Biomedical subjects

M Samsom

Publications and source records attributed to M Samsom.

At least 19 recordsLinked to original sources

PubMed2006

The 5-HT4 antagonist R216073 does not affect gastric motor and sensory function in patients with functional dyspepsia.

BACKGROUND: Serotonin and the 5-HT4 receptor play an important role in gastrointestinal motor and sensory functions. While 5-HT4 agonists are known for their prokinetics properties, the effect of 5-HT4 antagonists on upper gastrointestinal functions is largely unknown. AIM: To assess the effect of a 5-HT4 receptor antagonist (R216073) on gastric relaxation and visceral sensitivity in patients with functional dyspepsia. Secondly, the influence of a functional polymorphism in the gene encoding the serotonin transport protein on drug response was determined. METHODS: A double-blind, randomized, placebo-controlled, two-period crossover study was performed in 20 functional dyspepsia patients. The effect of a single dose of 2,000 mg R216073 on gastric relaxation and sensitivity was tested using three-dimensional ultrasonography and a nutrient drinktest. RESULTS: R216073 did not affect partial gastric volumes or upper abdominal sensations scored during three-dimensional ultrasonography (P > 0.05). The maximum tolerated volume or upper abdominal sensations induced by the drinktest were not affected by R216073 (P > 0.05). The serotonin transport protein promoter polymorphism was not associated with any of the end-points of the study. CONCLUSIONS: A single dose of R216073 had no effect on fundic relaxation, drinking capacity, or upper abdominal symptoms in patients with functional dyspepsia.

Adult↗

PubMed2006

Endoscopic gastroplication for the treatment of gastro-oesophageal reflux disease: a randomised, sham-controlled trial.

BACKGROUND: Endoscopic treatment for gastro-oesophageal reflux disease (GORD) is rapidly emerging, but there is a great need for randomised controlled trials to evaluate the efficacy. DESIGN AND SETTING: A single-centre, double-blind, randomised, sham-controlled trial of endoscopic gastroplication by the Endocinch suturing system. PATIENTS AND INTERVENTIONS: 60 patients with GORD were randomly assigned to three endoscopic gastroplications (n = 20), a sham procedure (n = 20) or observation (n = 20). The research nurse and patients in the active and sham groups were blinded to the procedure assignment. After 3 months, open-label active treatment was offered to all patients. OUTCOME MEASURES: The primary outcome measures were proton pump inhibitor (PPI) use and GORD symptoms, and secondary measures were quality of life, 24-h oesophageal acid exposure, oesophageal manometry and adverse events. Follow-up assessments were performed at 3, 6 and 12 months. RESULTS: At 3 months, the percentage of patients who had reduced drug use by > or =50% was greater in the active treatment group (65%) than in the sham (25%) or observation groups (0%) (p<0.02). Symptoms (heartburn and to a lesser extent regurgitation) improved more in the active group than in the sham group. Three Short Form-20 quality of life subscales (role function, general health and bodily pain perception) improved in the active group versus sham. Oesophageal acid exposure was modestly decreased after active treatment (p<0.02), but not significantly greater than after the sham procedure (p = 0.61). The active treatment effects on PPI use, symptoms and quality of life persisted after 6 and 12 months of open-label follow-up (n = 41), but 29% of patients were retreated in this period. No serious adverse events occurred. CONCLUSIONS: Endoscopic gastroplication, using the Endocinch device, reduced acid-inhibitory drug use, improved GORD symptoms and improved the quality of life at 3 months compared with a sham procedure. The effects persisted up to 12 months. However, the reduction in oesophageal acid exposure was not greater after endoscopic treatment than after a sham procedure.

Antacids↗

PubMed2006

Fundal dysaccommodation in functional dyspepsia: head-to-head comparison between the barostat and three-dimensional ultrasonographic technique.

