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1.
Acupuncture has been used for treating functional gastrointestinal (GI) disorders. Animal studies have demonstrated that acupuncture antagonized various stress-induced responses. We investigated the effects of electroacupuncture (EA) at ST-36 (Zusanli; lower limb) on stress-induced alteration of GI motor activities. Solid gastric emptying was significantly delayed by restraint stress (29.6±2.4%; n=7) compared to that of controls (60.0±2.5%; n=8). Delayed gastric emptying was significantly improved by EA at ST-36 (47.2±1.8%). Intracisternal (IC) injection of corticotropin releasing factor (CRF; 1 μg) delayed gastric emptying to 25.4±3.1%, which was also improved by EA at ST-36, to 53.0±7.1% (n=8). The stimulatory effect of EA on stress-induced delayed gastric emptying was abolished by atropine (17.6±1.9%) but not by guanethidine (42.2±2.3%). Colonic transit was significantly accelerated by restraint stress (GC=7.2±0.3; n=8) compared to that of controls (GC=5.2±0.2; n=8). Accelerated colonic transit was significantly reduced by EA at ST-36 (GC=4.9±0.3). IC injection of CRF accelerated colonic transit (GC=6.9±0.2), which was also normalized by EA at ST-36 (GC=4.7±0.2). The inhibitory effect of EA on stress-induced acceleration of colonic transit was not affected by guanethidine (GC=4.6±0.3). In conclusion, EA at ST-36 showed dual effects: stimulation of stress-induced delayed gastric emptying and inhibition of stress-induced acceleration of colonic transit. The stimulatory effect of EA on stress-induced delayed gastric emptying is mediated via cholinergic pathways. The inhibitory effect of EA on stress-induced acceleration of colonic transit is independent of the sympathetic pathway.  相似文献   

2.
BACKGROUND & AIMS: This study evaluated the effects of a partial 5-hydroxytryptamine (5-HT)(4) agonist, tegaserod, on gastric small bowel and colonic transit in constipation-predominant irritable bowel syndrome (IBS). METHODS: After a 1 week run-in period, 24 patients with constipation-predominant IBS were randomized to 1 week of tegaserod, 2 mg twice daily, or placebo treatment. Scintigraphic gastric emptying, small bowel transit, and colonic transit were determined before administration of study drug and after 1 week on the medication. Colonic transit was also measured using radiopaque markers and a single radiograph on day 5. RESULTS: Gastric emptying was unaltered by tegaserod. Proximal colonic filling at 6 hours, a measure of orocecal transit, was accelerated by tegaserod (70.4% +/- 1.3% [mean +/- SEM] vs. placebo, 46.4 +/- 1.9; P = 0.015). Proximal colonic emptying half-time and geometric center at 48 hours were also accelerated by tegaserod compared with baseline, but not compared with placebo. Mean colonic transit time was similar in both groups at baseline and after drug administration (tegaserod, 59.5 +/- 2.1 hours; placebo, 62.1 +/- 2.1 hours). CONCLUSIONS: Tegaserod accelerates orocecal transit, tends to accelerate colonic transit, and deserves further study in patients with constipation-predominant IBS.  相似文献   

3.
The effects of chilli on gastrointestinal transit (gastric emptying, orocaecal transit, whole gut transit) were evaluated in eight healthy volunteers. In each subject, gastrointestinal transit of a standard test meal was measured on two separate days. On one of these occasions, 20 g of chilli powder was added to the meal. Gastric emptying was quantified with a radioisotopic technique, orocaecal transit by measurement of breath hydrogen concentrations and whole gut transit by counting the number of radio-opaque markers in the stool. The rate of gastric emptying was slower (P less than 0.05) and whole gut transit was faster (P less than 0.02) after the meal containing chilli, compared with the other meal. There was no significant difference in orocaecal transit. These results show that ingestion of chilli is associated with significant effects on gastric emptying and intestinal transit.  相似文献   

