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Biomedical subjects

B Coulie

Publications and source records attributed to B Coulie.

34 records · Page 2Linked to original sources
PubMed2000

Effects of alosetron on gastrointestinal transit time and rectal sensation in patients with irritable bowel syndrome.

BACKGROUND: Alosetron, a 5-HT3-receptor antagonist, relieves abdominal pain and improves bowel function in non-constipated, female patients with irritable bowel syndrome. 5-HT3 antagonists delay colonic transit, increase colonic compliance, and increase small intestinal water absorption. AIM: To evaluate the effects of alosetron on gastrointestinal and colonic transit, rectal compliance and rectal sensation in irritable bowel syndrome. METHODS: A double-blind, placebo-controlled, two-dose study of alosetron was performed in 25 non-constipated irritable bowel syndrome patients, with paired studies before and after 4 weeks of treatment with placebo (n=5), 1 mg alosetron (n=10) or 4 mg (n=10) alosetron b.d. Gastrointestinal and colonic transit were measured by scintigraphy. Rectal compliance and sensation were assessed by rectal balloon distention with a barostat. RESULTS: There was a trend (P=0.06) for 1 mg alosetron to increase rectal compliance (median pressure at half maximum volume 11 mmHg after alosetron vs. 15.6 mmHg before alosetron). The 1 mg b.d. alosetron dose non-significantly retarded proximal colonic transit. Alosetron and placebo reduced sensory scores relative to baseline values; none of the changes induced by alosetron was significant relative to placebo. CONCLUSIONS: Alosetron had no significant effect on gastrointestinal transit or rectal sensory and motor mechanisms in non-constipated irritable bowel syndrome patients in this study. Alosetron's effects on colonic sensorimotor function and central sensory mechanisms deserve further evaluation.

Adult↗
PubMed2000

Synaptic transmission induces transient Ca2+ concentration changes in cultured myenteric neurones.

The enteric nervous system controls most of the gastrointestinal functions. We applied confocal microscopy and the Ca2+ indicator Fluo-3 as an optical approach to study synaptic activation in cultures of myenteric neurones. The optical recording of [Ca2+]i (the intracellular Ca2+ concentration) was used to monitor activation, since [Ca2+]i is crucial in the coupling between neuronal excitation and the activation of several intracellular events. Extracellular fibre tract stimulation (2 s, 30 Hz) caused a transient [Ca2+]i rise in a subset of neurones (50%). These transients lasted for 5.2 s (n=36), with an average amplitude of 3.4 +/- 1.3 times the basal concentration. The removal of extracellular Ca2+ (n=15) or the application of 10-6 M tetrodotoxin (n=16) blocked this response. The N-type Ca2+-channel blocker omega-conotoxin (5 x 10 -7M) abolished the [Ca2+]i increase, while blockade of L-type and P/Q type Ca2+ channels had no effect. Single stimuli evoked a [Ca2+]i rise in the processes. omega-conotoxin-sensitive postsynaptic events required repetitive stimulation. Cholinergic blockade did not inhibit the [Ca2+]i rise in all neurones, suggesting that, besides acetylcholine, other neurotransmitters are involved. Optical imaging of [Ca2+]i can be used to study synaptic spread of activation in enteric neuronal circuits expressed in culture.

Action Potentials↗
PubMed2000

Recombinant human neurotrophic factors accelerate colonic transit and relieve constipation in humans.