BACKGROUND: Recently, non-invasive techniques such as 3 dimensional ultrasonography (3DUS) have been developed to assess gastric wall characteristics and to investigate their relationship with upper gastrointestinal sensations. To date, no head-to-head comparison has been carried out between the barostat and the 3DUS technique. AIM: To compare barostat and 3DUS and to investigate the relationship between gastric volumes and sensations in patients with functional dyspepsia and in healthy subjects. PATIENTS AND METHODS: Gastric accommodation was studied in 15 patients with functional dyspepsia and in 15 healthy subjects after ingestion of a liquid nutrient (300 kcal) using barostat and 3DUS in random order for 60 min. Proximal gastric relaxation was measured using barostat and gastric volume using 3DUS. Change in gastric volume, acquired by 3DUS, was expressed as total gastric volume/proximal volume ratio (TGV/PV) and compared with changes in barostat volume (fundal accommodation). RESULTS: Patients with functional dyspepsia showed a smaller change in proximal gastric volume than healthy subjects using barostat (mean (SD) 82 (61) v 205 (79) ml, p<0.01) and 3DUS (118 (41) v 199 (39) ml, p<0.01). Dysaccommodation of the proximal stomach was observed in 7 of 15 (46%) patients using the barostat technique. 10 of 15 (67%) patients were found to have an abnormal change in proximal gastric volume using TGV/PV ratio. At 5 min postprandially, fullness was related to the change in distal gastric volume (r = 0.51, p = 0.006) in the 3DUS study, whereas no relationship was observed in the barostat study. CONCLUSION: 3DUS is a feasible non-invasive technique to measure gastric volumes and shows a distinct overlap with barostat data in healthy subjects and patients with functional dyspepsia. Fullness relates to distal gastric volumes when assessed by non-invasive 3DUS.

Adaptation, Physiological↗

PubMed2006

Assessment of oesophageal emptying in achalasia patients by intraluminal impedance monitoring.

Oesophageal emptying can be assessed by radiographic and scintigraphic tests with radiation exposure or by multichannel intraluminal impedance monitoring (MII). The aim of this study was to evaluate the applicability of MII for the assessment of oesophageal emptying in achalasia patients. In 10 achalasia patients, impedance tracings were scored independently by three observers after ingestion of a 100-mL barium bolus. Bolus clearance time (BCT) and height of barium column were scored using fluoroscopic images acquired at 20-s intervals. All patients showed a low baseline impedance level in the distal oesophagus. Air trapping in the proximal oesophagus was detected in nine patients. BCT on MII was similar to that on fluoroscopy in 40-70% of the patients. Correlations between height of barium on fluoroscopy and fluid level on MII were poor to moderate at different time intervals. Concordance (Kendall's coefficient) between the three observers for assessment of fluid level on MII was 0.31 (P = 0.04) at 1 and 5 min, 0.26 (P = 0.08) at 10 and 0.44 (P = 0.01) at 15 min. We conclude that in achalasia patients, low baseline impedance levels and air entrapment in the proximal oesophagus limit the value of intraluminal impedance monitoring as a test of oesophageal emptying.

Adult↗

PubMed2006

The gastro-oesophageal common cavity revisited.

The manometric common cavity phenomenon has been used as indicator of gastro-oesophageal reflux of liquid or gaseous substances. Using combined pH and impedance recording as reference standard the value of a common cavity as indicator of gastro-oesophageal reflux was tested. Ten healthy male subjects underwent combined stationary pressure, pH and impedance recording for 4.5 h. After 1.15 h of recording, a reflux-eliciting meal was consumed. The chi-squared and Kolmogorov-Smirnov tests were used for the statistical analysis. A common cavity was found in 95 (43%) of the 223 reflux events detected by impedance, while seven common cavities were unrelated to a reflux episode. In 54% of the reflux events detected by impedance without a common cavity, a possible common cavity was obscured by either contractile activity or artefacts of various origin. The types of reflux associated with a common cavity (liquid 60%, mixed 31%, gas 9%) and without a common cavity (liquid 59%, mixed 29%, gas 12%) did not differ, or did the acidity of the reflux episodes (with common cavity: acid 67%; without common cavity: acid 58%). The common cavity is a specific but not a sensitive marker of gastro-oesophageal reflux. Furthermore, common cavities are not specific for a particular type of reflux.