4.
The effects of octreotide on regional motor function in the human gut are unclear. In a randomised, blinded study the effects of octreotide (50 micrograms, subcutaneously, three times daily) and placebo on gastric, small bowel, and colonic transit, and colonic motility and tone were assessed in 12 healthy volunteers whose colon had been cleansed. Octreotide accelerated initial gastric emptying (p = 0.05), inhibited small bowel transit (p < 0.01), and reduced ileocolonic bolus transfers (p < 0.05). Colonic transit was unaltered by octreotide; the postprandial colonic tonic response was inhibited (p < 0.05 v placebo), whereas colonic phasic pressure activity was increased by octreotide (p < 0.05 v placebo). These data support the use of octreotide in diarrhoeal states but not in diseases that cause small bowel stasis and bacterial overgrowth. Simultaneous measurements of colonic transit, tone, and phasic contractility are valid in studying the effects of pharmacological changes and may be applicable to the study of the human colon in health and disease.  相似文献   

5.
BACKGROUND: Gut transit measurements are essential for understanding the pathophysiology of many gastrointestinal disorders. The ideal bowel transit test should be easy to perform, widely accessible, reproducible, non-invasive and inexpensive and the risks should be minimal. These requirements prompted us to develop a procedure for simultaneous measurement of gastric emptying, small-bowel transit and colonic transit at one visit. We assessed the influence of gender, body mass index, age, menopause and smoking on gastrointestinal transit in healthy subjects. METHODS: Eighty-three healthy subjects (43 women) were included. Colonic transit was based on 10 radiopaque rings given daily for 6 days with fluoroscopy on day 7. Then, the subjects had a test meal containing 20 radiopaque markers. Using fluoroscopy, gastric emptying and small-bowel transit of the markers were followed until they reached the colon. RESULTS: Gastric emptying, small-bowel transit and colonic transit were significantly slower in female healthy subjects compared to males (2.9 (1.6-4.9) h, median and percentile 10-90, versus 2.4 (0.7-3.7) h, P=0.005; 4.4 (2.1-11.1) h versus 3.2 (1.5-6.0) h, P=0.001; 1.5 (1.0-3.7) days versus 1.3 (0.8-1.9) days P=0.002), respectively. Small-bowel transit was significantly faster in women with overweight and in postmenopausal women compared to lean and premenopausal women, respectively. CONCLUSION: This procedure meets most of the requirements of the ideal bowel transit test and is easily performed at one visit. Small-bowel transit as well as gastric emptying and colonic transit were significantly slower for women.  相似文献   

6.
Profiles for gastric emptying and colonic filling were determined in 20 normal volunteers by means of a gamma camera and dedicated minicomputer after ingestion of a radiolabeled solid meal. These were compared with intraluminal pressure activity, recorded simultaneously from three sites (each separated by 50 cm) in the small intestine by infusion manometry. Recordings were continued for at least 8 h or until all the radioactivity appeared in the colon. Colonic filling was approximately linear, occurring at an average rate of 16% of the meal residues per hour. There were significant inverse correlations (p less than 0.01) between the pressure activity in the proximal jejunum during the first 3 h after ingestion and the times taken for 50% and 80% of the meal residues to enter the colon, and direct correlations between total small intestinal pressure activity and the half-time for gastric emptying. Phase III of the interdigestive migrating motor complex appeared between 3 and 9 h after ingestion (when between 15% and 80% of the meal remained in the small intestine), but did not necessarily migrate to the next recording site until much later. The time of appearance of phase III in the proximal jejunum was directly correlated with the half-time for gastric emptying (p less than 0.05) and with the intraluminal pressure activity recorded at that site during the first 3 h after food ingestion (p less than 0.01). The time at which 80% of the meal residues had entered the colon was significantly shorter in 6 subjects, in whom a postprandial activity front appeared to migrate throughout the small bowel, compared with 13 subjects, in whom this did not occur (5.0 +/- 0.5 h vs. 7.0 +/- 0.4 h, p less than 0.01). These studies have shown that gastrointestinal transit of a solid meal is related to both fed and fasted intraluminal pressure activity in the small intestine.  相似文献   

