggered by battery operated devices. This study aimed to demonstrate the effect of direct electrical colonic stimulation on mean transit time in a chronic porcine model. The impact of stimulation and implanted material on the colonic wall was also assessed. Three pairs of electrodes were implanted into the caecal wall of 12 anaesthetized pigs. Reference colonic transit time was determined by radiopaque markers for each pig before implantation. It was repeated 4 weeks after implantation with sham stimulation and 5 weeks after implantation with electrical stimulation. Aboral sequential trains of 1-ms pulse width (10 V; 120 Hz) were applied twice daily for 6 days, using an external battery operated stimulator. For each course of markers, a mean value was computed from transit times obtained from individual pig. Microscopic examination of the caecum was routinely performed after animal sacrifice. A reduction of mean transit time was observed after electrical stimulation (19 ± 13 h; mean ± SD) when compared to reference (34 ± 7 h; P  = 0.045) and mean transit time after sham stimulation (36 ± 9 h; P  = 0.035). Histological examination revealed minimal chronic inflammation around the electrodes. Colonic transit time measured in a chronic porcine model is reduced by direct sequential electrical stimulation. Minimal tissue lesion is elicited by stimulation or implanted material. Electrical colonic stimulation could be a promising approach to treat specific disorders of the large bowel.     

Colonic transit time and anorectal manometric anomalies in 19 patients with complete transection of the spinal cord

In order to determine the relative importance of sympathetic and parasympathetic centers in the control of colorectal motility, colonic transit and anorectal motility were studied in 19 patients with complete spinal cord transection: group 1 (n = 5) where transection was above T9; group 2 (n = 6) where transection was between T9 and L2; group 3 (n = 8) where transection involved S2-S4. Colonic transit time was calculated by the radiopaque markers. Methods and results were compared with those of eight controls, all bedridden for non-digestive surgery. Anorectal motility was investigated by anorectal manometry, and results were compared with those of 17 healthy controls. Both mean right and left colonic transit times were not different in the three groups of patients and the bedridden control group. Mean rectosigmoid and total transit time increased in groups 2 and 3. In five patients of group 3 the mean anal canal (lower part) pressure was higher than in controls. Recto-anal inhibitory reflex was present in all patients, but their was no correlation in group 3 between the volume of rectal distension and both amplitude and duration of the recto-anal inhibitory reflex, and in group 1 between rectal distension and the duration of the recto-anal inhibitory reflex. Rectosigmoid transit time increased when sympathetic and parasympathetic spinal centers are injured, suggesting the importance of this extrinsic nervous control; right and left colonic transit are not affected by spinal cord lesion suggesting that the distal colon but not the proximal colon, is under spinal cord nervous control.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship of cytochrome P450 pharmacogenetics to the effects of yohimbine on gastrointestinal transit and catecholamines in healthy subjects

Abstract  Alpha-2 adrenergic receptors tonically inhibit colonic motility and the α₂-adrenergic antagonist yohimbine, given intravenously, increased colonic tone in humans. However, the effect of yohimbine on colonic transit in humans is unknown. In this study, 30 healthy volunteers were randomized to yohimbine 16.2 mg p.o. t.i.d. or identical placebo for 7 days. We evaluated gastric emptying, small intestinal, and colonic transit by scinitigraphy, bowel habits, haemodynamics and plasma catecholamines. As cytochrome P450 enzymes metabolize yohimbine, P450 genotypes ( CYP2D6 and CYP3A4 ) were determined in 25 of 30 subjects who consented to genetic studies. The relationship between drug metabolizer status predicted by CYP2D6 and CYP3A4 and effects of yohmibine were assessed. Compared to placebo, yohimbine increased ( P  ≤ 0.02) diastolic blood pressure, plasma noradrenaline concentrations and maximum tolerated volume during the satiation test [yohimbine (1241 ± 88, mean ± SEM) vs placebo (1015 ± 87), P  = 0.054]. However, yohimbine did not affect gastrointestinal transit. Based on CYP2D6 and CYP3A4 alleles, seven and 18 subjects were, respectively, extensive (EM) and poor (PM) metabolizers of yohimbine. Compared to EM, PM of yohimbine had a greater increase in plasma noradrenaline ( P  = 0.1 for PM vs EM), lower maximum tolerated volumes (1120 ± 95 vs 1484 + 131 mL, P  = 0.02), and faster colonic transit (i.e. GC₂₄ was 3.0 ± 0.4 vs 2.1 ± 0.5, P  = 0.1). These data suggest that CYP2D6 and CYP3A4 genotypes which determine the metabolism of yohimbine may influence its sympathetic and gastrointestinal effects.     

Effect of transdermal application of nicotine on colonic transit in healthy nonsmoking volunteers

The radio-opaque marker technique (ROMT) is a safe and noninvasive method to determine total colonic (TCTT) and segmental colonic transit times (SCTT). Previous results have shown that smoking volunteers had significantly longer TCTT than nonsmokers, but the underlying mechanism was not clear. We investigated the effect of transdermal nicotine application in two different doses in a nonblind randomized experiment involving three distinct phases. In phase 1 baseline transit times were determined with an abdominal X-ray after a 6-day period of marker ingestion and again after the following bowel movement to study the influence of a bowel movement just before the X-ray. TCTT was nearly twice as high before than after defaecation (42.6 h vs. 25.1 h, P < 0.05). The main acceleration was found in the rectosigmoid (RS) (18.6 h vs 7.1 h, P < 0.05) with no significant changes in right (RC) and left colon (LC). In phase 2 and 3 nicotine was applied in two doses of 17.5 mg day⁻¹ and 35 mg day⁻¹ in random order. Both doses resulted in a significant decrease of TCTT compared to the predefaecation baseline (42.6 h vs 32.2 h/28.2 h, respectively, P < 0.05). Again the main effect was located in the RS (18.6 h vs 9.9 h/7.6 h, P < 0.05). Short-term application nicotine results in a decrease of TCTT which is due to an accelerated transit in the RS.     

