Biomedical subjects

J Janssens

Publications and source records attributed to J Janssens.

At least 37 records · Page 2Linked to original sources

PubMed2005

Dyspeptic patients with visceral hypersensitivity: sensitisation of pain specific or multimodal pathways?

BACKGROUND AND AIMS: Patients with functional dyspepsia who have hypersensitivity to gastric distension have more prevalent pain, suggesting the presence of hyperalgesia. It is unclear whether this reflects activation of pain specific afferent pathways or multimodal afferent pathways that also mediate non-painful sensations. In the former case, hyperalgesia should occur when intensity of non-painful sensations is still low. The aim of the study was to analyse whether the symptom profile during gastric dissentions in functional dyspepsia patients with hyperalgesia reflects sensitisation of pain specific or multimodal pathways. METHODS: Forty eight consecutive dyspeptic patients (35 female) underwent gastric sensitivity testing with a barostat balloon using a double random staircase protocol. At the end of every distending step, patients scored perception of upper abdominal sensations on a graphic 0-6 rating scale and completed visual analogue scales (VAS 0-100 mm) for pain, nausea, satiety, and fullness. The end point was a rating scale of 5 or more. RESULTS: Hypersensitivity was present in 20 patients (40%); gastric compliance did not differ between normo- and hypersensitive patients. At maximal distension (score 5 or more), hypersensitive patients had significantly lower distending pressures and intra-balloon volumes, but similar VAS scores for pain, nausea, satiety, and fullness compared with normosensitive patients. In both normosensitive and hypersensitive patients, elevation of pain VAS scores with increasing distending pressures paralleled the elevation in VAS scores for nausea, satiety, and fullness. CONCLUSIONS: Hypersensitive dyspeptic patients reach the same intensity of painful and non-painful sensations as normosensitive patients but at lower distending pressures. Hyperalgesia occurs in hypersensitive dyspeptic patients at distending pressures that also induce intense non-painful sensations. These findings argue against isolated upregulation of pain specific afferents in functional dyspepsia patients with visceral hypersensitivity.

Adult↗

PubMed2005

Weakly acidic reflux in patients with chronic unexplained cough during 24 hour pressure, pH, and impedance monitoring.

BACKGROUND AND AIMS: Acid gastro-oesophageal reflux is one of the most important causes of chronic cough. The response to acid suppression in these patients is not as good as in patients with heartburn but improvement with antireflux surgery has been reported, suggesting the involvement of a non-acidic gastric component in the refluxate. Less acidic reflux may produce symptoms such as regurgitation or chest pain. We investigated whether chronic cough might be associated with weakly acidic reflux. METHODS: We studied 28 patients with chronic cough using 24 hour ambulatory pressure-pH-impedance monitoring. Manometry was used for precise recognition of cough and impedance-pHmetry to detect acid (pH <4), weakly acidic (pH 7-4), and weakly alkaline (impedance drops, pH >/=7) reflux. A symptom association probability (SAP) analysis was performed for each type of reflux. RESULTS: Analysis was completed in 22 patients with 24 cough events (5-92)/patient. The majority of cough events (69.4%) were considered "independent" of reflux whereas 30.6% occurred within two minutes of a reflux episode. Half of these (49%) were "reflux cough" sequences, involving acid (65%), weakly acidic (29%), and weakly alkaline (6%) reflux. Ten patients (45%) had a positive SAP between reflux and cough: five with acid, two with acid and weakly acidic, and three only with weakly acidic reflux. CONCLUSIONS: Ambulatory pressure-pH-impedance monitoring with SAP analysis allowed precise determination of the temporal association between cough and gastro-oesophageal reflux (acid, weakly acidic, and weakly alkaline) and identification of a subgroup of patients with chronic cough clearly associated with weakly acidic gastro-oesophageal reflux.

Adult↗

PubMed2004

Influence of a lipase inhibitor on gastric sensitivity and accommodation to an orally ingested meal.