7.
A method for determining the profiles of gastric emptying, small intestinal residence, and colonic filling of a solid test meal, labelled with 250 microCi 99mTechnetium sulphur colloid has been evaluated in nine healthy volunteers and six patients with a disturbance in bowel habit. Mean small bowel transit time was determined by deconvolving the rate of colonic filling with the rate of gastric emptying. In normal subjects, the stomach appeared to empty exponentially with a half time of 1.2 +/- 0.3 hours (mean +/- SD). Food reached the colon by 2.8 +/- 1.5 hours. The mean small bowel transit time was 4.0 +/- 1.4 hours. In most normal subjects, the colon appeared to fill in a linear fashion with approximately 16% food residues entering every hour, and the profile of colonic filling in normal subjects was similar to the profile of ileal emptying observed after feeding a similar radiolabelled solid meal to 14 patients equipped with terminal ileostomies. There was a highly significant correlation between the onset of breath hydrogen excretion and the appearance of radioactivity over the caecum (r = 0.88, p less than 0.01), though in one third of subjects the increase in caecal radioactivity preceded the rise in breath hydrogen concentration by more than 20 minutes. There was also a highly significant correlation between the mean transit time and values for colonic filling but not values for gastric emptying. Patients with irritable bowel syndrome who had diarrhoea tended towards short small bowel transit and early colonic filling, whereas patients who have constipation tended towards long small bowel transit and delayed colonic filling. This method offers a novel means of assessing small bowel transit time, small bowel residence and the profile of colonic filling in man.  相似文献   

8.
S S Rao  N W Read    C D Holdsworth 《Gut》1987,28(11):1474-1477
The effect of olsalazine on stool output and the transit of a solid radiolabelled meal through the stomach, small intestine and colon was studied in six patients with ulcerative colitis intolerant of sulphasalazine. Olsalazine 250 mg four times daily significantly accelerated gastric emptying (mean +/- SD; 45.3 +/- 24.2 min v 67.3 +/- 33.1 min, p less than 0.05), mouth to caecum transit time (242 +/- 41 min v 325 +/- 33 min, p less than 0.02) and whole gut transit time (60.5 +/- 26 h v 37.8 +/- 17.8 h, p less than 0.05). No significant changes were seen in mean daily stool weight (215 +/- 41 g v 162 +/- 62 g) and mean daily stool frequency (2.2 +/- 0.6 v 2.4 +/- 1.8). None of these patients developed diarrhoea, but acceleration of gastric and intestinal transit may be responsible for the diarrhoea reported in some patients taking this drug.  相似文献   

9.
BACKGROUND: Existing data on gastric emptying and small-intestinal transit rates in portal-hypertensive patients are scarce and contradictory, and so far, the motor function of the colon has not been assessed in these patients. In this study we evaluated the propulsive effect of all main segments of the gastrointestinal tract in patients with well-characterized portal hypertension. METHODS: Eight patients with a postsinusoidal hepatic pressure gradient of at least 13 mmHg and eight age- and sex-matched healthy controls participated in the study. Gastric emptying, small-intestinal transit, and colonic transit rates were evaluated in all subjects by means of a gamma camera technique. The technique was also used to measure the frequency of antral contractions. RESULTS: No difference was observed in gastric mean emptying time or small-intestinal mean transit time of liquid and solid markers between patients and controls. After 24 h, however, the geometric center of the liquid marker had a more caudal localization in the colon of the patient group than in the controls (P = 0.04); that is, the patients had a faster colonic transit. No difference was found in the frequency of antral contractions 45 min after the test meal between patients and controls. CONCLUSIONS: These data suggest that the colonic transit is often accelerated in patients with portal hypertension, whereas the motor function of the stomach and the small intestine is unaffected.  相似文献   

