Scintigraphic measurement of regional gut transit in idiopathic constipation

In this study, total gut transit and regional colonic transit in patients with idiopathic constipation were measured scintigraphically. Eight patients with severe constipation were studied, none of whom had evidence of abnormal function of the pelvic floor. 99mTc-radiolabeled Amberlite resin particles (average diameter, 1 mm; Sigma Chemical Co., St. Louis, MO) with a mixed meal were used to assess gastric emptying and small bowel transit; similar particles labeled with 111In were ingested in a coated capsule that dispersed in the ileocecal region. These were used to quantify colonic transit. Five healthy volunteers were also studied. Two patients showed delayed gastric emptying and two had slow small bowel transit. Seven of the eight patients had slow colonic transit. In five, delay affected the whole colon ("pancolonic inertia"); in two, transit in the ascending and transverse colon was normal, but solids moved through the left colon slowly. Mean colonic transit was also measured using radiopaque markers; this technique identified the patients with slow transit, as shown by measurements of overall colonic transit by simultaneous scintigraphy. However, estimated transit through the ascending and transverse colons was considerably shorter by the radiopaque marker technique. In conclusion, idiopathic constipation is characterized by either exaggerated reservoir functions of the ascending and transverse colons and/or impairment of propulsive function in the descending colon. Particle size may influence the result of regional colonic transit tests. Transit delays in other parts of the gut suggest that, in some patients, the condition may be a more generalized motor dysfunction.     

Decreased interstitial cell of cajal volume in patients with slow-transit constipation

BACKGROUND & AIMS: The cause of slow-transit constipation is incompletely understood. Recent observations suggest a central role for interstitial cells of Cajal in the control of intestinal motility. The aim of this study was to determine the volume of interstitial cells of Cajal in the normal sigmoid colon and in the sigmoid colon from patients with slow transit constipation. METHODS: Sigmoid colonic samples were stained with antibodies to protein gene product 9.5, c-Kit, and alpha-smooth muscle actin. Three-dimensional reconstruction of regions of interest was performed using consecutive images collected on a laser scanning confocal microscope and ANALYZE software. RESULTS: Volume of interstitial cells of Cajal was significantly decreased in all layers of sigmoid colonic specimens from patients with slow-transit constipation compared with normal controls. Neuronal structures within the colonic circular smooth muscle layer were also decreased. CONCLUSIONS: A decrease in the volume of interstitial cells of Cajal may play an important role in the pathophysiology of slow-transit constipation.     

Are colonic regular contractile frequency patterns in slow transit constipation a relevant pathophysiological phenomenon?

BACKGROUND: Pathogenesis of slow transit constipation still remains elusive. Some studies have shown several colonic motor abnormalities; however, it is not easy to understand the relative importance of the single ones. AIMS: Since it has been hypothesized that an excess of periodic distal motor activity may be of pathophysiological importance in patients with slow transit constipation, we evaluated regular colonic contractile frequencies in a homogeneous cohort of these patients. PATIENTS: A total of 26 female patients (age range 34 to 67 years) fulfilling the Rome II criteria for constipation entered the study. No patient had evidence of secondary forms of constipation and distal obstruction. METHODS: Twenty-four hour colonic manometric studies were obtained for each patient. Regular contractile patterns (with frequencies ranging from 2 to 8 cycles/min) were calculated for the entire recording period and in single colonic segments. RESULTS: Overall, regular patterns accounted for about 3% of the total colonic motor activity (average 30 min/day per subject), with the 3 cycles/min being the predominant contractile rhythm. Most of this activity was present in the sigmoid colon, accounting for >50% of the total amount of motility, and it was more prevalent than in the descending and transverse colon; no differences were revealed in the descending with respect to the transverse colon. No daily fluctuations of regular contractile activity, nor a cyclic pattern, nor migration between recording points were observed. CONCLUSIONS: Regular colonic frequency patterns are probably of minor pathophysiological importance in slow transit constipation, even in the light of the scant amount of such phenomena previously documented in healthy subjects.     