BACKGROUND: Intraduodenal administration of lipids, through lipid digestion and release of cholecystokinin (CCK), induces viscero-visceral reflexes that affect gastric tone and sensitivity. It is unclear whether the same mechanisms control gastric function after an orally ingested meal. AIM: To evaluate the effect of orlistat, a selective lipase inhibitor, on gastric response to an orally administered meal. METHODS: Eighteen healthy volunteers participated in this study. They were treated for 5 days with orlistat (120 mg) or placebo t.d.s. in a double-blind randomized crossover design. During treatment, all subjects underwent a gastric barostat study, measurement of plasma CCK levels and a satiety drinking test. RESULTS: Although CCK plasma levels were significantly decreased, pre-treatment with orlistat failed to affect gastric compliance (72 +/- 6 mL/mm Hg and 64 +/- 6 mL/mm Hg, NS), gastric sensitivity (discomfort threshold 12.2 +/- 0.6 mm Hg vs. 10.9 +/- 0.6 mm Hg above minimal distending pressure, NS) or gastric accommodation (172 +/- 41 mL vs. 206 +/- 49 mL, NS) to an orally ingested meal. Furthermore, orlistat pre-treatment had no significant effect on the amount of calories ingested during a satiety drinking test (1329 +/- 88 kcal vs. 1217 +/- 115 kcal, NS). CONCLUSION: Administration of a lipase inhibitor does not affect gastric compliance, sensitivity to distension and accommodation to an orally ingested meal, and does not influence meal-induced satiety.

Adaptation, Physiological↗

PubMed2004

Neural regulation of tone in the oesophageal body: in vivo barostat assessment of volume-pressure relationships in the feline oesophagus.

Recent combined manometric-barostat studies demonstrated that the oesophageal body exhibits both peristaltic contractions and tone. This study further characterized the neural modulation of tone in the feline oesophageal body. Simultaneous oesophageal barostat and manometry were performed in 20 adult cats under ketamine sedation. Oesophageal tone and peristalsis were assessed in the distal smooth muscle oesophagus. Cholinergic modulation was studied using neostigmine, erythromycin, atropine and vagotomy. Nitrergic regulation was assessed using sildenafil to increase cellular cyclic guanosine monophosphate and the nitric oxide synthase blocker Nomega-nitro-l-arginine (l-NNA). The presence of a tonic contractile activity in the distal oesophageal body was confirmed. Peristaltic contractions proceeded along the oesophageal body over the background tonic contraction. Neostigmine and erythromycin enhanced (20-30%) whereas bilateral vagotomy and atropine strongly decreased oesophageal tone (50-60%). However, l-NNA increased (40%) and sildenafil decreased oesophageal tone (30%). Therefore, tonic contractile activity in the oesophageal body is mainly caused by a continuous cholinergic excitatory input. A nitric oxide inhibitory mechanism may have a complementary role in the regulation of oesophageal tone.

Animals↗

PubMed2004

Influence of continuous isobaric rectal distension on gastric emptying and small bowel transit in young healthy women.

Patients with slow transit constipation frequently have delayed gastric emptying. In animals rectal distensions inhibit gastrointestinal motility. In healthy volunteers isovolumetric rectal distensions delay upper gut transit. The purpose of this study was to determine the effect of continuous isobaric rectal distension on gastric emptying and oro-cecal transit in young females. Using validated 13C octanoic and lactose-[13C] ureide breath tests gastric half-emptying time and oro-cecal transit time for a meal were measured in 12 volunteers. The tests were repeated in randomized order: during isobaric balloon distension and during sham distension. Isobaric rectal distension was applied using a polyethylene bag connected to a barostat. Intraballoon pressure was kept just below the threshold for the urge sensation. Mean gastric half-emptying time during rectal distension (92.3 +/-5.1 min) was significantly higher than during sham distension (78.8 +/- 4 min; P = 0.015). Mean oro-cecal transit time during rectal distension (391.3 +/-29.1 min) and sham distension (328.8 +/- 38.4 min) were not significantly different. In conclusion, these findings indicate that isobaric rectal distension inhibits gastric emptying, but not small bowel transit in young healthy women. Studies in patients with constipation are indicated.