Clinical correlates of dysphagia to oesophageal dysmotility: studies using combined manometry and impedance

Abstract  This study aimed to elucidate the mechanism of dysphagia by determining the simultaneous relationships between subjective perception of swallow with oesophageal motility and bolus transport in patients with non-obstructive dysphagia (NOD). Combined oesophageal manometry and impedance was performed in 18 consecutive NOD patients and 14 healthy controls. Swallow was abnormal if the amplitude of distal oesophageal contractions was less than 30 mmHg or simultaneous contractions occurred. Bolus transit was abnormal if bolus exit was not found at one or more of the measuring sites. Perception of each swallow was assessed using a standardized scoring system and was enhanced if score was >1. The prevalence of complete bolus transit was lower in NOD patients compared with healthy controls ( P  = 0.001). Abnormal liquid bolus transit was found in 40% of patients with normal motility and 38% of patients with abnormal motility, whereas abnormal viscous bolus transit was observed in 38% of patients with normal motility and 70% of patients with abnormal motility. Agreement between enhanced perception and impedance was poor during liquid (κ = 0.12, 95% CI: −0.003 to 0.233) and viscous swallowing (κ = 0.12, 95% CI: −0.004 to 0.244). Agreement between enhanced perception and manometry was even poorer during liquid (κ = −0.16, 95% CI: −0.302 to 0.022) and viscous swallowing (κ = −0.12, 95% CI: −0.25 to 0.002). NOD patients show poor correlation between dysphagia and oesophageal motility parameters. The results suggest that, in patients with NOD, oesophageal motor dysfunction may play a limited role, if any, in the generation of dysphagia.     

Colonic movements in healthy subjects as monitored by a Magnet Tracking System

Abstract  The Magnet Tracking System (MTS) is a minimally-invasive technique of continuous evaluation of gastrointestinal motility. In this study, MTS was used to analyse colonic propulsive dynamics and compare the transit of a magnetic pill with that of standard radio-opaque markers. MTS monitors the progress in real time of a magnetic pill through the gut. Ten men and 10 women with regular daily bowel movements swallowed this pill and 10 radio-opaque markers at 8 pm. Five hours of recordings were conducted during 2 following mornings. Origin, direction, amplitude and velocity of movements were analysed relative to space–time plots of the pill trajectory. Abdominal radiographs were taken to compare the progress of both pill and markers. The magnetic pill lay idle for 90% of its sojourn in the colon; its total retrograde displacement accounted for only 20% of its overall movement. Analysis of these movements showed a bimodal distribution of velocities: around 1.5 and 50 cm min^–1, the latter being responsible for 2/3 of distance traversed. There were more movements overall and more mass movements in males. Net hourly forward progress was greater in the left than right colon, and greater in males. The position of the magnetic pill correlated well with the advancement of markers. MTS showed patterns and propulsion dynamics of colonic segments with as yet unmet precision. Detailed analysis of slow and fast patterns of colonic progress makes it possible to specify the motility of colonic segments, and any variability in gender. Such analysis opens up promising avenues in studies of motility disorders.     

Ambulatory long-term jejunal manometry in diabetic patients with cardiac autonomic neuropathy

Concerning alteration of small bowel motility in diabetic patients with autonomic neuropathy controversial data were obtained with stationary manometry and over a limited period of time. The aim of our study was to examine ambulatory 24 h jejunal motility in 15 diabetic patients with cardiac autonomic neuropathy compared with data obtained in 50 healthy controls. Twenty-four hour motility was recorded in the proximal jejunum with a portable datalogger and tube-mounted miniature pressure sensors. Diurnal and nocturnal fasting motility and the motor response to a standardized evening meal of 600 kcal were evaluated by visual and computer-aided analysis. The following abnormalities were found during fasting motility (n = number of patients): absence of phase III over 24 h (n = 2), retrograde migration or simultaneous occurrence of phase III (n = 5). During postprandial motility irregular bursts with tonic baseline elevation (n = 3) and contraction frequencies below the range of controls (n = 8) occurred. Furthermore patients exhibited an inversion of the normal relationship between phase I and phase II during nocturnal MMC – cycles, and discrete clustered contractions were diminished (P < 0.01) in the fasting and digestive state. All patients showed at least one abnormal manometric finding. We conclude that small bowel motility in diabetic autonomic neuropathy is characterized by disturbances in the generation and aboral migration of phase III, an altered circadian variability of the MMC cycle and by postprandial hypomotility.     

Rectal motility after sacral nerve stimulation for faecal incontinence

Abstract  Sacral nerve stimulation (SNS) is effective against faecal incontinence, but the mode of action is obscure. The aim of this study was to describe the effects of SNS on fasting and postprandial rectal motility. Sixteen patients, 14 women age 33–73 (mean 58), with faecal incontinence of various aetiologies were examined. Before and during SNS, rectal cross-sectional area (CSA) and ano-rectal pressures were determined with impedance planimetry and manometry for 1 h during fast and 1 h postprandially. Neither in the fasting state nor postprandially did SNS affect the number of single rectal contractions, total time with cyclic rectal contractions, the number of aborally and orally propagating contractions, the number of anal sampling reflexes or rectal wall tension during contractions. Postprandial changes in rectal tone were significantly reduced during SNS ( P  < 0.02). Before SNS, median rectal CSA was 2999 mm² (range: 1481–3822) during fast and 2697 mm² (range: 1227–3310) postprandially ( P  < 0.01). During SNS, median rectal CSA was 2990 mm² (1823–3678) during fast and 2547 mm² (1831–3468) postprandially ( P  = 0.22). SNS for faecal incontinence does not affect phasic rectal motility but it impairs postprandial changes in rectal tone.     