10.
Background: Existing data on gastric emptying and small-intestinal transit rates in portal-hypertensive patients are scarce and contradictory, and so far, the motor function of the colon has not been assessed in these patients. In this study we evaluated the propulsive effect of all main segments of the gastrointestinal tract in patients with well-characterized portal hypertension. Methods: Eight patients with a postsinusoidal hepatic pressure gradient of at least 13 mmHg and eight age- and sex-matched healthy controls participated in the study. Gastric emptying, small-intestinal transit, and colonic transit rates were evaluated in all subjects by means of a gamma camera technique. The technique was also used to measure the frequency of antral contractions. Results: No difference was observed in gastric mean emptying time or small-intestinal mean transit time of liquid and solid markers between patients and controls. After 24 h, however, the geometric center of the liquid marker had a more caudal localization in the colon of the patient group than in the controls (P = 0.04); that is, the patients had a faster colonic transit. No difference was found in the frequency of antral contractions 45 min after the test meal between patients and controls. Conclusions: These data suggest that the colonic transit is often accelerated in patients with portal hypertension, whereas the motor function of the stomach and the small intestine is unaffected.  相似文献   

11.
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.  相似文献   

12.
J Cammack  N W Read  P A Cann  B Greenwood    A M Holgate 《Gut》1982,23(11):957-961
The effect of intermittent moderate exercise on the passage of a solid meal, labelled with radioactive Technetium sulphur colloid, through the stomach and small intestine was investigated by paired studies on seven healthy volunteers. Measurements of gastric radioactivity and breath hydrogen exertion were recorded every 10 minutes while subjects exercised in a controlled manner while seated on a bicycle ergometer. These were compared with values obtained during a separate experiment while the same subjects sat upright in a chair. Exercise significantly accelerated gastric emptying (control t 1/2 = 1.5 +/- 0.1 h; exercise t 1/2 = 1.2 +/- 0.1 h; p less than 0.02) but had no significant effect on small bowel transit time.  相似文献   

13.
B Werth  B Meyer-Wyss  G A Spinas  J Drewe    C Beglinger 《Gut》1992,33(9):1199-1203
Twenty six patients with insulin dependent diabetes mellitus underwent a gastric emptying test, a gall bladder contraction test, an orocaecal transit study, and a colon transit test. Eleven patients had signs of cardiovascular autonomic neuropathy, 15 patients were without signs of cardiovascular autonomic neuropathy. Mean gastric clearance of radioopaque markers ingested with a meal averaged 29.5 (2.3) markers per six hours in subjects without cardiovascular autonomic neuropathy compared with 17.8 (2.3) markers per six hours in patients with cardiovascular autonomic neuropathy (p < 0.02). Gall bladder emptying in response to graded CCK8 stimulation was impaired in five of 11 patients with cardiovascular autonomic neuropathy, whereas it was normal in the patients without cardiovascular autonomic neuropathy (p < 0.01). Oral caecal transit times were not significantly different in the two patient groups, whereas colonic transit was slower in the patients with cardiovascular autonomic neuropathy compared with the group without cardiovascular autonomic neuropathy (p < 0.02). There was no correlation between disturbed gastric clearance, impaired gall bladder contraction, and prolonged colonic transit time in the patients with cardiovascular autonomic neuropathy nor was there a correlation between any disturbed motor function and age or duration of diabetes. It is concluded that autonomic neuropathy can affect motor functions throughout the gastro-intestinal tract. Any disturbed motor function in the gut could therefore be one of the numerous expressions of diabetic neuropathy affecting the cardiovascular, the endocrine or the gastrointestinal system.  相似文献   

14.
Bouras EP  Camilleri M  Burton DD  McKinzie S 《Gut》1999,44(5):682-686
BACKGROUND: Prucalopride (R093877) is a selective and specific 5HT4 agonist, the first of a new chemical class of benzofurans, with gastrointestinal prokinetic activities in vitro. AIMS: To evaluate the effects of prucalopride on gastrointestinal and colonic transit. METHODS: A validated scintigraphic technique was used to measure gastrointestinal and colonic transit over 48 hours in 50 healthy volunteers. For seven days, each subject received a daily dose of 0. 5, 1, 2, or 4 mg prucalopride, or placebo in a double blind, randomised fashion. The transit test was performed over the last 48 hours. RESULTS: There were significant accelerations of overall colonic transit at 4, 8, 24, and 48 hours (p<0.05) and proximal colonic emptying t1/2 (p<0.05). The 0.5, 2, and 4 mg doses of prucalopride were almost equally effective and accelerated colonic transit compared with placebo. Prucalopride did not significantly alter gastric emptying (p>0.5) or small bowel transit (overall p=0. 12). The medication appeared to be well tolerated during the seven day treatment of healthy subjects. CONCLUSION: Prucalopride accelerates colonic transit, partly by stimulating proximal colonic emptying, but does not alter gastric or small bowel transit in healthy human subjects. Prucalopride deserves further study in patients with constipation.  相似文献   