Adult↗

PubMed2004

Gastroesophageal reflux disease poorly responsive to single-dose proton pump inhibitors in patients without Barrett's esophagus: acid reflux, bile reflux, or both?

OBJECTIVES: Studies using ambulatory pH and esophageal bile reflux monitoring (Bilitec) have shown that both acid reflux and duodeno-gastro-esophageal reflux (DGER) frequently occur in patients with gastroesophageal reflux disease (GERD). A subset of patients with GERD has persistent reflux symptoms in spite of standard doses of proton pump inhibitors (PPIs). The aim of the present study was to investigate the role of acid and DGER in patients with reflux disease poorly responsive to PPIs. METHODS: Sixty-five patients (32 men, 44 +/- 2 yr) without Barrett's esophagus and with persistent heartburn or regurgitation during standard PPI doses were studied. They underwent upper gastrointestinal endoscopy and simultaneous 24-h ambulatory pH and Bilitec monitoring while PPIs were continued. RESULTS: Thirty-three patients (51%) had persistent esophagitis. Seven patients (11%) had only pathological acid exposure, 25 (38%) had only pathological DGER exposure, and 17 (26%) had pathological exposure to both acid and DGER. Acid exposure under PPI was positive in only 37%, but adding Bilitec increased the diagnoses of persistent reflux to 75%. Patients with persistent esophagitis had similar acid exposure, but significantly higher DGER exposure than those without esophagitis. The highest prevalence of esophagitis was found in patients with pathological exposure to both acid and DGER; symptoms did not differ according to the type of reflux. CONCLUSIONS: Combined pH and Bilitec monitoring is superior to pH monitoring alone in demonstrating ongoing pathological reflux in patients with medically poorly responsive reflux disease.

Adult↗

PubMed2004

Differences in the sensorimotor response to distension between the proximal and distal stomach in humans.

BACKGROUND: It is not known which region of the stomach is responsible for symptom generation or whether symptoms induced by gastric distension are region specific. Also, it is unclear whether low level gastric distension has a modulatory role on gastric tone and mechanosensitivity. AIMS: To define differences in the sensorimotor response to distension between proximal and distal gastric distension, and to determine the effects of low level gastric distension on gastric tone and mechanosensitivity. METHODS: In 14 healthy volunteers, a double barostat assembly incorporating a distal (antral) and proximal (fundic) bag was introduced into the stomach. Pressure sensitivity tests with either bag were performed with and without simultaneous background distension of the other bag in a randomised manner. Proximal gastric accommodation to a meal was measured with and without simultaneous distal gastric distension. RESULTS: The distal stomach was less compliant than the proximal stomach to low level distension. Thresholds for first perception and discomfort, and symptom profiles did not differ between distal and proximal gastric distension. Simultaneously applied low level gastric distension of one segment did not affect gastric mechanosensitivity of the other segment. Both the proximal and distal stomach relax after ingestion of a meal. Simultaneous low level antral distension decreases proximal gastric accommodation to a meal. CONCLUSIONS: Compared with the proximal stomach, the distal stomach is less compliant but its mechanosensitivity is not different. Symptoms induced by gastric distension are not region specific and no spatial summation occurred. Meal induced relaxation occurs both in the proximal and distal stomach.

Adult↗

PubMed2004

Oesophageal clearance of acid and bile: a combined radionuclide, pH, and Bilitec study.