Effects of an Intestinal Smooth Muscle Calcium Channel Blocker (Pinaverium Bromide) on Colonie Transit Time in Humans

Pinaverium bromide, a calcium channel blocker, is often used in the treatment of the irritable bowel syndrome. Colonie transit time (CTT) was evaluated by a simplified method using radiopaque markers in 19 healthy volunteers during 2 weeks of treatment with pinaverium bromide (50 mg three times a day) or placebo according to a double-blind crossover design. Pinaverium bromide significantly (p < .05) accelerated total CTT (30.2 ± 4.6 h, mean ± SE) compared with the placebo (38.2 ± 3.7 h). The decrease in CTT was related to accelerated transit in the descending and rectosigmoid areas of the colon (21 ± 4.5 vs. 30 ± 3.9 h, p < .05). CTT in the ascending colon was not significantly modified (9.2 ± 2.7 as compared with 9.5 ± 2.3 h). Stool frequency was not significantly increased by pinaverium bromide. These results suggest that pinaverium bromide might be effective in idiopathic constipation with slow CTT in the descending or rectosigmoid areas of the large bowel. The measurement of CTT is an easy and useful method for investigating the effects of drugs on colonie motility.     

Therapeutic effects of loxiglumide, a cholecystokinin antagonist, on chronic constipation in elderly patients: a prospective, randomized, double-blind, controlled trial

Severe chronic constipation is a common health problem, particularly among elderly nursing-home patients. Cholecystokinin (CCK) is involved in the regulation of colonic motility, and the blockade of CCK_A receptors with loxiglumide, a potent and highly specific CCK_A antagonist, dramatically accelerates colonic transit time in healthy human volunteers. The effect of loxiglumide on the bowel habits and colonic transit time in 21 chronically constipated nursing-home patients (mean age 83, range 71–89 years) was studied in a randomized, placebo-controlled, double-blind cross-over study. Loxiglumide 800 mg t.i.d. or identical-looking placebo tablets were given orally in sequence with a 7-day washout period in between for 21 days each. The number of spontaneous bowel movements and that of administered enemas was recorded for each 3-week phase. At the end of each treatment period colonic transit time was assessed using radio-opaque markers. Treatment with loxiglumide significantly (P < 0.005) accelerated colonic transit time from 113 ± 6 to 81 ± 10 h. The frequency of weekly bowel movements increased from 3.9 ± 0.5 (placebo) to 4.9 ± 0.5 (loxiglumide) (P < 0.006), while the number of enemas over the 3 weeks decreased from 2.7 ± 0.6 to 1.3 ± 0.4 for placebo and loxiglumide, respectively (P < 0.005). No serious side-effects were observed and there were no signs of exocrine pancreatic insufficiency induced by loxiglumide. The blockade of CCK_A receptors with loxiglumide significantly improves chronic constipation in geriatric patients. Loxiglumide may therefore constitute the prototype of a new class of potent therapeutic agents effective in the treatment of constipation.     

Effects of Velusetrag (TD-5108) on gastrointestinal transit and bowel function in health and pharmacokinetics in health and constipation

Abstract  Velusetrag (TD-5108) is a potent, selective high intrinsic activity serotonin 5-HT₄ receptor agonist. We assessed effects of Velusetrag on gastrointestinal transit and compared its pharmacokinetics in healthy volunteers (HV) and chronic constipation (CC) patients. Sixty HV were randomly assigned, double-blind to placebo, 5, 15, 30 or 50 mg Velusetrag (single and 6-day dosing). Primary endpoints were colonic transit (geometric centre at 24 h, GC24) and ascending colon emptying (ACE) T _1/2 after first dose. Secondary endpoints included gastric emptying (GE) T _1/2 and colonic filling at 6 h (CF6). Single dose Velusetrag significantly accelerated GC24, ACE T _1/2, and CF6; 30 and 50 mg Velusetrag accelerated all three endpoints. With multiple doses, Velusetrag 30 mg accelerated GC24, and overall accelerated GE T _1/2 at 15–50 mg. Pharmacokinetics studies showed dose proportionality in health, and no significant differences between health and chronic constipation with a 15 mg oral dose of Velusetrag. Stimulation of bowel function after15 mg Velusetrag was similar in CC and controls. There were no serious adverse events; notable adverse events were the predictable gastrointestinal effects such as diarrhoea or altered bowel movements. Velusetrag significantly accelerated intestinal and colonic transit after single dosing and accelerated gastric emptying after multiple dosing. Further studies of its potential as a gastrointestinal and colonic prokinetic are warranted.     

20Electrogastrography is of limited value in the diagnosis of motility disorders

Background:  Electrogastrography (EGG) is a technique for recording gastric myoelectric activity. Conflicting results were obtained in previous studies when EGG was applied in motility disorders of the stomach associated with various systemic diseases.
Aim:  To investigate whether the underlying diagnosis could be predicted from EGG parameters.
Material and methods:  This is a retrospective analysis of patients with motility disorders who underwent EGG as part of their clinical work-up. A single bipolar channel measured the EGG. The ability of EGG to identify diagnostic groups was tested by comparing 21 EGG parameters for each diagnostic group or symptom against all other patients in the sample.
Results:  A total of 151 patients, 125 (83%) females, and mean age 45 ± 14 years were analysed. There were 52 patients with irritable bowel syndrome (IBS), 22 with enteric dysmotility, 26 with slow transit constipation (STC), 11 with chronic intestinal pseudo-obstruction (CIP), 13 with gastroparesis or functional dyspepsia, three post-surgical, and 24 patients with other diagnoses. In general, the discriminatory power of EGG for underlying motility disorder was low. Only those with STC showed a reasonable number of differences in EGG parameters compared to all other groups (Table). Patients with IBS had lower fasting and postprandial variability of the dominant frequency (DF) and a higher percentage of postprandial time with normogastric DF.
Conclusion:  The ability of EGG to identify motility disorders as well as symptoms in general was poor. EGG findings in patients with STC require validation.
 