BACKGROUND & AIMS: The aim of this study was to assess the effects of recombinant human brain-derived neurotrophic factor (r-metHuBDNF) and recombinant human neurotrophic factor 3 (r-metHuNT-3) on gastrointestinal motor functions in healthy people and in patients with constipation. METHODS: Gastrointestinal and colonic transit was measured by scintigraphy before and after 2 weeks of treatment. Daily diaries documented symptoms over 6 weeks before, during, and after treatment. In a randomized study of healthy subjects, 40 received 100 microg/kg r-metHuBDNF or placebo subcutaneously (SC) daily. In a separate study, 8 healthy subjects and 8 patients with constipation received 300 microg/kg r-metHuNT-3 SC thrice weekly. RESULTS: r-met-HuBDNF accelerated overall and proximal colonic emptying (P<0.05) in health. r-metHuNT-3 accelerated overall colonic transit in health and constipation (all P<0.05) and gastric and small bowel transit (both P<0.05) in health. r-metHuBDNF tended to increase stool frequency compared with placebo in health (P = 0.09). r-metHuNT-3 increased stool frequency (P = 0.05) and facilitated passage of stool (P < 0.01) in constipated patients. The effects on stool frequency started within 3 days of the beginning of neurotrophin administrations and lasted up to 5 days after treatment ended. r-metHu neurotrophic factors were well tolerated, although half of the participants in the 2 studies developed injection site reactions or paresthesiae. CONCLUSIONS: Exogenous neurotrophic factors stimulate human gut motility in health and constipation.

Adult↗
PubMed2000

Influence of sumatriptan on gastric fundus tone and on the perception of gastric distension in man.

BACKGROUND: In animals, activation of 5-HT(1) like receptors causes a relaxation of the gastric fundus through the activation of intrinsic inhibitory neurones. AIMS: To investigate the effect of sumatriptan, an agonist at enteric neuronal 5-HT(1) receptors, on fasting fundus tone and sensitivity to gastric distension in man. METHODS: A gastric barostat was used to study the effect of placebo and sumatriptan, 6 mg subcutaneously, on basal fundic tone in healthy subjects. In addition, stepwise isobaric and isovolumetric gastric distensions were performed and perception was measured before and after the administration of placebo and sumatriptan. RESULTS: Placebo had no significant effects on gastric tone and on perception. Sumatriptan induced an immediate relaxation of the gastric fundus, reflected by an intragastric volume increase of 209 (39) ml (p<0.0005). After sumatriptan, intragastric pressures at the thresholds for perception or discomfort were not significantly altered. However, the intragastric volumes and the corresponding calculated wall tensions at perception and discomfort thresholds were significantly increased. CONCLUSIONS: Administration of the 5-HT(1) receptor agonist sumatriptan induces a relaxation of the gastric fundus in man, allowing larger intragastric volumes before thresholds for perception or discomfort are reached. The effects of sumatriptan on the gastric fundus may have therapeutic potential in the treatment of patients with functional dyspepsia.

Adult↗
PubMed1999

Neurochemical coding of myenteric neurons in the guinea-pig antrum.

Electrophysiological studies of myenteric neurons in the guinea-pig antrum suggest that different neuroactive compounds are involved in synaptic transmission. It is not known what neurotransmitters and neuropeptides are present and to what extent they colocalize. Immunohistochemical stainings were performed on whole-mount preparations of the guinea-pig antrum. Immunoreactivity for neuron-specific enolase was used as a general marker and was set at 100%. There was no overlap between cholinergic and nitrergic neurons, resulting in two separate subpopulations. The presence of choline acetyltransferase immunoreactivity was used to identify the cholinergic subset, which accounted for 56% of the cells. Immunoreactivity for nitric oxide synthase, on the other hand, was displayed in 40.7% of the neurons. Substance-P immunoreactivity was present in 37.4% of the cells and vasoactive intestinal peptide and neuropeptide Y in 21.7% and 28.6%, respectively. Small subsets of neurons had immunoreactivity for serotonin (3.9%), calretinin (6.8%) and calbindin (0.5%). Colocalization studies revealed several subgroups of neurons, containing one or more of the screened markers. Though some similarity is found in the chemical coding of the antrum compared to that of the small intestine and the corpus, remarkable differences can be seen in the occurrence of some subpopulations. Cholinergic neurons are not as predominant as in other parts of the gut, serotonin presence is doubled and some vasointestinal-peptide-positive neurons express substance P. These differences might reflect the highly specialized function of the antrum; however, the exact role of these classes remains to be established.