BACKGROUND: Studies combining pH and Bilitec monitoring found a high prevalence of both acid and duodeno-gastro-oesophageal reflux in severe reflux disease. Clearance of refluxed material is a major defence mechanism against reflux. Several studies have been devoted to oesophageal acid clearance but oesophageal clearance of refluxed duodenal contents (DC) has rarely been addressed. AIM: To compare oesophageal acid and DC clearance. METHODS: Ten healthy volunteers (five women, mean age 23 (1) years) were studied. Firstly, a balloon tip catheter, positioned in the duodenum under fluoroscopy, was used to aspirate DC after stimulation by a high caloric liquid meal (200 ml, 300 kcal). During the second session, pH and Bilitec probes were positioned 5 cm above the lower oesophageal sphincter and a small infusion catheter was introduced into the proximal oesophagus. The subject was placed supine under a gamma camera. One of two different solutions (DC mixed with 0.2 mCi Tc99m pertechnetate or citric acid (pH 2) mixed with 0.2 mCi Tc99m pertechnetate) was infused into the proximal oesophagus and the subject was instructed to swallow at 20 second intervals. Clearance was assessed using scintigraphy (dynamic acquisition, one frame per second in the anterior view; calculation of time to clear peak counts to background level), pH (time to pH<4) or Bilitec (time absorbance >0.14) monitoring, with or without continuous saliva aspiration. Each condition was studied twice in a randomised design; measurement time was four minutes, interrupted by water flushing, with a two minute rest period. Results are given as mean (SEM) and were compared by Student's t test and Pearson correlation. RESULTS: Scintigraphic evaluation showed a volume clearance time of 29 (3) seconds for acid and 28 (9) seconds for DC (NS). Saliva aspiration had no significant influence on volume clearance of acid or DC (28 (4) and 30 (13) seconds, respectively; NS). pH monitoring showed an acid clearance time of 217 (15) seconds, which was significantly prolonged to 324 (30) seconds during saliva aspiration (p<0.05). Bilitec monitoring showed a DC clearance time of 131 (27) seconds, which was not significantly prolonged by saliva aspiration (176 (36) seconds; p = 0.08). DC clearance was faster than acid clearance, either without or with saliva aspiration (p<0.055 and p<0.05, respectively). CONCLUSIONS: Under experimental conditions, liquid acid and DC solutions have comparable volume clearances. Chemical clearance occurs slightly faster for DC than for acid, and saliva plays a major role in the clearance of acid only.

Adult↗

PubMed2003

Influence of tegaserod on proximal gastric tone and on the perception of gastric distension.

BACKGROUND: Tegaserod, a 5-hydroxytryptamine-4 receptor agonist, enhances gastric emptying, but its effects on proximal stomach function have not been studied. AIM: To study the effect of tegaserod on gastric compliance, accommodation and perception of distension in humans. METHODS: Nineteen healthy volunteers (10 females; mean age, 23.9 years) were studied on three separate occasions after 7 days of treatment with placebo, tegaserod 2 mg b.d. or tegaserod 6 mg b.d. in a double-blind, randomized, three-way cross-over design. After the introduction of a barostat bag, stepwise distensions were performed to determine gastric compliance and sensitivity, and a mixed liquid meal was administered in isobaric mode to assess accommodation. RESULTS: Tegaserod had no effect on the pressures or volumes inducing first perception or discomfort. Tegaserod 6 mg b.d. enhanced fasting gastric compliance compared with placebo. Pre-prandial and post-prandial intra-balloon volumes were significantly higher after 6 mg b.d. than after placebo. Both tegaserod 2 and 6 mg b.d. shortened the time to maximum post-prandial intra-balloon volume. The amplitude of meal-induced gastric relaxation (post-prandial minus pre-prandial volumes) did not differ between the treatment arms. CONCLUSION: In humans, tegaserod allows for larger intra-balloon volumes both before and after a meal. These findings warrant the investigation of the therapeutic potential of tegaserod in dyspeptic patients with impaired accommodation.