     

14.

Vagal activation by sham feeding improves gastric motility in functional dyspepsia   总被引：1，自引：0，他引：1  

j. a.  lunding  †  l. m.  nordström  a.-o.  haukelid  o. h.  gilja  †  a.  berstad  & t.  hausken  † 《Neurogastroenterology and motility》2008,20(6):618-624

Abstract  Antral hypomotility and impaired gastric accommodation in patients with functional dyspepsia have been ascribed to vagal dysfunction. We investigated whether vagal stimulation by sham feeding would improve meal-induced gastric motor function in these patients. Fourteen healthy volunteers and 14 functional dyspepsia patients underwent a drink test twice, once with and once without simultaneous sham feeding. After ingesting 500 mL clear meat soup (20 kcal, 37 °C) in 4 min, sham feeding was performed for 10 min by chewing a sugar-containing chewing gum while spitting out saliva. Using two- and three-dimensional ultrasound, antral motility index (contraction amplitude × frequency) and intragastric volumes were estimated. Without sham feeding, functional dyspepsia patients had lower motility index than healthy volunteers (area under curve 8.0 ± 1.2 vs 4.4 ± 1.0 min⁻¹, P  =   0.04). In functional dyspepsia patients, but not in healthy volunteers, motility index increased and intragastric volume tended to increase by sham feeding ( P  = 0.04 and P  = 0.06 respectively). The change in motility index was negatively correlated to the change in pain score ( r  = −0.59, P  = 0.007). In functional dyspepsia patients, vagal stimulation by sham feeding improves antral motility in response to a soup meal. The result supports the view that impaired vagal stimulation is implicated in the pathogenesis of gastric motility disturbances in functional dyspepsia.     

15.

Lower postprandial gastric volume response in diabetic patients with vagal neuropathy   总被引：4，自引：0，他引：4  

K. A. Undeland  T. Hausken  S. Aanderud  & A. Berstad 《Neurogastroenterology and motility》1997,9(1):19-24

Poor relaxation in the stomach after a meal may contribute to disturbed gastric emptying and abdominal discomfort in patients with diabetes mellitus. In this study we aimed to compare barostat-recorded postprandial volume responses in these patients to those in healthy controls, and to study the relationship between the proximal volume responses, antral filling and vagal neuropathy.
We compared 14 consecutively recruited patients with type 1 diabetes mellitus (DM) to 18 healthy controls (HC) with respect to meal-induced gastric volume response assessed by a barostat, antral area recorded by ultrasound, and vagal tone assessed by respiratory sinus arrhythmia (RSA).
Meal-induced volume repsponse of the proximal stomach (area under time–volume curve 0–30 min) was significantly (P = 0.04) lower in DM than in HC, 49.4 min.mL ± 60.7 vs. 114.9 min.mL ± 100.8. Antral area was significantly larger in DM than in HC, both fasting (4.3 cm² ± 1.9 vs. 3.0 cm² ± 0.9) and 10 min after ingestion of meat soup (11.8 cm² ± 3.4 vs. 8.8 cm² ± 2.9), P = 0.03 and P = 0.02, respectively. Vagal tone was significantly (P = 0.01) lower in DM than in HC, 3.7 beats min⁻¹ ± 2.3 vs. 6.1 beats min⁻¹ ± 2.2. No significant correlation was observed between the proximal volume responses and antral widening. Maximal gastric volume response correlated significantly with vagal tone (r = 0.77, P = 0.002). Conclusions: patients with diabetes mellitus type 1 have impaired meal-induced volume response, possibly as a consequence of reduced vagal tone.     

16.

19Electrogastrography differentiates enteric myopathy from neuropathy in adults with severe motility disorders of the gut     

ABID S  & LINDBERG G 《Neurogastroenterology and motility》2006,18(6):485-486

Background:  Chronic intestinal pseudo-obstruction, enteric dysmotility and slow transit constipation are severe motility disorders of the gut that usually are associated with an underlying enteric neuropathy or myopathy. Electrogastrography (EGG) is a non-invasive technique that records gastric myoelectric activity.
Aim of the study:  To determine whether EGG can differentiate enteric myopathy from neuropathy as the primary pathology in patients with severe motility disorders of the gut.
Material and methods:  This is a retrospective analysis of patients with various motility disorders of the gut that underwent full thickness small bowel biopsy. A single bipolar channel measured the EGG. The ability of EGG to differentiate between myopathy and neuropathy was tested by comparing 21 variables from EGG.
Results:  A total of 38 patients, 35 (92%) females, mean age 42 ± 13 years, were analysed. Twenty patients had enteric dysmotility (19 with neuropathy and one with myopathy), 12 had slow transit constipation (10 with neuropathy and two with myopathy), and six had chronic intestinal pseudo-obstruction (three with neuropathy and three with myopathy). Patients with myopathy showed higher percentage of fasting time with DF in bradygastric and tachygastric frequency bands and a higher postprandial DF (Table) than did patients with neuropathic motility disorders.
Conclusions:  Patients with visceral myopathy exhibited more arrhythmia during fasting and a higher DF following the test meal and this indicates that myopathies are associated with more electrical disturbances than neuropathies. EGG may be considered for differentiating between these two disease entities.
 

     

17.