Animals↗
PubMed1999

Descending perineum syndrome: audit of clinical and laboratory features and outcome of pelvic floor retraining.

OBJECTIVE: Our aim was to retrospectively analyze the Mayo Clinic experience of descending perineum syndrome from 1987-1997. METHODS: Clinical records were abstracted for demographic features, risk factors, results of anorectal and defecation tests, and a mailed questionnaire evaluated outcome and current symptoms. RESULTS: All results are mean +/- SD. Clinically, 39 patients (38 women, one man), mean age 53+/-14 yr, presented with constipation (97%), incomplete rectal evacuation (92%), excessive straining (97%), digital rectal evacuation (38%), and fecal incontinence (15%). Laboratory tests showed anal sphincter resting pressure was 54+/-26 mm Hg, and squeeze pressure was 96+/-35 mm Hg; expulsion from the rectum of a 50-ml balloon required > 200 g added weight in 27%; perineal descent was 4.4+/-1 cm (normal < 4 cm) by scintigraphy. Scintigraphic evacuation, rectoanal angle change during defecation, and perineal descent were abnormal in 23%, 57%, and 78% of the patients, respectively. Associated features included female gender (96%), multiparity with vaginal delivery (55%), hysterectomy or cystocele/rectocele repair (74%). On follow-up, 64% responded; 17 of these 25 responders underwent pelvic floor retraining. At 2-yr median follow-up (range, 1-6 yr), 12 still experienced constipation or excessive straining; their perineal descent was greater than in patients who responded to retraining (p = 0.005). CONCLUSIONS: Descending perineum syndrome is identifiable by clinical history and examination, and the most prevalent abnormality on testing is perineal descent > 4 cm; rectal balloon expulsion is an insensitive screening test for descending perineum syndrome. Pelvic floor retraining is a suboptimal treatment for this chronic disorder of rectal evacuation; the extent of perineal descent appears to be a useful predictor of response to retraining.

Anal Canal↗
PubMed1999

Effect of sumatriptan, a 5HT1 agonist, on the frequency of transient lower esophageal sphincter relaxations and gastroesophageal reflux in healthy subjects.

OBJECTIVE: Meals increase the rate of transient lower esophageal sphincter (LES) relaxations, in part by gastric distension. The 5HT1 agonist sumatriptan reduces fasting fundic tone, prolongs the meal-induced fundic relaxation, and delays gastric emptying. We therefore hypothesized that sumatriptan might have a significant effect on the rate of postprandial transient LES relaxations and gastroesophageal reflux. We aimed to study the effect of sumatriptan on postprandial transient LES relaxations and reflux in healthy subjects. METHODS: Esophageal manometry and pH monitoring were performed in 13 healthy volunteers for 30 min before and 90 min after a semiliquid meal (790 kcal). Sumatriptan 6 mg subcutaneous (s.c.) or s.c. placebo were administered on separate days 30 min after the meal. RESULTS: Sumatriptan significantly increased postprandial LES pressure from 11.0 +/- 1.2 mm Hg to 17.6 +/- 1.2 mm Hg (p < 0.05). However, reflux events were not diminished. In the contrary, reflux was more frequent after sumatriptan than after placebo (3 [1.5-4.5]/30 min vs 2 [0-3]/30 min, p < 0.05). Transient LES relaxations were more frequent after sumatriptan, particularly in the second 30-min period after drug administration (3 [2.5-5]/30 min vs 2 [1.5-2]/30 min, p < 0.05). CONCLUSIONS: Sumatriptan prevents the natural decay in rate of transient LES relaxations that occurs after a meal and favors the occurrence of gastroesophageal reflux despite increasing LES pressure. The sustained postprandial high rate of transient LES relaxations after sumatriptan may be a consequence of a prolonged fundus relaxation and retention of meal in the proximal stomach.