Adult↗

PubMed2003

Differential effects of baclofen on lower oesophageal sphincter pressure and proximal gastric motility in humans.

BACKGROUND: The gamma-aminobutyric acid receptor type B agonist, baclofen, inhibits transient lower oesophageal sphincter relaxations by influencing a vagal pathway. Although post-prandial proximal gastric function, which is vagally mediated, is important in the occurrence of transient lower oesophageal sphincter relaxations, the effects of baclofen on post-prandial proximal gastric motility in humans remains undetermined. AIM: To determine the effects of baclofen on post-prandial lower oesophageal sphincter function and proximal gastric motility in healthy subjects. METHODS: In 11 healthy volunteers, a barostat bag and an oesophageal manometric catheter with a sleeve were simultaneously positioned; 40 mg of oral baclofen or placebo was then given in a randomized, double-blind manner. Subsequently, the intragastric bag volume, oesophageal and lower oesophageal sphincter pressure and oesophageal pH were recorded during the 90 min before and 120 min after a meal. RESULTS: During the post-prandial period, unlike the fasting period, baclofen decreased the rate of transient lower oesophageal sphincter relaxations and increased the basal lower oesophageal sphincter pressure compared with placebo. However, the meal-induced decrease in the tone and phasic contractility of the fundus was not affected by baclofen. CONCLUSION: The gamma-aminobutyric acid receptor type B agonist, baclofen, has a potent effect on post-prandial lower oesophageal sphincter motility without altering post-prandial proximal gastric motility, suggesting differential effects of baclofen on different signals of gastrointestinal vagal afferents.

Adult↗

PubMed2003

Influence of the selective serotonin re-uptake inhibitor, paroxetine, on gastric sensorimotor function in humans.

BACKGROUND: The role of 5-hydroxytryptamine in the control of gastric fundus tone in humans is still unknown. Selective 5-hydroxytryptamine re-uptake inhibitors act both centrally and peripherally to enhance the availability of physiologically released 5-hydroxytryptamine. AIM: To study the influence of a selective 5-hydroxytryptamine re-uptake inhibitor, paroxetine, on gastric fundus tone, on the perception to gastric distension and on gastric accommodation to a meal. METHODS: Sixteen healthy volunteers underwent a gastric barostat study on two occasions, after pre-treatment with placebo or paroxetine, 20 mg/day. Graded isobaric and isovolumetric distensions were performed and perception was scored by a questionnaire. Subsequently, the amplitude of the gastric accommodation to a mixed liquid meal was also measured. RESULTS: Pre-treatment with paroxetine did not alter the thresholds for perception and discomfort during isobaric (4.7 +/- 2.3 vs. 4.0 +/- 2.0 mmHg and 13.3 +/- 3.1 vs. 12.7 +/- 2.3 mmHg above the minimum intragastric distending pressure, N.S.) and isovolumetric (307 +/- 90 vs. 417 +/- 114 mL and 772 +/- 74 vs. 750 +/- 76 mL, N.S.) distensions. Paroxetine significantly enhanced the amplitude of the meal-induced fundus relaxation (136 +/- 51 vs. 255 +/- 43 mL, P < 0.05). CONCLUSIONS: Pre-treatment with paroxetine enhances gastric accommodation to a meal. These data suggest that the release of 5-hydroxytryptamine, probably at the level of the enteric nervous system, is involved in the control of the accommodation reflex in humans, and that paroxetine may be beneficial to patients with impaired post-prandial fundus relaxation.

Adult↗

PubMed2003

Electrical stimulation reveals complex neuronal input and activation patterns in single myenteric guinea pig ganglia.