Adult↗

PubMed2005

Relationships between gastric accommodation and gastrointestinal sensations in healthy volunteers. A study using the barostat technique and two- and three-dimensional ultrasonography.

The origin of postprandial gastrointestinal sensations and their relation to gastric accommodation remain unclear. Our aim was to investigate the relation between antral and fundal accommodation and sensations. (A) In eight healthy volunteers fundus accommodation was measured using a barostat after a 200-ml (300-kcal) liquid nutrient. Antral area (AA) was measured using ultrasound. Data on bag volumes, AA, and sensations were assessed. (B) In another eight healthy volunteers gastric volume was measured after a 500-ml (300-kcal) liquid nutrient using 2-D/3-D ultrasound. Sensations were scored using VAS. Distal and proximal volumes were calculated from 3-D datasets. (A) Fullness was correlated with AA (r = 0.48, P = 0.002). Fullness and bag volume were not correlated. (B) Fullness was correlated with AA (r = 0.77, P < 0.001) and distal volume (r = 0.75, P < 0.001). Proximal volume was not correlated with fullness (r = 0.10, P = NS). We conclude that fullness is related to antral volume and area rather than proximal volume. The gastric antrum may play a key role in normal appetite regulation.

Adolescent↗

PubMed2005

Relationship between the mechanism of gastro-oesophageal reflux and oesophageal acid exposure in patients with reflux disease.

This study investigated the relationship between the oesophageal acid exposure time and the underlying manometric motor events in patients with gastro-oesophageal reflux disease (GORD). In 31 patients, 3-hour oesophageal motility and pH were measured after a test meal. Ten patients underwent 24-hour ambulatory manometry and pH recording. In the 3-hour postprandial study, of 367 reflux episodes 79% was associated with a transient lower oesophageal sphincter relaxation (TLOSR), 14% with absent basal lower oesophageal sphincter (LOS) pressure and the remaining 7% with other mechanisms, representing 62, 28 and 10% of the acid exposure time, respectively. Acid reflux duration per motor mechanism was longer for absent basal LOS pressure than for TLOSR (189 +/- 23 s and 41 +/- 5 s, respectively, P < 0.001). In the 24-hour ambulatory study, the contribution of TLOSRs to reflux frequency vs acid exposure time were 65 vs 54% interprandially and 74 vs 53% after the meal. During the night, absence of basal LOS pressure accounted for 36% of reflux events representing 71% of acid exposure time. In conclusion, the duration of oesophageal acid exposure following a TLOSR is shorter than reflux during absent basal LOS pressure. TLOSRs are, the major contributor to oesophageal acid exposure during the day. At night, however, reflux during absent basal LOS pressure is the major contributor to acid exposure.

Adult↗

PubMed2005

Impaired bolus transit across the esophagogastric junction in postfundoplication dysphagia.

OBJECTIVES: This study assessed the effect of fundoplication on liquid and solid bolus transit across the esophagogastric junction (EGJ) in relation to EGJ dynamics and dysphagia. METHODS: Twelve patients with gastro-esophageal reflux disease (GERD) were studied before and after fundoplication. Concurrent high-resolution EGJ manometry and fluoroscopy were performed whilst swallowing liquid barium and a solid bolus. The EGJ transit time, EGJ opening duration, transit efficacy, and EGJ relaxation were measured. During the test symptoms of dysphagia were scored using a visual analog scale. RESULTS: The minimal opening aperture at fluoroscopy was located at the manometric EGJ in all subjects. Fundoplication markedly reduced the EGJ opening diameter from 1.0 +/- 0.1 to 0.6 +/- 0.1 cm (p < 0.01) and rendered deglutative EGJ relaxation incomplete. After fundoplication, a higher intrabolus pressure was found (p < 0.05) associated with a reduced axial bolus length (p < 0.001). EGJ transit time increased from 6.9 +/- 0.9 to 9.8 +/- 1.0 s for liquids (p < 0.01) and from 2.8 +/- 0.5 to 5.8 +/- 0.8 s (p < 0.01) for solids after fundoplication. No relation between EGJ transit and dysphagia scores was observed before fundoplication. In contrast, EGJ transit time significantly correlated with dysphagia scores both during liquid (r = 0.84; p < 0.01) and solid (r = 0.69; p < 0.05) bolus transit following fundoplication. CONCLUSIONS: Fundoplication patients exhibit a restricted hiatal opening and an incomplete deglutative EGJ relaxation. To facilitate EGJ transit despite these altered EGJ dynamics a higher intrabolus pressure is created by augmented bolus compression. Fundoplication increases EGJ transit time, the degree of which is associated with postoperative dysphagia.