Delayed Colonic Transit in Spinal Cord-Injured Patients Measured by Indium-111 Amberlite Scintigraphy

Objective : Constipation is a major problem for patients with chronic spinal cord injury (SCI). However, it is not clear whether abnormal colonic transit is restricted to the rectosigmoid region or involves the entire colon. We assessed regional colonic transit with emphasis on the ascending and transverse segments in patients with chronic SCI and compared the results with those of controls using scintigraphic techniques. Methods : Seven patients with SCI below T1 and 10 control subjects were studied after oral ingestion of a capsule containing indium-111-labeled Amberlite (Sigma Chemical, St. Louis, MO) pellets. The capsule was coated with a pH-sensitive polymer that prevents disintegration until it reaches the Heocecal region. Assessments of the half-time of emptying and residence time of contents in ascending and transverse segments were made, as well as an assessment of the velocity of contents throughout the entire colon, including the descending colon. Results : A significantly slower half-time of emptying was found in SCI patients (ascending: 29 ± 27 hr in SCI, 6.81 ± 3.03 hr in controls, p < 0.01; ascending + transverse: 42 ± 12 hr in SCI, 15.3 ± 7.16 hr in controls, p < 0.01). The residence time of the median position of the contents was significantly prolonged in SCI patients (ascending: 31 ± 23 hr in SCI, 8.75 ± 4.68 hr in controls, P < 0.05; transverse: 26 ± 3 hr in SCI, 5.0 ± 4,4 hr in controls, P < 0.05). Overall, the velocity of the median position of contents throughout the entire colon was significantly lower in SCI (0.63 ± 0.33 cm/hr in SCI, 2.58 ± 1.20 cm/hr in controls, P < 0.001). Conclusions : Patients with chronic SCI have prolonged colonic transit that involves the entire colon. Hence, treatment of constipation in these patients may need to include prokinetic agents as well as local rectal maneuvers.     

Decreased interstitial cells of Cajal in the sigmoid colon of patients with slow transit constipation

Background and aims Slow transit constipation (STC) is a colonic motor disorder that is characterized by measurably delayed movement of materials through the colon. Although abnormalities in the neuronal networks of the colon have been demonstrated in patients with STC, the etiology of STC remains unclear. Interstitial cells of Cajal (ICC) have been shown to be the pacemaker cells of the intestine and have been implied in the pathogenesis of a number of gastrointestinal motility dysfunctions, including idiopathic STC. This study aimed to determine the normal distribution of ICC within the colon of the Chinese and also to determine if ICC are decreased in Chinese STC patients.Patients and methods Twelve patients with STC and eight age-matched normal controls were studied. Specimens of sigmoid colon were obtained immediately after resection. ICC were identified with a monoclonal antibody to c-kit by an indirect immunofluorescence method. Immunostained tissues were examined with a laser scanning confocal microscope and the area occupied by ICC was calculated with an image analysis system.Results ICC were located in the external muscle layers including myenteric plexus (MP) and submucosal border (SMB). Two types of Kit-positive ICC were observed: bipolar cells characterized by one or two long processes and multipolar cells characterized by long stellate processes extending in various directions. A higher percentage of ICC was present in the MP regions and circular muscle (CM) layers compared with the SMB and longitudinal muscle (LM) layers. Tissues from STC patients showed a considerable decrease in the number of ICC located in the four regions (ICC-LM, ICC-MP, ICC-CM, ICC-SMB), especially the ICC-SMB, in which ICC almost completely disappeared.Conclusions Similar distribution of ICC was observed in the normal sigmoid colon of the Chinese. Decreased area of c-kit+ ICC may play an important role in the pathophysiology of STC. It remains to be determined whether the loss of ICC is primary or secondary to another lesion.     