The myenteric plexus plays a key role in the control of gastrointestinal motility. We used confocal calcium imaging to study responses to electrical train stimulation (ETS) of interganglionic fiber tracts in entire myenteric ganglia of the guinea pig small intestine. ETS induced calcium transients in a subset of neurons: 52.2% responded to oral ETS, 65.4% to aboral ETS, and 71.7% to simultaneous oral and aboral ETS. A total of 41.3% of the neurons displayed convergence of oral and aboral ETS-induced responses. Responses could be reversibly blocked with TTX (10(-)6 M), demonstrating involvement of neuronal conduction, and by removal of extracellular calcium. omega-Conotoxin (5 x 10(-7) M) blocked the majority of responses and reduced the amplitude of residual responses by 45%, indicating the involvement of N-type calcium channels. Staining for calbindin and calretinin did not reveal different response patterns in these immunohistochemically identified neurons. We conclude that, at least for ETS close to a ganglion, confocal calcium imaging reveals complex oral and aboral input to individual myenteric neurons rather than a polarization in spread of activity.

Animals↗

PubMed2003

Gemcitabine combined with cisplatin as first-line treatment in patients with epithelial ovarian cancer: a phase II study.

OBJECTIVE: This phase II study was performed to evaluate the activity and toxicity of gemcitabine plus cisplatin as first-line treatment of advanced epithelial ovarian cancer. METHODS: Chemonaive patients with histologically or cytologically confirmed FIGO stage III or IV epithelial ovarian carcinoma were enrolled. Patients received cisplatin 75 mg/m(2) on Day 1 and gemcitabine 1250 mg/m(2) on Days 1 (after cisplatin) and 8 of a 21-day cycle. RESULTS: Of the 42 female patients (median age 60 years) enrolled, 81% had a Zubrod performance status of 0 or 1. Among the 37 response-evaluable patients, there were 5 (13.5%) pathological complete responses (CRs), 16 (43.2%) pathological partial responses (PRs), and 3 (8.1%) clinical PRs, for an overall response rate of 64.9% (95% CI: 47.4-79.8%) and a pathological response rate of 56.8%. Per an intent-to-treat analysis, the overall response rate was 57.1% (95% CI: 41.0-72.3%). After a median follow-up time of 15.8 months, the median survival was 24.0 months and median progression-free survival was 13.4 months. Grade 3/4 neutropenia and thrombocytopenia occurred in 69.0 and 33.3% of patients, respectively, with no febrile neutropenia or hemorrhage. Grade 3/4 nausea and vomiting occurred in 35.7% and grade 3 alopecia in 21.4% of the patients. One patient died due to a toxicity-related death (dyspnea). CONCLUSIONS: Gemcitabine plus cisplatin is active and feasible as first-line treatment of advanced epithelial ovarian cancer. Further clinical trials adding gemcitabine to first-line treatment seem warranted.

Adult↗

PubMed2003

Validation of a new method of measuring esophageal acid exposure: comparison with 24-hour pH monitoring.

Recently, we developed a disposable acid exposure sensor whose in vitro response to acid below pH 4 is linearly determined by the duration of exposure and the degree of acidity. The aim of the present study was to compare the SR to simultaneous esophageal pH and duodenogastroesophageal reflux (DGER) monitoring (Bilitec) in patients investigated for presumed gastroesophageal reflux disease (GERD). Twenty-six patients (16 men, mean age 46 +/- 2 years) with symptoms suggestive of GERD underwent 24-hr ambulatory pH monitoring and SR monitoring at 5 cm proximal to the LES. DGER monitoring was performed in 21 patients. Exposure of the esophagus to acid and to DGER were analyzed. These data were compared to SR. A significant correlation was found between the exposure of the distal esophagus to acid and SR (R = 0.85; P < 0.0001). Similarly, the area below a cutoff pH 4 was significantly correlated to SR (r = 0.81; P < 0.0001). SR was not correlated to DGER (r = 0.16; NS). At a cutoff of 50, the sensitivity and specificity of SR to predict esophageal acid exposure > 5% of time were 91% and 93%, respectively conclusion, the response of the acid exposure sensor is strongly correlated with the results of simultaneous esophageal pH monitoring. The sensor seems able to reliably predict pathological esophageal acid exposure. These findings warrant larger studies of the clinical potential of the acid exposure sensor in the diagnosis and quantification of GERD.