Adult↗

PubMed2004

Long-term effect of fundoplication on motility of the oesophagus and oesophagogastric junction.

BACKGROUND: This study assessed the long-term effect of Nissen fundoplication on oesophageal and oesophagogastric junction (OGJ) motility. METHODS: Symptoms were scored and oesophageal manometry performed in 34 consecutive patients with chronic gastro-oesophageal reflux disease, before, 3 months after and 2 years after surgery. RESULTS: Distal peristaltic amplitude increased from a median of 57 (95 per cent confidence interval (c.i.) 18 to 107) mmHg to 86 (95 per cent c.i. 54 to 208) mmHg (P < 0.001) at 3 months and 92 (45 to 210) mmHg (P < 0.001) at 2 years. In four patients the amplitude increased to more than 180 mmHg and three of these patients reported odynophagia. After surgery, a linear relationship was observed between the peristaltic amplitude and nadir OGJ relaxation pressure at 3 months (r(s) = 0.68, P < 0.001) and 2 years (r(s) = 0.64, P < 0.001). A significant correlation was also found between amplitude and both basal OGJ pressure and intrabolus pressure at 3 months (r(s) = 0.58, P < 0.001 and r(s) = 0.63, P < 0.001 respectively) and 2 years (r(s) = 0.71, P < 0.001 and r(s) = 0.49, P = 0.024). There was a relationship between peristaltic amplitude and the odynophagia score at 2 years (r(s) = 0.60, P = 0.017). CONCLUSION: Within 3 months of fundoplication the amplitude of oesophageal peristalsis increased substantially, leading to a nutcracker oesophagus and odynophagia in a subgroup of patients. These phenomena did not appear to progress with time.

Deglutition Disorders↗

PubMed2004

Potential of genetic translational research in gastroenterology.

The concept that genetic variation underlies inter-individual differences in drug response and contributes to the risk of developing common, complex disorders is expanding rapidly. Consequently the interest in genetic translational research has increased. Polymorphic DNA markers, either microsatellites or single nucleotide polymorphisms (SNPs), are used to assess genetic identities and track genetic differences between individuals. Given their abundance and stability, SNPs hold great promise as markers for mapping disease susceptibility loci for common, complex disorders by association studies. For this purpose the development of inexpensive, accurate, high-throughput methods for scoring large numbers of SNPs from hundreds of patients and controls is critical. Furthermore, gene expression profiling using DNA microarrays is likely to become a useful diagnostic tool enabling classification of disease phenotype based on molecular basis of disease pathogenesis, revealing information that cannot be obtained by histological assessment. Moreover, identification of differentially expressed genes in affected versus control tissue or over time in affected tissue will lead to better understanding of the mechanisms underlying disease and ultimately to the development of more effective drug therapies. To illustrate the potential of genetic translational research, several examples in the field of gastroenterology are described.

Gastrointestinal Diseases↗

PubMed2004

Relationship between partial gastric volumes and dyspeptic symptoms in fundoplication patients: a 3D ultrasonographic study.