Visceral perceptions and gastric myoelectrical activity in healthy women and in patients with bulimia nervosa     

K. L. KOCH  S. BINGAMAN  L. TAN  & R. M. STERN 《Neurogastroenterology and motility》1998,10(1):3-10

Bulimia nervosa remains a common eating disorder in young women. Little is known about upper gastrointestinal symptoms or gastric motility in patients with bulimia nervosa. The aim of this study was to measure gastric myoelectrical activity and hunger/satiety and stomach emptiness/fullness before and after a non-nutrient water load and solid-phase gastric emptying in hospitalized patients with bulimia nervosa (n = 12) and in healthy women (n = 13). Gastric myoelectrical activity was measured by means of cutaneous electrodes; visual analogue scales were used to measure perceptions of hunger/satiety and stomach emptiness/fullness. Before and after a standard water load the bulimia patients reported significantly greater stomach fullness and satiety compared with control subjects (P < 0.01). The percentage of gastric myoelectrical power in the normal 3 cpm range was significantly less in bulimics compared with controls. Power in the 1–2 cpm bradygastria range was significantly greater in bulimia patients before and after the water load compared with the control subjects (P < 0.05). Solid-phase gastric emptying studies using radio-isotope-labelled scrambled eggs showed the lag phase was shortened in the bulimic patients (16 ± 4 min vs 31 ± 4 min in controls, P < 0.01), but the percentage of meal emptied at 2 h was similar to control values. In conclusion: bulimia patients had exaggerated perceptions of stomach fullness and satiety in response to water; and abnormal gastric myoelectrical activity and accelerated lag phase of gastric emptying were objective stomach abnormalities detected in hospitalized patients with bulimia nervosa.     

18.

Discrimination of irritable bowel syndrome by non-linear analysis of 24-h jejunal motility   总被引：1，自引：0，他引：1  

WACKERBAUER    SCHMIDT    WIDMER    PFEIFFER    MORFILL  & KAESS 《Neurogastroenterology and motility》1998,10(4):331-337

Conventional analysis of ambulatory long-term manometry of the small intestine has revealed abnormalities in patients with the irritable bowel syndrome (IBS). The aim was to use methods from non-linear dynamics, in particular the concepts of symbolic dynamics and entropy, in order to discriminate motility in IBS from healthy subjects. 24-h jejunal motility was recorded in 30 IBS patients and 30 healthy subjects. Computerized analysis of contraction amplitudes and intercontractile intervals was performed. Both time series were analysed by symbolic dynamics and entropy to quantify the degree of randomness inherent in the signal. During phase II IBS patients exhibited significantly increased entropies for the intercontractile intervals (IBS: 0.978 ± 0.016, C: 0.965 ± 0.020, P  = 0.004) and for the contraction amplitudes (IBS: 0.978 ± 0.008, C: 0.970 ± 0.026, P  = 0.05) compared with healthy subjects. In addition, a significantly increased mean contraction amplitude (mmHg) was found in patients (IBS: 25.2 ± 4.8, C: 22.2 ± 3.1, P  = 0.003). Considering a combination of both parameters, a diagnostic accuracy of 82% was achieved. We conclude that phase II motility of the small intestine is more random in IBS than in health. Symbolic dynamics seems to be a promising new concept for the analysis of long-term gastrointestinal motility recordings.     

19.

Spatio-temporal analysis reveals aberrant linkage among sequential propagating pressure wave sequences in patients with symptomatically defined obstructed defecation     

p. g.  dinning  m. m.  szczesniak & i. j.  cook 《Neurogastroenterology and motility》2009,21(9):945-e75

Abstract  Available evidence implicates abnormal colonic contractility in patients suffering from constipation. Traditional analysis of colonic manometry focuses on the frequency, extent and amplitude of propagating sequences (PS). We tested the hypotheses that the spatio-temporal linkage among sequential PSs exists throughout the healthy human colon and is disrupted during constipation. In eight patients with severe constipation and eight healthy volunteers, we recorded colonic pressures from 16 regions (caecum–rectum) for 24 h. Sequential PSs were regionally linked if the two PSs originated from different colonic regions but the segments of colon traversed by each PS overlapped. In order to determine whether this linkage occurred by chance, a computer program was used to randomly rearrange all PSs in time. Data were re-analysed to compare regional linkage between randomly re-ordered PSs (expected) and the natural distribution of PSs (observed). In controls the observed regional linkage (82.5 ± 9.0%) was significantly greater than the expected value (60.5 ± 4.3%; P  = 0.0001). In patients the observed and expected regional linkage did not differ. The (observed − expected) delta value of regional linkage in controls was significantly greater than in patients (21.7 ± 8.5% vs −2.3 ± 7.0%; P  = 0.01). Regional linkage among sequential PSs in the healthy colon appears to be a real phenomenon and this linkage is lost in patients with constipation. Regional linkage may be important for normal colonic transit and loss of linkage might have pathophysiological relevance to and provide a useful biomarker of severe constipation.     

20.

Prolonged duodenal acid perfusion and dyspeptic symptom occurrence in healthy volunteers     

m.  di stefano  †  r.  vos  t.  vanuytsel  j.  janssens & j.  tack 《Neurogastroenterology and motility》2009,21(7):712-e40

Abstract  The pathophysiology of functional dyspepsia (FD) is unknown and several mechanisms associated with specific symptom patterns have been recently proposed. Increased duodenal acid exposure has been supposed to be associated with nausea, but recently an increase of severity of several dyspeptic symptoms was noted in a subset of dyspeptic patients. As its pathogenetic role is still unclear, we evaluated an involvement of duodenal acid exposure in symptom generation by inducing a hyperacidity status of the duodenum. Twelve young adult healthy volunteers in a randomized, double-blind protocol, underwent duodenal acid (0.2 N, 5 mL min⁻¹) or saline perfusion, antropyloroduodenal manometry and duodenal pH monitoring both during fasting and postprandially. Every 15 min, severity of discomfort, fullness, bloating, belching, nausea, heartburn, epigastric burning, satiety and pain were evaluated by visual analogue scale. During acid perfusion, symptom scores for discomfort, bloating, nausea, epigastric burning were significantly higher ( P  < 0.01) compared to saline. Postprandial antral motility index was lower (2.96 ± 1.8 vs 3.62 ± 1.8, P  = 0.01) and jejunal motility index higher (4.87 ± 1.0 vs 4.37 ± 1.4, P  = 0.01) during acid perfusion. Occurrence and duration of phases III of the migrating motor complex showed no difference. Duodenal acid perfusion causes a sensitization to dyspeptic symptoms and induces antral hypomotility and jejunal hypercontractility. Through these mechanisms, increased duodenal acid exposure may play a role in the pathophysiology of FD symptoms.     