Adolescent↗
PubMed1999

Intestinal pseudo-obstruction.

Pseudo-obstruction syndromes are increasingly recognized in clinical practice. They result from impairment of intrinsic neuromuscular or extrinsic control of gut motility. Typically, pseudo-obstruction syndromes result in features suggestive of mechanical obstruction and bowel dilatation in the absence of any demonstrable obstruction or mucosal disease. The syndrome may affect any region of the gut. Less severe variants without bowel dilatation are diagnosed by measurement of gastrointestinal transit and pressure profiles. The aims of treatment are restoration of nutrition and hydration, symptom relief, normalization of intestinal propulsion with prokinetics, and suppression of bacterial overgrowth. Surgery plays a limited role, adjunctive to medical treatment, facilitating enteral nutrition and decompression by means of jejunostomy. Infrequently, resection of localized disease or intestinal transplantation are indicated. The roles of intestinal pacemakers (interstitial cells of Cajal) and genetic mutations in the etiology of pseudo-obstruction, as well as the cost-benefit ratio of transplantation for pseudo-obstruction, will be clarified in the future.

Dilatation, Pathologic↗
PubMed1999

Role of nitric oxide in fasting gastric fundus tone and in 5-HT1 receptor-mediated relaxation of gastric fundus.

Fasting gastric fundus tone is maintained by continuous cholinergic input. 5-Hydroxytryptamine-1 (5-HT1) receptor activation decreases gastric fundus tone in humans. Whether this fundus-relaxing effect is mediated via inhibition of cholinergic input or via activation of a nitrergic pathway is unknown. The aim of the present study was to determine the effect of nitrergic inhibition on feline gastric fundus tone and on 5-HT1 receptor-mediated relaxation of the fundus. Administration of Nomega-nitro-L-arginine methyl ester (L-NAME) alone caused a significant decrease of the mean baseline volume (P < 0.005), which was restored completely by addition of L-arginine. Sumatriptan caused a dose-dependent relaxation of the gastric fundus (P < 0.0005). This relaxation was inhibited by L-NAME (P < 0.02) and was restored by prior administration of L-arginine. Buspirone did not cause any change in mean baseline volume, whereas the sumatriptan-induced relaxation was not affected by prior administration of NAN-190. Our data indicate that fasting fundus tone relies not only on continuous cholinergic input but also on continuous nitrergic input, implying that fasting fundus tone is maintained by the balance of a cholinergic and nitrergic drive. Furthermore, fundus relaxation via 5-HT1 receptor activation is mediated through activation of a nitrergic pathway.

Animals↗
PubMed1998

Role of impaired gastric accommodation to a meal in functional dyspepsia.

BACKGROUND & AIMS: Impaired accommodation of the proximal stomach to a meal has been reported in functional dyspepsia, but its relevance to symptoms is unclear. The aim of this study was to test the hypothesis that impaired gastric accommodation causes early satiety. METHODS: A gastric barostat was used to study postprandial fundus relaxation in 35 healthy subjects and 40 patients with functional dyspepsia. Gastric emptying, Helicobacter pylori status, sensitivity to gastric distention, and a dyspepsia symptom score were obtained from all patients. In addition, the effect of sumatriptan, a fundus-relaxing 5-hydroxytryptamine1 agonist, on gastric accommodation and on early satiety in dyspeptic patients was studied. RESULTS: Impaired gastric accommodation to a meal was found in 40% of the patients. In univariate analysis, this was associated with early satiety and weight loss but not with hypersensitivity to gastric distention, presence of H. pylori, or delayed gastric emptying. In a multivariate analysis, only early satiety was associated with impaired gastric accommodation. Sumatriptan restored gastric accommodation, thereby significantly improving meal-induced satiety. CONCLUSIONS: Impaired relaxation of the proximal stomach to a meal is present in a high proportion of patients with functional dyspepsia. It is associated with symptoms of early satiety. Restoring gastric accommodation with a fundus-relaxing drug improves early satiety.