OBJECTIVES: Impaired gastric accommodation may induce dyspeptic symptoms in postfundoplication patients. Our aim was to assess the effect of a meal on total and partial gastric volumes in relation to dyspeptic symptoms in both dyspeptic and nondyspeptic fundoplication patients using three-dimensional (3D) ultrasonography. METHODS: Eighteen postfundoplication patients of whom eight with and ten without dyspeptic symptoms and eighteen controls were studied. Three-dimensional ultrasonographic images of the stomach were acquired and symptoms were scored while fasting and at 5, 15, 30, 45, and 60 min after ingesting of a 500-ml liquid meal. From the 3D ultrasonographic images of the stomach the total, proximal, and distal gastric volumes were computed. RESULTS: Dyspeptic and nondyspeptic fundoplication patients exhibited similar total gastric volumes at 5 min postprandially compared to controls, whereas smaller total gastric volumes were observed from 15 to 60 min postprandially (p = 0.007 and p < 0.001, respectively). Postprandial proximal/total gastric volume ratios were markedly reduced in both dyspeptic (0.39 +/- 0.016; p < 0.05) and nondyspeptic (0.38 +/- 0.016; p < 0.01) fundoplication patients compared to controls (0.47 +/- 0.008). In contrast, distal/total gastric volume ratios were larger in dyspeptic fundoplication patients (0.14 +/- 0.008) compared to both nondyspeptic fundoplication patients (0.11 +/- 0.007); p < 0.05) and controls (0.07 +/- 0.003); p < 0.001). Dyspeptic fundoplication patients had a higher postprandial score for fullness, nausea, and pain than nondyspeptic patients (p < 0.05) and controls (p < 0.05). Meal-induced distal gastric volume increase correlated significantly with the increase in fullness (r = 0.68; p < 0.01). CONCLUSIONS: After a liquid meal, fundoplication patients exhibit a larger volume of the distal stomach compared with controls. Distal stomach volume was more pronounced in dyspeptic fundoplication patients and related with the increase in postprandial fullness sensations.

Adult↗

PubMed2004

Colorectal visceral perception in diverticular disease.

BACKGROUND AND AIMS: The pathogenesis of asymptomatic diverticular disease (ADD) and symptomatic uncomplicated diverticular disease (SUDD) has not been elucidated. The aim of our study was to assess whether altered visceral perception or abnormal compliance of the colorectal wall play a role in these clinical entities. METHODS: Ten ADD patients, 11 SUDD patients, and nine healthy controls were studied. Using a dual barostat device, sensations were scored and compliance curves obtained using stepwise intermittent isobaric distensions of the rectum and sigmoid, before and after a liquid meal. In addition, the colonic response to eating was assessed by monitoring the volumes of both barostat bags at operating pressure before and after the meal. RESULTS: In the rectum, perception was increased in the SUDD group compared with controls (p = 0.010) and the ADD group (p = 0.030). Rectal compliance curves were not different between the groups. In the sigmoid colon, perception in the pre- and postprandial periods was increased in SUDD compared with controls (p = 0.018) but not when compared with ADD. Sigmoid volume-pressure curves had comparable slopes (compliance) in all groups but were shifted downwards in SUDD compared with ADD in the preprandial period (p = 0.026). The colonic response to eating (decrease in intrabag volume) was similar in all three groups, both in the rectum and sigmoid. CONCLUSION: Symptomatic but not asymptomatic uncomplicated diverticular disease is associated with heightened perception of distension, not only in the diverticula bearing sigmoid, but also in the unaffected rectum. This hyperperception is not due to altered wall compliance.

Adult↗

PubMed2003

Abnormalities of left colonic motility in ambulant nonconstipated patients with irritable bowel syndrome.