Vagal activation by sham feeding improves gastric motility in functional dyspepsia

Abstract  Antral hypomotility and impaired gastric accommodation in patients with functional dyspepsia have been ascribed to vagal dysfunction. We investigated whether vagal stimulation by sham feeding would improve meal-induced gastric motor function in these patients. Fourteen healthy volunteers and 14 functional dyspepsia patients underwent a drink test twice, once with and once without simultaneous sham feeding. After ingesting 500 mL clear meat soup (20 kcal, 37 °C) in 4 min, sham feeding was performed for 10 min by chewing a sugar-containing chewing gum while spitting out saliva. Using two- and three-dimensional ultrasound, antral motility index (contraction amplitude × frequency) and intragastric volumes were estimated. Without sham feeding, functional dyspepsia patients had lower motility index than healthy volunteers (area under curve 8.0 ± 1.2 vs 4.4 ± 1.0 min⁻¹, P  =   0.04). In functional dyspepsia patients, but not in healthy volunteers, motility index increased and intragastric volume tended to increase by sham feeding ( P  = 0.04 and P  = 0.06 respectively). The change in motility index was negatively correlated to the change in pain score ( r  = −0.59, P  = 0.007). In functional dyspepsia patients, vagal stimulation by sham feeding improves antral motility in response to a soup meal. The result supports the view that impaired vagal stimulation is implicated in the pathogenesis of gastric motility disturbances in functional dyspepsia.     

Lower postprandial gastric volume response in diabetic patients with vagal neuropathy

Poor relaxation in the stomach after a meal may contribute to disturbed gastric emptying and abdominal discomfort in patients with diabetes mellitus. In this study we aimed to compare barostat-recorded postprandial volume responses in these patients to those in healthy controls, and to study the relationship between the proximal volume responses, antral filling and vagal neuropathy.
We compared 14 consecutively recruited patients with type 1 diabetes mellitus (DM) to 18 healthy controls (HC) with respect to meal-induced gastric volume response assessed by a barostat, antral area recorded by ultrasound, and vagal tone assessed by respiratory sinus arrhythmia (RSA).
Meal-induced volume repsponse of the proximal stomach (area under time–volume curve 0–30 min) was significantly (P = 0.04) lower in DM than in HC, 49.4 min.mL ± 60.7 vs. 114.9 min.mL ± 100.8. Antral area was significantly larger in DM than in HC, both fasting (4.3 cm² ± 1.9 vs. 3.0 cm² ± 0.9) and 10 min after ingestion of meat soup (11.8 cm² ± 3.4 vs. 8.8 cm² ± 2.9), P = 0.03 and P = 0.02, respectively. Vagal tone was significantly (P = 0.01) lower in DM than in HC, 3.7 beats min⁻¹ ± 2.3 vs. 6.1 beats min⁻¹ ± 2.2. No significant correlation was observed between the proximal volume responses and antral widening. Maximal gastric volume response correlated significantly with vagal tone (r = 0.77, P = 0.002). Conclusions: patients with diabetes mellitus type 1 have impaired meal-induced volume response, possibly as a consequence of reduced vagal tone.     

19Electrogastrography differentiates enteric myopathy from neuropathy in adults with severe motility disorders of the gut

Background:  Chronic intestinal pseudo-obstruction, enteric dysmotility and slow transit constipation are severe motility disorders of the gut that usually are associated with an underlying enteric neuropathy or myopathy. Electrogastrography (EGG) is a non-invasive technique that records gastric myoelectric activity.
Aim of the study:  To determine whether EGG can differentiate enteric myopathy from neuropathy as the primary pathology in patients with severe motility disorders of the gut.
Material and methods:  This is a retrospective analysis of patients with various motility disorders of the gut that underwent full thickness small bowel biopsy. A single bipolar channel measured the EGG. The ability of EGG to differentiate between myopathy and neuropathy was tested by comparing 21 variables from EGG.
Results:  A total of 38 patients, 35 (92%) females, mean age 42 ± 13 years, were analysed. Twenty patients had enteric dysmotility (19 with neuropathy and one with myopathy), 12 had slow transit constipation (10 with neuropathy and two with myopathy), and six had chronic intestinal pseudo-obstruction (three with neuropathy and three with myopathy). Patients with myopathy showed higher percentage of fasting time with DF in bradygastric and tachygastric frequency bands and a higher postprandial DF (Table) than did patients with neuropathic motility disorders.
Conclusions:  Patients with visceral myopathy exhibited more arrhythmia during fasting and a higher DF following the test meal and this indicates that myopathies are associated with more electrical disturbances than neuropathies. EGG may be considered for differentiating between these two disease entities.
 

     

17.

Visceral perceptions and gastric myoelectrical activity in healthy women and in patients with bulimia nervosa     

K. L. KOCH  S. BINGAMAN  L. TAN  & R. M. STERN 《Neurogastroenterology and motility》1998,10(1):3-10

Bulimia nervosa remains a common eating disorder in young women. Little is known about upper gastrointestinal symptoms or gastric motility in patients with bulimia nervosa. The aim of this study was to measure gastric myoelectrical activity and hunger/satiety and stomach emptiness/fullness before and after a non-nutrient water load and solid-phase gastric emptying in hospitalized patients with bulimia nervosa (n = 12) and in healthy women (n = 13). Gastric myoelectrical activity was measured by means of cutaneous electrodes; visual analogue scales were used to measure perceptions of hunger/satiety and stomach emptiness/fullness. Before and after a standard water load the bulimia patients reported significantly greater stomach fullness and satiety compared with control subjects (P < 0.01). The percentage of gastric myoelectrical power in the normal 3 cpm range was significantly less in bulimics compared with controls. Power in the 1–2 cpm bradygastria range was significantly greater in bulimia patients before and after the water load compared with the control subjects (P < 0.05). Solid-phase gastric emptying studies using radio-isotope-labelled scrambled eggs showed the lag phase was shortened in the bulimic patients (16 ± 4 min vs 31 ± 4 min in controls, P < 0.01), but the percentage of meal emptied at 2 h was similar to control values. In conclusion: bulimia patients had exaggerated perceptions of stomach fullness and satiety in response to water; and abnormal gastric myoelectrical activity and accelerated lag phase of gastric emptying were objective stomach abnormalities detected in hospitalized patients with bulimia nervosa.     