15.
The effect of gastric emptying of two doses (35 and 70 micrograms) of enprostil given orally was evaluated in eight patients with endoscopically confirmed duodenal ulcer. Gastric emptying of a radiolabelled solid meal was assessed with the use of a gamma camera. Enprostil dose-dependently accelerated gastric emptying of solids; the gastric emptying index, Ix, increased from 1.62 +/- 0.38 min-1.10(-2) after placebo to 2.77 +/- 0.56 min-1.10(-2) after 35 micrograms enprostil (p less than 0.05 versus placebo) and to 3.65 +/- 0.64 min-1.10(-2) after 70 micrograms enprostil (p less than 0.005 versus placebo). The fraction of the radiolabelled food retained in the stomach at the end of the gastric emptying examination (that is, after 90 min) amounted to 50.5 +/- 6.9% after placebo, 35.2 +/- 7.4% after 35 micrograms enprostil, and 24.1 +/- 8.4% after 70 micrograms enprostil. It is concluded that enprostil elicits a significant speeding up of solid-phase gastric emptying in duodenal ulcer patients.  相似文献   

16.
OBJECTIVE: To further delineate motor activity of the upper gastrointestinal tract in patients with slow-transit constipation. DESIGN: A prospective study comparing healthy volunteers with patients with a clinical diagnosis of slow-transit constipation. METHODS: Eighteen patients with clinical diagnosis of slow-transit constipation and 10 healthy controls were included in the study. Fasting antroduodenal motility was measured by perfusion manometry for at least one complete cycle of the migrating motor complex or a maximum of 300 min. Oesophageal manometry, gastric emptying and orocaecal transit time measurements were also performed. RESULTS: At least one complete cycle of the migrating motor complex was observed in all controls, but in only nine patients (P < 0.01 versus control). The migrating motor complex cycle was incomplete (n = 5) or phase 3 activity was absent (n = 4) in the other patients. The incidence of clustered contractions was significantly increased in slow-transit constipation (P = 0.05 versus controls). The area under the contraction curve during late phase 2 (1509+/-296 mmHg x s) in patients with a complete cycle was significantly smaller than that in controls (2997+/-614 mmHg x s; P = 0.05). Orocaecal transit time was not significantly different among patients and controls, but oesophageal motility was abnormal in five of 18 patients and gastric emptying was abnormal in eight of 15 patients. CONCLUSION: Abnormalities of upper gut motility occur frequently in patients with slow-transit constipation. Interdigestive antroduodenal motility is characterized by (i) absence or prolonged duration of the migrating motor complex, (ii) an increased number of clustered contractions, or (iii) a decreased motility during late phase 2 of the migrating motor complex.  相似文献   

17.
A McIntyre  R M Vincent  A C Perkins    R C Spiller 《Gut》1997,40(2):223-227
BACKGROUND: Coarse bran is known to accelerate transit through the whole gut and to increase stool weight. This effect is much reduced by grinding the bran, suggesting that particle size influences gut motor patterns. AIMS: To compare the effect of 15 g coarse bran with 15 g inert plastic particles and 7 g of ispaghula on the gastric emptying and small bowel transit of a rice pudding test meal. SUBJECTS: 13 healthy volunteers. METHODS: Transit of 99mTc labelled rice studied by gamma-scintigraphy measuring gastric emptying and colonic arrival over 10 hours. Small bowel transit was estimated from the difference between time to 50% gastric emptying and 50% colonic arrival. RESULTS: Bran delayed gastric emptying by 22 (SEM 8) minutes compared with control values of 88 (SEM 6) minutes p < 0.05. Ispaghula and plastic particles had no significant effect. Small bowel transit was accelerated compared with control values of 322 (SEM 29) minutes, decreasing by 95 (29) minutes and 62 (22) minutes after bran and plastic particles respectively. Ispaghula again showed no significant effect. CONCLUSION: Coarse bran delays gastric emptying and accelerates small bowel transit. The marked acceleration of small bowel transit also seen with inert plastic particles may be due to increased upper gut secretions after stimulation of enteric nerves.  相似文献   