Our objective was to evaluate left colonic motility patterns recorded under physiological conditions during 24 hr in fully ambulant nonconstipated IBS patients compared to healthy controls. A 42-hr manometry of the left colon was performed in 11 nonconstipated IBS patients and 10 age- and sex-matched healthy volunteers. On day 1, a 6-channel, 10-cm interval, solid-state catheter was positioned. Frequency, amplitude, and motility index (MI) of segmenting pressure waves in the descending and sigmoid colon were calculated during the 24-hr study period on day 2. High-amplitude propagated contractions (HAPCs) were identified visually and their characteristics were calculated. In IBS patients a higher frequency of segmenting pressure waves was observed in the sigmoid colon compared to the descending colon (P = 0.006). In contrast, no regional differences were observed in controls. Awakening (P = 0.048) as well as having a meal (P = 0.024) was associated with a smaller increase of contraction frequency in the descending colon of IBS patients compared to controls. HAPCs occurred more frequently in IBS patients than in controls (P = 0.035). HAPCs in IBS patients reached a more distal colonic level and occurred more frequently in clusters. Defecation in IBS patients, but not in controls was always preceded by a cluster of HAPCs. In conclusion, left colonic segmenting pressure waves and HAPC characteristics are altered in nonconstipated IBS patients.

Adult↗

PubMed2003

Effects of a meal and bisacodyl on colonic motility in healthy volunteers and patients with slow-transit constipation.

In the present study, the gastrocolonic response after ingestion of a standardized liquid meal and the response to a local chemical stimulus were investigated in 10 healthy volunteers and 10 patients with slow-transit constipation (as determined by marker studies). Colonic pressures were recorded while fasting, after ingestion of a standardized meal and after intracolonic bisacodyl infusion, using a 12-channel water-perfused catheter. Pressure waves propagating over at least 20 cm (HAPPW) were identified visually and automated analysis was carried out on remaining segmental motility. Increases of motility after a meal and bisacodyl were seen in healthy subjects, whereas patients did not show these responses. The time until occurrence of the first HAPPW after bisacodyl infusion tended to be prolonged (4.3 +/- 1.4 vs 36.1 +/- 15.3; P = 0.053) and the number of HAPPWs in the first 30 min. after infusion was lower compared to healthy subjects (2.1 +/- 0.2 vs 5.4 +/- 0.3; P < 0.01). The percentage of HAPPWs that were experienced as urge or cramp was significantly lower in constipated patients (53 +/- 3% vs 95 +/- 1%; P < 0.005). In conclusion, this study shows that in patients with slow-transit constipation, the colonic motor response to a meal and to bisacodyl, as well as the perception of bisacodyl-induced propagated pressure waves is decreased.

Adult↗

PubMed2003

Association between pain episodes and high amplitude propagated pressure waves in patients with irritable bowel syndrome.

OBJECTIVES: In the pathogenesis of irritable bowel syndrome (IBS), both increased visceral sensitivity and altered colonic motility seem to play a role. The aim of this study was to quantify the temporal relationship between pain episodes and the occurrence of high amplitude propagated pressure waves (HAPPWs). METHODS: A total of 11 IBS patients with the nonconstipation predominant pattern of IBS and 10 sex- and age-matched healthy volunteers were studied. On day 1, a solid state manometric catheter was positioned in the left colon and connected to a data logger. The subjects then went home. Thereafter they pressed a button on the data logger at the beginning and end of each pain episode. The 24-h manometric signal recorded on day 2 was divided into consecutive 5-min periods. These periods were evaluated for the occurrence of pain and HAPPWs. Fisher's exact test was applied to calculate the probability that HAPPWs and pain episodes were unrelated. The symptom association probability (SAP) was calculated as (1.0 - P) x 100%. A SAP of >95% was considered to indicate that the observed association did not occur by chance. RESULTS: In four of seven patients with pain on day 2, the SAP was >95%. HAPPWs that were related to pain originated at a more proximal level (p = 0.026) and occurred earlier (p = 0.007) than HAPPWs that were not related to pain. The duration of a pain period was correlated with the number of pain-related HAPPWs in that period (r = 0.906, p = 0.013). Two of the 10 healthy subjects experienced pain, and these pain episodes were not associated with HAPPWs. CONCLUSIONS: Using objective analysis techniques, an association between pain episodes and HAPPWs was found in nonconstipated IBS patients with pain. HAPPWs that are associated with pain are only slightly different from HAPPWs not associated with pain.