Decreased density of interstitial cells of Cajal and neuronal cells in patients with slow-transit constipation and acquired megacolon

BACKGROUND: The pathophysiology of constipation is not clearly identified as yet, and the interstital cells of Cajal (ICC), known to generate the slow wave activity and to be involved in intestinal neurotransmission and the enteric nervous system (ENS), are suspected to play an important role. The aims of the present study were to assess the distribution of ICC and neuronal cells of ENS in patients with slow-transit constipation and acquired megacolon. METHODS: Sigmoid colon specimens were obtained from patients who underwent colectomy due to slow-transit constipation (n = 10), acquired megacolon (n = 9) and non-obstructive colon cancer (n = 10) as a control group. The ICC were visualized by c-Kit immunohistochemistry and neuronal cells of the ENS were demonstrated by protein gene product (PGP) 9.5. Density of cells stained by c-Kit and PGP 9.5 was calculated as percent area (area stained/area of X-Y plane) x 100, when images were collected at a magnification of x40 objective, with maximum area examined in the horizontal X-Y plane of 400 microm x 400 microm using an image analyzer. RESULTS: The densities of ICC and PGP 9.5 reactive neuronal structures were significantly decreased in all layers of sigmoid colon specimens in patients with slow-transit constipation and acquired megacolon, compared with that of the control group. However, there was no statistically significant difference in either the density of ICC or that of neuronal structures between the patients with slow-transit constipation and acquired megacolon. CONCLUSIONS: Slow-transit constipation and acquired megacolon were associated with alteration of ICC and neuronal cells of ENS in the sigmoid colon.     

Towards a relatively inexpensive, noninvasive, accurate test for colonic motility disorders.

Currently available clinical tests of colonic transit, such as the radiopaque marker method, are useful to detect delayed transit but may be less sensitive for rapid transit. The aim of this study was to develop a relatively inexpensive, noninvasive, accurate test of colonic transit using selected scintigraphic observations within the first 24 hours after ingestion of a pH-sensitive, methacrylate-coated, delayed-release capsule containing 111In-labeled resin pellets. The authors' previously published colonic transit data on 22 healthy subjects, 9 patients with diarrhea-predominant irritable bowel syndrome, and 7 patients with idiopathic constipation and previously unpublished data on 4 patients with carcinoid diarrhea were analyzed. A logistic discriminant analysis was used to estimate the sensitivity and specificity of selected combinations or simple summaries of transit. Among combined transit summaries, the emptying rate of the proximal colon was significantly different between healthy and constipation groups; the geometric center of isotope in the colon at 4 hours was significantly greater in the diarrhea group than in healthy controls; the geometric center at 24 hours was significantly lower in the constipation group than in the other two groups. From the logistic discriminant analysis, simple summaries of transit also had significant discriminant value; these included the isotopic contents in the ascending, transverse, and descending colon at 4 hours and the counts in the ascending and transverse colon and stool at 24 hours. At 90% sensitivity, the specificity of the transverse colon counts at 4 hours was 79%, which is identical to the specificity of the proximal colon emptying rate, both adjusted for age. Thus, quantitation of isotopic counts in colonic regions on scans taken at 4 and 24 hours provides an accurate summary of colonic transit, with acceptable specificity at a high sensitivity in the detection of motility disorders of the colon.     

Symptoms and physiology in severe chronic constipation

Objective: Symptoms of constipation have been attributed to slow colon transit, irritable bowel syndrome (IBS), or pelvic floor dysfunction (PFD). Our aim was to determine the existence of symptom-based constipation subgroups and whether these correspond to differences in colonic transit and anorectal sensorimotor function. Methods: Constipated patients (n = 108) completed questionnaires, and underwent colon transit studies, anorectal manometry, and rectal sensory testing. Factor analysis of symptoms was performed. Factor-based symptom scores were correlated with physiological findings. Results: Three symptom factors were identified as compatible with slow colonic transit, IBS, and PFD. There was a significant correlation between the symptoms of slow transit and total and rectosigmoid colon transit. There were also significant correlations between both the IBS symptom score and the number of Manning criteria with measures of rectal hypersensitivity typical of IBS. Neither PFD symptom scores nor symptoms of straining correlated with any electromyographic or manometric measure of anal defecatory function or with rectosigmoid colon transit. Based on physiological testing patients were classified as slow transit, visceral hypersensitivity (typical of IBS), PFD, or no abnormalities found. As expected, slow-transit patients had symptoms of infrequent stools and patients with visceral hypersensitivity had an increased number of Manning criteria for IBS. Patients with PFD physiology and those with no detectable abnormalities had no specific symptoms. Conclusions: Three symptom-based subgroups for constipation were confirmed: slow transit, IBS, and PFD. Slow transit and IBS symptoms correlated with expected physiology. Conversely, PFD symptoms and physiology did not correlate.     