Adult↗
PubMed1998

The influence of cisapride on gastric tone and the perception of gastric distension.

BACKGROUND: Delayed gastric emptying, impaired gastric accommodation to a meal and hypersensitivity to gastric distension have been implied in the pathophysiology of functional dyspepsia. Dyspeptic patients are often treated with the prokinetic drug cisapride. AIM: To assess the effects of cisapride on perception of gastric distension and gastric accommodation to a meal. METHODS: Eighteen healthy volunteers underwent a gastric barostat study on two occasions, after pretreatment with placebo or cisapride 10 mg q.d.s. Graded isobaric and isovolumetric distensions were performed until the subjects reported discomfort. Volume and pressure changes were recorded and perception was scored by a questionnaire. In 10 volunteers, the amplitude of the gastric accommodation to a mixed liquid meal was also measured. RESULTS: Pre-treatment with cisapride significantly lowered thresholds for perception and for discomfort, both during isobaric (4.3 +/- 0.7 vs. 3.2 +/- 0.7 and 12.2 +/- 1.2 vs. 9.2 +/- 0.9 mmHg above minimal distending pressure (MDP), respectively, P < 0.05) and isovolumetric (256 +/- 46 vs. 200 +/- 35 and 644 +/- 36 vs. 511 +/- 40 mL, respectively, P < 0.05) distensions. Cisapride significantly enhanced the size of the meal-induced fundus relaxation (143 +/- 37 vs. 270 +/- 50 mL, P < 0.05). CONCLUSIONS: Cisapride enhances both the perception of gastric distension and the gastric accommodation to a meal. These data suggest that cisapride may provide benefit to patients with impaired postprandial relaxation of the fundus.

Adult↗
PubMed1998

Actions of the 5-hydroxytryptamine 1 receptor agonist sumatriptan on interdigestive gastrointestinal motility in man.

BACKGROUND: Pharmacological studies of the enteric nervous system have shown the presence of several subtypes of 5-hydroxytryptamine (5HT) receptor, which might be involved in control of the migrating motor complex. AIMS: To study the effect of sumatriptan, an agonist of enteric neuronal 5HT1p receptors, on interdigestive motility in man. SUBJECTS AND METHODS: In 12 healthy subjects, interdigestive motility was recorded manometrically in the upper gastrointestinal tract. In seven subjects blood samples were drawn every 15 minutes for radioimmunoassay of motilin and somatostatin. After two phase 3s of the migrating motor complex, 6 mg of sumatriptan was administered subcutaneously. Recording continued until two more phase 3s had occurred. RESULTS: Sumatriptan induced a premature phase 3 in the jejunum after a median of 10 (8) minutes. The duration of the migrating motor complex cycle was shortened at the expense of phase 2. After sumatriptan, plasma somatostatin concentrations were reduced and gastric phase 3s were suppressed, although median motilin concentrations and the occurrence of plasma motilin peaks were not affected. Phase 3s of the migrating motor complex preceding sumatriptan were associated with motilin peaks, while phase 3s after sumatriptan were not. Furthermore, pretreatment with sumatriptan prevented the induction of a gastric phase 3 by the motilin agonist erythromycin. CONCLUSIONS: Administration of the 5HT1P receptor agonist sumatriptan induces a premature intestinal phase 3, suppresses gastric phase 3s, prevents induction of a gastric phase 3 by erythromycin, and reduces plasma somatostatin concentrations.

Adult↗
PubMed1998

Involvement of two different pathways in the motor effects of erythromycin on the gastric antrum in humans.