Bile Reflux↗

PubMed2003

Effect of the GABA(B) agonist baclofen in patients with symptoms and duodeno-gastro-oesophageal reflux refractory to proton pump inhibitors.

BACKGROUND AND AIMS: A subset of patients with gastro-oesophageal reflux disease (GORD) with refractory symptoms during therapy with proton pump inhibitors (PPIs), have persistent non-acid duodeno-gastro-oesophageal reflux (duodenal reflux). The aim of the present study was to investigate the effect of the GABA(B) receptor agonist baclofen, which was shown to inhibit the occurrence of transient lower oesophageal sphincter relaxations (TLOSRs) in patients with persistent non-acid duodenal reflux during PPI therapy. METHODS: Patients were eligible for the study if they had persistent reflux symptoms, normal pH monitoring, and pathological Bilitec monitoring during PPI treatment. Upper gastrointestinal endoscopy and reflux symptom score were performed at the beginning of the study. Baclofen 5 mg three times daily was associated with treatment, and was increased by 5 mg every fourth day until a maintenance dose of 20 mg three times daily was reached. A reflux symptom questionnaire, ambulatory pH monitoring, and Bilitec monitoring were repeated four days later while PPI and baclofen were continued. All data are given as mean (SEM) or median (interquartile range) and were compared using the Student's t test or the Mann-Whitney U test. RESULTS: Sixteen patients (11 women, mean age 46 (3) years) with persistent heartburn or regurgitation for at least three months, in spite of PPI therapy, were included in the study. Erosive oesophagitis was present in seven patients (five with grade 1, two with grade 2). Under PPI therapy alone, all patients had normal acid exposure (0.3 (0.05; 2.2)% of the time) but pathological duodenal reflux exposure (13.8 (11.8; 15.5)% of the time). After addition of baclofen 20 mg three times daily, acid exposure was similar (0.4 (0.15; 2.3)% of the time; NS) but duodenal reflux had significantly decreased (6.1 (0.8; 10.3)% of the time; p<0.05). The number of duodenal reflux episodes and the number of longlasting duodenal reflux episodes (>5 minutes) was decreased, respectively, from 23 (14.5; 34) to 12 (5; 21) (p = 0.06) and from 5 (3; 8) to 2 (0.5;4.5) (p<0.05). The cumulative severity score for 14 reflux symptoms decreased from 10.3 (1.7) to 5.8 (1.3) (p<0.01). Four patients reported mild side effects of nausea or drowsiness. CONCLUSIONS: The GABA(B) receptor agonist baclofen improves duodenal reflux and associated reflux symptoms that persist during PPI therapy.

Adult↗

PubMed2003

Relevance of ineffective oesophageal motility during oesophageal acid clearance.

BACKGROUND: Oesophageal clearance of acid reflux consists of an initial volume clearance followed by neutralisation of the acidified mucosa by swallowed saliva (chemical clearance). Ineffective oesophageal motility (IOM), a frequent finding in patients with gastro-oesophageal reflux disease (GORD), has been claimed to underlie prolonged acid clearance by affecting oesophageal emptying and saliva transport. Intraluminal impedance allows non-radiological monitoring of movement of oesophageal liquids. AIMS: To evaluate the relevance of IOM during oesophageal volume and chemical clearance using combined pH impedance measurements. SUBJECTS: Impedance was validated with fluoroscopy to study volume clearance in three healthy subjects. Acid clearance tests were performed in 10 healthy subjects in the upright and supine positions, before and after oesophageal peristaltic disruption with sildenafil 50 mg. METHODS: After instillation of an acid bolus, simultaneous manometry, pH, and impedance were used to study oesophageal motility, chemical clearance, and volume clearance, respectively. RESULTS: Impedance allowed assessment of volume clearance accurately, showing a strong correlation with fluoroscopy (r(2)=0.89). Sildenafil provoked a graded impairment in oesophageal motility in healthy subjects without affecting saliva secretion. In the upright position, volume clearance was slightly prolonged only with severe IOM (>80% abnormal peristaltic sequences). In the supine position, severe IOM significantly prolonged chemical and volume clearance. Moderate IOM (30-80% abnormal peristalsis) had no effect. With normal peristalsis and moderate IOM, clearance times were similar in the upright and supine positions. Severe IOM however had a greater impact on clearance in the supine than in the upright position. CONCLUSION: Ineffective oesophageal motility has little effect on oesophageal clearance during upright acid reflux. With supine reflux, only severe IOM is associated with prolonged oesophageal clearance.