Adult↗

PubMed2003

Prevalence of delayed gastric emptying in diabetic patients and relationship to dyspeptic symptoms: a prospective study in unselected diabetic patients.

OBJECTIVE: Data on the prevalence of abnormal gastric emptying in diabetic patients are still lacking. The relation between gastric emptying and dyspeptic symptoms assessed during gastric emptying measurement has not yet been investigated. The aim was to investigate the prevalence of delayed gastric emptying in a large cohort of unselected diabetic patients and to investigate the relation between gastric emptying and gastrointestinal sensations experienced in the 2 weeks before and during the test meal, prospectively. RESEARCH DESIGN AND METHODS: Gastric emptying was evaluated in 186 patients (106 with type 1 diabetes, mean duration of diabetes 11.6 +/- 11.3 years) using 100 mg (13)C-enriched octanoic acid added to a solid meal. RESULTS: Gastric emptying was significantly slower in the diabetic subjects than in the healthy volunteers (T(50): 99.5 +/- 35.4 vs. 76.8 +/- 21.4 min, P < 0.003; Ret(120 min): 30.6 +/- 17.2 vs. 20.4 +/- 9.7%, P < 0.006). Delayed gastric emptying was observed in 51 (28%) diabetic subjects. The sensations experienced in the 2 weeks before the test were weakly correlated with the sensation scored during the gastric emptying test. Sensations assessed during the gastric emptying test did predict gastric emptying to some extent (r = 0.46, P < 0.0001), whereas sensations experienced in the previous 2 weeks did not. CONCLUSIONS: This prospective study shows that delayed gastric emptying can be observed in 28% of unselected patients with diabetes. Upper gastrointestinal sensations scored during the gastric emptying tests do predict the rate of gastric emptying to some extent and sensation experienced during daily life does not.

Adult↗

PubMed2002

[Irritable bowel syndrome: pathophysiology and (future) treatment options].

Abnormalities of intestinal motility, altered visceral perception and psychological influences are the most important factors in the pathogenesis of irritable bowel syndrome. Current pharmacological treatment options are limited and lack specificity. In the future, it is likely that a number of therapeutic agents with stronger spasmolytic effects (selective muscarinic receptor antagonists), more specific colokinetic properties (5-hydroxytryptamine (5HT)4 agonists) and a positive influence on visceral perception (serotonin (5HT3) receptor antagonists, kappa-agonists) will become available.

Analgesics, Non-Narcotic↗

PubMed2002

The effects of the specific 5HT(4) receptor agonist, prucalopride, on colonic motility in healthy volunteers.

BACKGROUND: Prucalopride is a selective and specific 5-hydroxytryptamine(4) receptor agonist that is known to increase stool frequency and to accelerate colonic transit. AIM: To investigate the effect of prucalopride on high-amplitude propagated contractions and segmental pressure waves in healthy volunteers. METHODS: After 1 week of dosing (prucalopride or placebo in a double-blind, randomized, crossover fashion), colonic pressures were recorded in 10 healthy subjects using a solid-state pressure catheter with six sensors spaced 10 cm apart. Subjects kept diary records of their bowel habits (frequency, consistency and straining). High-amplitude propagated contractions were analysed visually, comparing their total numbers and using 10-min time windows. Segmental pressure waves were analysed using computer algorithms, quantifying the incidence, amplitude, duration and area under the curve of all detected peaks. RESULTS: When taking prucalopride, stool frequency increased, consistency decreased and subjects strained less. Prucalopride just failed to increase the total number of high-amplitude propagated contractions (P=0.055). The number of 10-min time windows containing high-amplitude propagated contractions was increased by prucalopride (P=0.019). Prucalopride increased the area under the curve per 24 h (P=0.026). CONCLUSIONS: The 5-hydroxytryptamine(4) receptor agonist prucalopride stimulates high-amplitude propagated contractions and increases segmental contractions, which is likely to be the underlying mechanism of its effect on bowel habits in healthy volunteers.

Adult↗