18.

Discrimination of irritable bowel syndrome by non-linear analysis of 24-h jejunal motility   总被引：1，自引：0，他引：1  

WACKERBAUER    SCHMIDT    WIDMER    PFEIFFER    MORFILL  & KAESS 《Neurogastroenterology and motility》1998,10(4):331-337

Conventional analysis of ambulatory long-term manometry of the small intestine has revealed abnormalities in patients with the irritable bowel syndrome (IBS). The aim was to use methods from non-linear dynamics, in particular the concepts of symbolic dynamics and entropy, in order to discriminate motility in IBS from healthy subjects. 24-h jejunal motility was recorded in 30 IBS patients and 30 healthy subjects. Computerized analysis of contraction amplitudes and intercontractile intervals was performed. Both time series were analysed by symbolic dynamics and entropy to quantify the degree of randomness inherent in the signal. During phase II IBS patients exhibited significantly increased entropies for the intercontractile intervals (IBS: 0.978 ± 0.016, C: 0.965 ± 0.020, P  = 0.004) and for the contraction amplitudes (IBS: 0.978 ± 0.008, C: 0.970 ± 0.026, P  = 0.05) compared with healthy subjects. In addition, a significantly increased mean contraction amplitude (mmHg) was found in patients (IBS: 25.2 ± 4.8, C: 22.2 ± 3.1, P  = 0.003). Considering a combination of both parameters, a diagnostic accuracy of 82% was achieved. We conclude that phase II motility of the small intestine is more random in IBS than in health. Symbolic dynamics seems to be a promising new concept for the analysis of long-term gastrointestinal motility recordings.     

19.

Spatio-temporal analysis reveals aberrant linkage among sequential propagating pressure wave sequences in patients with symptomatically defined obstructed defecation     

p. g.  dinning  m. m.  szczesniak & i. j.  cook 《Neurogastroenterology and motility》2009,21(9):945-e75

Abstract  Available evidence implicates abnormal colonic contractility in patients suffering from constipation. Traditional analysis of colonic manometry focuses on the frequency, extent and amplitude of propagating sequences (PS). We tested the hypotheses that the spatio-temporal linkage among sequential PSs exists throughout the healthy human colon and is disrupted during constipation. In eight patients with severe constipation and eight healthy volunteers, we recorded colonic pressures from 16 regions (caecum–rectum) for 24 h. Sequential PSs were regionally linked if the two PSs originated from different colonic regions but the segments of colon traversed by each PS overlapped. In order to determine whether this linkage occurred by chance, a computer program was used to randomly rearrange all PSs in time. Data were re-analysed to compare regional linkage between randomly re-ordered PSs (expected) and the natural distribution of PSs (observed). In controls the observed regional linkage (82.5 ± 9.0%) was significantly greater than the expected value (60.5 ± 4.3%; P  = 0.0001). In patients the observed and expected regional linkage did not differ. The (observed − expected) delta value of regional linkage in controls was significantly greater than in patients (21.7 ± 8.5% vs −2.3 ± 7.0%; P  = 0.01). Regional linkage among sequential PSs in the healthy colon appears to be a real phenomenon and this linkage is lost in patients with constipation. Regional linkage may be important for normal colonic transit and loss of linkage might have pathophysiological relevance to and provide a useful biomarker of severe constipation.     

20.

Prolonged duodenal acid perfusion and dyspeptic symptom occurrence in healthy volunteers     

m.  di stefano  †  r.  vos  t.  vanuytsel  j.  janssens & j.  tack 《Neurogastroenterology and motility》2009,21(7):712-e40

Abstract  The pathophysiology of functional dyspepsia (FD) is unknown and several mechanisms associated with specific symptom patterns have been recently proposed. Increased duodenal acid exposure has been supposed to be associated with nausea, but recently an increase of severity of several dyspeptic symptoms was noted in a subset of dyspeptic patients. As its pathogenetic role is still unclear, we evaluated an involvement of duodenal acid exposure in symptom generation by inducing a hyperacidity status of the duodenum. Twelve young adult healthy volunteers in a randomized, double-blind protocol, underwent duodenal acid (0.2 N, 5 mL min⁻¹) or saline perfusion, antropyloroduodenal manometry and duodenal pH monitoring both during fasting and postprandially. Every 15 min, severity of discomfort, fullness, bloating, belching, nausea, heartburn, epigastric burning, satiety and pain were evaluated by visual analogue scale. During acid perfusion, symptom scores for discomfort, bloating, nausea, epigastric burning were significantly higher ( P  < 0.01) compared to saline. Postprandial antral motility index was lower (2.96 ± 1.8 vs 3.62 ± 1.8, P  = 0.01) and jejunal motility index higher (4.87 ± 1.0 vs 4.37 ± 1.4, P  = 0.01) during acid perfusion. Occurrence and duration of phases III of the migrating motor complex showed no difference. Duodenal acid perfusion causes a sensitization to dyspeptic symptoms and induces antral hypomotility and jejunal hypercontractility. Through these mechanisms, increased duodenal acid exposure may play a role in the pathophysiology of FD symptoms.     