Acids↗

PubMed2003

Assessment of meal induced gastric accommodation by a satiety drinking test in health and in severe functional dyspepsia.

AIMS: Impaired gastric accommodation is a major pathophysiological mechanism in functional dyspepsia. The aim of the present work was to assess a satiety drinking test in the evaluation of accommodation in health and dyspepsia. METHODS: Twenty five controls and 37 severely dyspeptic patients seen at a tertiary care centre completed a dyspepsia questionnaire, and gastric emptying and gastric barostat studies. The amount of liquid meal ingested at maximum satiety during a slow satiety drinking test was determined. In controls, we studied the influence of caloric density and of pharmacological agents that influence accommodation. RESULTS: In patients, satiety scores were higher and maximum satiety occurred at lower calories (542 (50) v 1508 (53) kcal; p<0.0001). Six patients had required nutritional support, but excluding these did not alter the correlations. With increasing severity of early satiety, less calories were ingested at maximum satiety. In multivariate analysis, the amount of calories was significantly correlated to accommodation but not to gastric emptying or sensitivity. Sensitivity and specificity of the satiety test in predicting impaired accommodation reached 92% and 86%, respectively. At different caloric densities, ingested volume rather than caloric load determined maximum satiety. Pharmacological agents (sumatriptan, cisapride, erythromycin) affected the satiety test according to their effect on accommodation. CONCLUSION: A slow caloric drinking test can be used to evaluate accommodation and early satiety. It provides a non-invasive method of predicting impaired accommodation and quantifying pharmacological influences on accommodation.

Adult↗

PubMed2002

Calcium signalling and removal mechanisms in myenteric neurones.

To characterize further the Ca2+ signalling mechanisms of myenteric neurones, we studied the effect of thapsigargin, a blocker of the Ca2+-store ATPase, and the mechanisms involved in restoring the intracellular Ca2+ concentration ([Ca2+]i) after activation. Thapsigargin (5 x 10(-6) mol L(-1)) induced an oscillatory [Ca2+]i response in 86.6% of the neurones (n=276), which was blocked by the removal of extracellular Ca2+ and by omega-conotoxin MVIIA (5 x 10(-7) mol L(-1)). The IP3-blocker, 2-aminoethyl-diphenyl-borate (75 x 10(-6) mol L(-1)), blocked or reduced the responses in 74.5% of the neurones. The oscillatory responses induced by the depletion of Ca2+ stores suggest that myenteric neurones might recruite N-type Ca2+ channels as a refill mechanism. Thapsigargin pretreatment increased the amplitude, the upstroke and duration of the K+-induced [Ca2+]i responses. Mitochondrial blockers (rotenone and antimycin/oligomycin) also prolonged the responses, but without affecting the amplitude. Furthermore, it was found that for high [Ca2+]i, the thapsigargin-sensitive Ca2+ uptake was crucial, while mitochondrial blockade affected the Ca2+ uptake over a wide range of concentrations. The Ca2+-sequestering components might also have been compensating for each other, as most drugs only delayed and not inhibited Ca2+ removal.

Animals↗