18.
Objectives: Previous studies showed increased plasma motilin and substance P concentrations and accelerated motor function in the small bowel and colon in patients with carcinoid diarrhea. Octreotide is beneficial in patients with carcinoid syndrome. Our hypothesis was that octreotide inhibits accelerated motility and gut neuropeptides in carcinoid syndrome. Methods : In 12 patients with metastatic carcinoid syndrome, we investigated the effect of octreotide 50 μg s.c. t.i.d (n = 6) or placebo (n = 6) on postprandial symptoms, GI transit, colonic motility, and circulating levels of selected circulating peptides and amines. Results : Octreotide reduced postprandial flushing ( p = 0.03) but not pain. Octreotide significantly retarded overall colonic transit and proximal colonic emptying ( p < 0.05); it tended to prolong small bowel transit time ( p = 0.13) and to reduce postprandial colonic tone ( p = 0.08) compared with placebo. Octreotide also reduced circulating levels of peptide YY, neurotensin, vasoactive intestinal polypeptide, and substance P but had no effect on plasma motilin, neuropeptide Y, calcitonin gene-related peptide, or histamine after meal ingestion. Conclusion : Octreotide ameliorates gut motor dysfunctions that characterize carcinoid diarrhea; the potential role of specific antagonism of serotonin, substance P, and vasoactive intestinal polypeptide alone or in combination with agents that inhibit their release in carcinoid diarrhea deserves further study.  相似文献   

19.
A double-blind cross-over trial of oral cisapride 10 mg before meals and placebo was performed to determine its effects on colonic transit in patients with severe idiopathic constipation. Nine patients with less than 3 spontaneous bowel movements/wk were studied. After passing a tube to the cecum, 50 muCi of 111In-DTPA were instilled into the cecum and followed for 48 h using colonic transit scintigraphy. In the group as a whole, cisapride had little effect on transit. The patients were then divided into two groups based on transit: functional rectosigmoid obstruction (FRSO) and colonic inertia (CI). In the CI group, cisapride accelerated the half emptying time of the cecum and ascending colon from 2.50 to 1.21 h (p less than 0.05). The progression of the geometric center was also faster after cisapride in CI. In FRSO, the geometric center was unchanged by cisapride except at 48 h. Cisapride thus has a prokinetic effect on colonic transit in patients with severe idiopathic constipation, colonic inertia subtype. It may be a useful agent in the treatment of this group of patients.  相似文献   

20.
J D O''Brien  D G Thompson  W R Burnham  J Holly    E Walker 《Gut》1987,28(8):960-969
Two well established experimental stressors, hand immersion in cold water, and mental stimulation with dichotomous listening, were applied to 37 normal subjects after the ingestion of a standard meal. Orocaecal transit was measured by serial exhaled breath hydrogen sampling. Cold water significantly delayed transit compared with warm water control (warm water 71.8 +/- 3.6 mins v cold water 93.2 +/- 5.7 mins p less than 0.01), with significant rises in blood pressure pulse rate perceived discomfort and plasma catecholamines. In contrast mental stimulation was unaccompanied by any change in transit (control; 67.4 +/- 4.7 v test 64.3 +/- 5.3 mins p greater than 0.1) despite a significant rise in pulse rate, skin conductance and plasma catecholamines. Repeated cold water immersion studies in eight individuals produced consistent orocaecal transit and autonomic responses, whereas mental stimulation showed reduced autonomic responses on repeat testing, suggesting that tolerance to the stimulus had occurred. The results of these studies show stimulus specific gastrointestinal response patterns to autonomic stimuli, and appear to have important implications for the design of future studies of human gastrointestinal autonomic physiology and for the investigation of patients with stress related gut dysfunction.  相似文献   

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