BACKGROUND: During the interdigestive state in humans, erythromycin 40 mg induces a premature activity front that starts in the stomach, while erythromycin 200 mg induces a prolonged period of enhanced antral contractile activity. AIMS: To study the involvement of a cholinergic pathway in the motor effects of erythromycin using the muscarinic antagonist atropine and the neural 5-HT1 receptor agonist sumatriptan. METHODS: In 30 healthy volunteers, fasted antroduodenojejunal motor activity was studied by stationary manometry. Placebo (n = 10), atropine (15 micrograms/kg intravenous bolus plus 15 micrograms/kg/h over 30 minutes; n = 10), or sumatriptan (6 mg subcutaneously; n = 10) was administered, followed by infusion of erythromycin 40 mg or 200 mg. RESULTS: After placebo, erythromycin 40 mg induced a premature activity front with gastric onset after 19.1 (1.7) minutes in all volunteers. After atropine, erythromycin 40 mg failed to induce a premature activity front during a 60 minute period in all volunteers (p < 0.001), while sumatriptan prevented the induction of a premature activity front during a 60 minute period in all but one volunteer (p < 0.005). The number of antral contractions and their mean amplitude in the 60 minutes after erythromycin 200 mg did not differ significantly after atropine or sumatriptan versus placebo. CONCLUSIONS: The antral motor effects of erythromycin in humans are mediated via different pathways. The induction of a premature activity front is mediated through activation of an intrinsic cholinergic pathway, while the induction of enhanced antral contractile activity may be mediated via a pathway potentially involving activation of a muscular receptor.

Anti-Bacterial Agents↗
PubMed1998

5-Hydroxytryptamine-1 receptor activation inhibits endocrine pancreatic secretion in humans.

The selective 5-hydroxytryptamine-1 receptor agonist sumatriptan inhibits exocrine pancreatic function in humans. No data are available on the effect of sumatriptan on fasting and postprandial endocrine pancreatic function in humans. To elucidate the influence of 5-hydroxytryptamine-1 receptor activation by sumatriptan on endocrine pancreatic function and blood glucose homeostasis, we determined plasma levels of somatostatin, glucagon, pancreatic polypeptide, insulin, and C-peptide before and after subcutaneous administration of sumatriptan (6 mg) in seven healthy volunteers, and we measured blood glucose and insulin plasma levels during an oral glucose tolerance test after placebo and after subcutaneous administration of sumatriptan (6 mg) in seven healthy volunteers. Sumatriptan significantly decreased the mean plasma levels of somatostatin, glucagon, pancreatic polypeptide, insulin and C-peptide (P < 0.001) and also significantly decreased mean and peak plasma levels of insulin after an oral glucose challenge (P < 0.02 and P = 0.04, respectively) without affecting glucose homeostasis. From our study, we speculate that activation of the 5-hydroxytryptamine-1 receptor inhibits endocrine pancreatic secretion.

Adult↗
PubMed1997

Sumatriptan, a selective 5-HT1 receptor agonist, induces a lag phase for gastric emptying of liquids in humans.

Sumatriptan, a 5-hydroxytryptamine1 (5-HT1) receptor agonist at enteric neuronal 5-HT receptors, causes a relaxation of the gastric fundus and inhibition of antral contractile activity. The present study examined the effect of sumatriptan on gastric emptying of solids and liquids in humans. In eight healthy subjects the gastric emptying rate for liquids and solids was measured using the carbon-labeled glycine and octanoic acid breath test after subcutaneous administration of placebo or sumatriptan. Sumatriptan increased the gastric half-emptying time of liquids (P < 0.0005) and induced a prolonged lag phase for liquids (P < 0.0005) in all subjects. Sumatriptan increased gastric half-emptying time (P < 0.005) and the lag phase of solids (P < 0.05) in all subjects. In two healthy subjects gastric emptying of liquids and solids after subcutaneous administration of sumatriptan was studied by radioscintigraphy. Radioscintigraphy confirmed the delayed emptying and the prolonged lag phases after sumatriptan. In conclusion, sumatriptan delays gastric emptying of solids and liquids in healthy subjects. Moreover, sumatriptan induces a lag phase for liquids. The mechanism by which sumatriptan alters gastric emptying remains to be studied.

Adult↗