Short-term effects of magnetic sacral dermatome stimulation for idiopathic slow transit constipation: Sham-controlled, cross-over pilot study

Background and Aim: An increase in recto‐sigmoid colon activity through electrical stimulation of the sacral dermatomes has previously been reported. It has not been evaluated whether or not sacral dermatome stimulation has beneficial effects on constipation symptoms and anorectal function in constipated patients. Our aim was to evaluate short‐term effects of magnetic stimulation of the sacral dermatomes on constipation symptoms and anorectal function in patients with idiopathic slow transit constipation. Method: Fourteen patients with idiopathic slow transit constipation were enrolled. Constipation symptoms, stool form and anorectal function were assessed before treatment, and at 3 and 6 weeks of treatment. Six‐week treatment consisted of either a 3‐week period of sham treatment or a 3‐week period of magnetic stimulation of the S2‐S3 dermatomes, which was performed in a randomized cross‐over design. Results: During the stimulation period, the frequency score of spontaneous bowel movements decreased in eight of the 14 patients (2.9 [2–3]vs 1.4 [0–2]), whose threshold volumes for urge to defecate and maximum tolerable volumes were significantly greater than those of the non‐responders, and significantly decreased at the end of treatment. The degree of straining on defecation also significantly decreased in the responders. Responders had shorter right colonic transit time and longer left colonic transit time compared to the non‐responders. Sham treatment did not affect constipation symptoms, stool form and rectal sensation. Conclusion: Sacral dermatome stimulation may offer potential for therapeutic benefit for a subset of patients with idiopathic slow transit constipation, particularly constipated patients with rectal hyposensation or hindgut dysfunction.     

Loss of interstitial cells and a fibromuscular layer on the luminal side of the colonic circular muscle presenting as megacolon in an adult patient

BACKGROUND: Animal studies have shown that the neuromuscular structures on the luminal side of the colonic circular muscle coordinate circular muscle activity. These structures have been identified by electron microscopy in the normal human colon, but have never been thoroughly studied in patients with acquired intestinal hypoganglionosis. AIMS: To perform histological, immunocytochemical, and electron microscopic examinations of the colon of a patient with acquired intestinal hypoganglionosis presenting as megacolon. PATIENT: A 32 year old man with a one year history of constipation and abdominal distention, a massively dilated ascending and transverse colon, and a normal calibre rectum and descending and sigmoid colon. He had a high titre of circulating serum anti-neuronal nuclear antibodies. METHODS: Histology, immunocytochemistry (for neurofilaments, neurone specific enolase, synaptophysin, glial fibrillar acidic protein, S100 protein, and smooth muscle alpha-actin), and electron microscopic examinations on the resected colon. RESULTS: The number of ganglion cells and nerve trunks was decreased throughout the colon. Disruption of the neural network and a loss of interstitial cells of Cajal were observed on the luminal side of the circular muscle; in their place, the non-dilated colon contained a hypertrophic fibromuscular layer. CONCLUSIONS: Striking architectural alterations occurred at the site regarded as the source of the coordination of colonic circular muscle activity in an adult patient with acquired intestinal hypoganglionosis presenting as megacolon.     