Visceral perceptions and gastric myoelectrical activity in healthy women and in patients with bulimia nervosa

Bulimia nervosa remains a common eating disorder in young women. Little is known about upper gastrointestinal symptoms or gastric motility in patients with bulimia nervosa. The aim of this study was to measure gastric myoelectrical activity and hunger/satiety and stomach emptiness/fullness before and after a non-nutrient water load and solid-phase gastric emptying in hospitalized patients with bulimia nervosa (n = 12) and in healthy women (n = 13). Gastric myoelectrical activity was measured by means of cutaneous electrodes; visual analogue scales were used to measure perceptions of hunger/satiety and stomach emptiness/fullness. Before and after a standard water load the bulimia patients reported significantly greater stomach fullness and satiety compared with control subjects (P < 0.01). The percentage of gastric myoelectrical power in the normal 3 cpm range was significantly less in bulimics compared with controls. Power in the 1–2 cpm bradygastria range was significantly greater in bulimia patients before and after the water load compared with the control subjects (P < 0.05). Solid-phase gastric emptying studies using radio-isotope-labelled scrambled eggs showed the lag phase was shortened in the bulimic patients (16 ± 4 min vs 31 ± 4 min in controls, P < 0.01), but the percentage of meal emptied at 2 h was similar to control values. In conclusion: bulimia patients had exaggerated perceptions of stomach fullness and satiety in response to water; and abnormal gastric myoelectrical activity and accelerated lag phase of gastric emptying were objective stomach abnormalities detected in hospitalized patients with bulimia nervosa.     

Discrimination of irritable bowel syndrome by non-linear analysis of 24-h jejunal motility

Conventional analysis of ambulatory long-term manometry of the small intestine has revealed abnormalities in patients with the irritable bowel syndrome (IBS). The aim was to use methods from non-linear dynamics, in particular the concepts of symbolic dynamics and entropy, in order to discriminate motility in IBS from healthy subjects. 24-h jejunal motility was recorded in 30 IBS patients and 30 healthy subjects. Computerized analysis of contraction amplitudes and intercontractile intervals was performed. Both time series were analysed by symbolic dynamics and entropy to quantify the degree of randomness inherent in the signal. During phase II IBS patients exhibited significantly increased entropies for the intercontractile intervals (IBS: 0.978 ± 0.016, C: 0.965 ± 0.020, P  = 0.004) and for the contraction amplitudes (IBS: 0.978 ± 0.008, C: 0.970 ± 0.026, P  = 0.05) compared with healthy subjects. In addition, a significantly increased mean contraction amplitude (mmHg) was found in patients (IBS: 25.2 ± 4.8, C: 22.2 ± 3.1, P  = 0.003). Considering a combination of both parameters, a diagnostic accuracy of 82% was achieved. We conclude that phase II motility of the small intestine is more random in IBS than in health. Symbolic dynamics seems to be a promising new concept for the analysis of long-term gastrointestinal motility recordings.     

Spatio-temporal analysis reveals aberrant linkage among sequential propagating pressure wave sequences in patients with symptomatically defined obstructed defecation

Abstract  Available evidence implicates abnormal colonic contractility in patients suffering from constipation. Traditional analysis of colonic manometry focuses on the frequency, extent and amplitude of propagating sequences (PS). We tested the hypotheses that the spatio-temporal linkage among sequential PSs exists throughout the healthy human colon and is disrupted during constipation. In eight patients with severe constipation and eight healthy volunteers, we recorded colonic pressures from 16 regions (caecum–rectum) for 24 h. Sequential PSs were regionally linked if the two PSs originated from different colonic regions but the segments of colon traversed by each PS overlapped. In order to determine whether this linkage occurred by chance, a computer program was used to randomly rearrange all PSs in time. Data were re-analysed to compare regional linkage between randomly re-ordered PSs (expected) and the natural distribution of PSs (observed). In controls the observed regional linkage (82.5 ± 9.0%) was significantly greater than the expected value (60.5 ± 4.3%; P  = 0.0001). In patients the observed and expected regional linkage did not differ. The (observed − expected) delta value of regional linkage in controls was significantly greater than in patients (21.7 ± 8.5% vs −2.3 ± 7.0%; P  = 0.01). Regional linkage among sequential PSs in the healthy colon appears to be a real phenomenon and this linkage is lost in patients with constipation. Regional linkage may be important for normal colonic transit and loss of linkage might have pathophysiological relevance to and provide a useful biomarker of severe constipation.     

Prolonged duodenal acid perfusion and dyspeptic symptom occurrence in healthy volunteers

Abstract  The pathophysiology of functional dyspepsia (FD) is unknown and several mechanisms associated with specific symptom patterns have been recently proposed. Increased duodenal acid exposure has been supposed to be associated with nausea, but recently an increase of severity of several dyspeptic symptoms was noted in a subset of dyspeptic patients. As its pathogenetic role is still unclear, we evaluated an involvement of duodenal acid exposure in symptom generation by inducing a hyperacidity status of the duodenum. Twelve young adult healthy volunteers in a randomized, double-blind protocol, underwent duodenal acid (0.2 N, 5 mL min⁻¹) or saline perfusion, antropyloroduodenal manometry and duodenal pH monitoring both during fasting and postprandially. Every 15 min, severity of discomfort, fullness, bloating, belching, nausea, heartburn, epigastric burning, satiety and pain were evaluated by visual analogue scale. During acid perfusion, symptom scores for discomfort, bloating, nausea, epigastric burning were significantly higher ( P  < 0.01) compared to saline. Postprandial antral motility index was lower (2.96 ± 1.8 vs 3.62 ± 1.8, P  = 0.01) and jejunal motility index higher (4.87 ± 1.0 vs 4.37 ± 1.4, P  = 0.01) during acid perfusion. Occurrence and duration of phases III of the migrating motor complex showed no difference. Duodenal acid perfusion causes a sensitization to dyspeptic symptoms and induces antral hypomotility and jejunal hypercontractility. Through these mechanisms, increased duodenal acid exposure may play a role in the pathophysiology of FD symptoms.