Fiber intake and colonic transit time in functional constipated patients

BACKGROUND: Patients with functional constipation presenting no response to treatment using fibers supplement represents important clinical issue. AIMS: To evaluate the relations among the amount of ingested fiber, the constipation intensity and the colonic transit time in patients with functional constipation. METHODS: We evaluated 30 patients, presenting no response to treatment using fibers supplement, and 18 healthy volunteers conducting individual inquiry into fibers intake, constipation intensity and the total and segmental colonic transit evaluation using radiopaque markers. RESULTS: In the constipated, despite the good level of fiber intake (26.3 +/- 12.9 g, constipated x 9.3 +/- 5,2 g, control), the symptoms of constipation was serious (score = 21.3 +/- 4.07). Mean total colonic transit was 58.8h. The colonic transit was slower in the constipated group (41.0 +/- 22.8 hours, constipated x 21.8 +/- 18.5h, control). In constipated patients with slow colonic transit (>58.8h) there were colonic inertia (eight), outlet constipation (one) and slow transit in left colon (one), and among constipated patients with normal colonic transit (<58.8h), there were isolated slow transit, in the right colon (nine), left colon (three) and in the rectosigmoid segment (eight). There were no relation among the amount of ingested fiber, constipation intensity and the colon transit. CONCLUSIONS: In the functional constipation the gravity of symptoms does not depend only on the dietary fibers intake, which is not the only responsible for the differences in the colonic transit. The colonic transit can differentiate normal from constipated patients and, among them, those with altered transit that demand approaches distinct of fiber supplementation.     

Regulation of the enteric nervous system in the colon of patients with slow transit constipation

BACKGROUND/AIMS: The cause of impaired motility in patients with slow transit constipation is unknown. To clarify the physiological significance of cholinergic, adrenergic, non-adrenergic non-cholinergic inhibitory nerves in the colon of patients with slow transit constipation, we investigated the enteric nerve responses on lesional and normal bowel segments derived from patients with slow transit constipation and patients who underwent colon resection for colonic cancers. METHODOLOGY: Twenty preparations were taken from the lesional colon of 6 patients with slow transit constipation (2 men and 4 women, aged 23 to 68 years, with a mean age of 44.0 years). Thirty-six preparations were taken from the normal colon of 12 patients with colonic cancer (6 men and 6 women, aged 40 to 60 years, with a mean age of 52.2 years). A mechanographic technique was used to evaluate in vitro muscle responses to acetylcholine, adrenalin, electrical field stimulation of adrenergic and cholinergic nerves before and after treatment with various autonomic nerve blockers. RESULTS: The contraction reaction to acetylcholine in the colon with slow transit constipation was significantly weaker than in the normal colon (P < 0.01). The relaxation reaction to adrenalin in the colon with slow transit constipation was stronger than in the normal colon. The colon with slow transit constipation was more strongly innervated by non-adrenergic non-cholinergic inhibitory nerves than the normal colon, significantly (P < 0.05). CONCLUSIONS: These findings suggest that a decrease of cholinergic nerve and an increase of non-adrenergic non-cholinergic inhibitory nerve play an important role in the impaired motility observed in the colon of patients with slow transit constipation.     

Dynamic scanning defines a colonic defect in severe idiopathic constipation.

A technique is described in which a chemical stimulus applied to the mucosa of the right colon is used to assess colonic motor function. Peroral intubation of the right colon was achieved using a fine polyvinylchloride (PVC) tube. Bisacodyl was used to initiate colonic motor activity, and colonic transit was monitored using 99mTc-DPTA and a gamma camera. In normal subjects there was rapid movement of the radiopharmaceutical from the right colon to the rectum. In patients with severe idiopathic constipation, a spectrum of colonic abnormality was observed from slow transit involving the rectum and sigmoid only to slow transit involving the whole colon. The hepatic flexure to rectum transit time for the 'head of the isotope column' in normals ranged from 1-10 minutes (mean 5.3 minutes), whereas in patients the transit time was 14-25 minutes in four patients and radioisotope did not reach the rectum by two hours in three other patients (controls v patients, p less than 0.01). Patients also showed relatively impaired transport of the isotope 'mass'. This technique has shown that the normal colon is capable of rapid effective transport in response to a standard stimulus, and that patients with severe idiopathic constipation have a definable colonic motor disorder.     

Role of opiate receptors in the regulation of colonic transit

The effects of morphine and the opiate antagonist naloxone on human colonic transit were investigated. In a crossover, double-blind fashion, two groups of 6 normal volunteers were studied using colonic transit scintigraphy during the administration of a test drug or control. The test drugs were morphine (0.1 mg/kg every 6 h s.c.) or naloxone (0.8 mg every 6 h s.c.); control was saline (1 ml every 6 h s.c.). Morphine significantly delayed transit in the cecum and ascending colon (p less than 0.05), slowed the progression of the geometric center (p less than 0.01), and decreased the number of bowel movements per 48 h (p less than 0.005). Naloxone accelerated transit in the transverse colon and rectosigmoid colon (p less than 0.05) and accelerated the progression of the geometric center (p less than 0.05), but had no effect on the number of bowel movements per 48 h (p greater than 0.05). These results suggest that narcotic analgesics may cause constipation in part by slowing colonic transit in the proximal colon and by inhibiting defecation. Acceleration of transit by naloxone suggests that endogenous opiate peptides may play an inhibitory role in the regulation of human colonic transit.     

内吗啡肽对泻剂结肠大鼠结肠肌电活动的影响

目的研究内吗啡肽对泻剂结肠大鼠结肠肌电活动的影响,探讨慢传输性便秘的发病机制。方法建立泻剂结肠动物模型,测定内吗啡肽1和内吗啡肽2对大鼠结肠肌电活动的影响。结果泻剂组大鼠结肠慢波频率和振幅分别为(28.19±7.51)次/min和(0.076±0.018)mV,与对照组比较[(36.05±8.94次/min)和(0.600±0.310)mV]明显降低;内吗啡肽1、内吗啡肽2以浓度依赖方式抑制泻剂结肠的慢波肌电活动,振幅明显降低,频率[(2 8.18±7.51)次/min3无明显变化,内吗啡肽1的作用强于内吗啡肽2。注射内吗啡肽不能阻断乙酰胆碱对结肠的兴奋作用。阿片受体拮抗剂纳洛酮(naloxone)能逆转内吗啡肽的抑制作用。结论内吗啡肽参与了泻剂结肠大鼠结肠肌电活动和结肠动力的调控,可能是慢传输性便秘发病的重要因素之一。     

Patterns of Colonic Transit in Chronic Idiopathic Constipation

Rectosigmoid motility, anal manometry, and radiopaque marker studies have suggested the presence of several patterns of altered colonic transit in patients with chronic idiopathic constipation. Colonic transit scintigraphy was used to evaluate 23 constipated patients. After oral passage of a tube to the cecum, 50 microCi of 111In-diethylenetriaminepentaaceticacid (111In-DTPA) were instilled, and abdominal images were obtained for 48 h with a gamma camera. The 95% confidence limit for the geometric center in normals at 24 h was used as a criterion to differentiate patients with colonic inertia from those with functional rectosigmoid obstruction. In patients with functional rectosigmoid obstruction, colonic transit was essentially normal. In colonic inertia, transit was delayed in the cecum and ascending colon, hepatic flexure, and transverse colon. These two distinct patterns of colonic transit may have different pathogenetic and therapeutic implications.     

An endoscopic method to study the relationship between bowel habit and motility of the ascending and sigmoid colon

Endoscopic retrograde bowel insertion (ERBI), a new method, offers rapid access to the entire colon for pressure sensors. The authors measured the pressure of both the ascending colon and the sigmoid colon and related them to the bowel habits of the subjects. The following groups were studied: control subjects, patients with diarrhea-dominant irritable bowel syndrome, patients with constipation-dominant irritable bowel syndrome, and patients with right-sided diverticular disease of the colon. In patients with irritable bowel syndrome with diarrhea or constipation, colonic motility indices (CMIs) showed a so-called "paradoxical motility" pattern. In patients with right-sided diverticular disease, the CMI was higher in the ascending colon than in the sigmoid colon. The pattern of CMIs for diverticular disease and irritable bowel syndrome varied inversely in the ascending colon and in the sigmoid colon with diarrhea and constipation. These results suggest that the mechanisms of altered bowel habits in patients with these diseases are quite different.     

Postprandial colonic transit and motor activity in chronic constipation

The aim of this study was to correlate colonic motility and transit in patients with constipation and symptoms of the irritable bowel syndrome. Studies were performed in 16 patients with constipation and compared with the results in 12 healthy subjects. Intraluminal pressure was measured with perfused catheter ports in the transverse colon, splenic flexure, and descending and sigmoid colon. Movement of the luminal contents was measured by following the movement of Technetium-99m-DTPA that was instilled as a bolus in the splenic flexure. In both healthy subjects and patients with constipation there was no movement of the intraluminal tracer and no increase in intraluminal pressure during fasting. After eating a meal, healthy subjects and one group of the constipated patients had an increase in the radioactive marker in the transverse colon (p less than 0.03) and in the sigmoid colon (p less than 0.03). The movement of the intraluminal contents was associated with a positive pressure gradient between the descending colon and the transverse and sigmoid colon. There was no retrograde movement of the intraluminal contents and no postprandial increase in intraluminal pressure in the second group of patients with constipation. In healthy subjects, propagating contractions, which were associated with the rapid movement of intraluminal contents, began 60 min after eating. There were no propagating contractions in patients with constipation. These studies suggest that (a) the movement of intraluminal contents in healthy and constipated patients is determined by the postprandial pressure gradients within the colon, and (b) the propagating contraction is necessary for a normal bowel habit.     

Prucalopride accelerates gastrointestinal and colonic transit in patients with constipation without a rectal evacuation disorder

BACKGROUND & AIMS: Prucalopride (PRU) is a selective benzofuran 5-hydroxytryptamine(4)-receptor agonist with gastrointestinal and colonic prokinetic activities. We evaluated the effects of PRU on gastrointestinal and colonic transit in patients with constipation. METHODS: Gastrointestinal and colonic transit were measured over 48 hours in 40 patients who fulfilled modified Rome I criteria for functional constipation. Patients had no evidence of a rectal evacuation disorder. Subjects were randomized to receive a daily dose of 2 or 4 mg PRU or placebo in a double-blind, parallel-group design. Each treatment lasted 7 days. The transit test was performed over the last 48 hours of the study. Effects on gastric emptying, small bowel transit, and colonic transit were analyzed using Kruskal-Wallis and Wilcoxon rank sum tests. RESULTS: Of 61 patients screened, 40 were eligible and randomized. Two patients withdrew because of adverse events. PRU accelerated overall gastric emptying and small bowel transit. PRU tended to accelerate overall colonic transit with significantly faster overall colonic transit and ascending colon emptying with the 4-mg dose. CONCLUSIONS: PRU accelerates transit through the stomach, small bowel, and colon in patients with constipation unassociated with a rectal evacuation disorder.     

大鼠胃肠道不同部位Cajal间质细胞与慢传输型便秘的关系

目的观察慢传输型便秘(slow transit constipation,STC)大鼠模型胃肠道Cajal间质细胞(interstitial cell of cajal,ICC)的分布特点与含量改变,全面评估ICC在STC发病机制中的作用。方法 24只健康Wistar大鼠随机分成便秘组和对照组,分别饲喂含复方苯乙哌啶的混悬液和生理盐水,每5 d记录1次大鼠大便粒数、大便干质量及大鼠体质量。饲养90 d后停药1周,测定胃肠道传输功能并通过免疫组化的方法测定ICC的特异性标志物c-kit+细胞在胃窦、小肠、结肠的分布情况与含量变化。结果便秘组日均粪便粒数少于对照组(P<0.01),平均每粒粪便质量大于对照组(P<0.05);便秘组首粒黑便排出时间长于对照组(P<0.05);与对照组比较,便秘组胃窦部位c-kit+细胞数量无明显变化(P>0.05)。而c-kit+细胞在便秘组大鼠小肠、结肠的数目均少于对照组(P<0.05)。结论在STC模型中,胃窦ICC变化不明显,小肠ICC数量有减少趋势,可能对STC有一定影响,结肠部位ICC数量明显减少,可能是慢传输型便秘大鼠的主要病理生理机制。