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Biomedical subjects

J Tack

Publications and source records attributed to J Tack.

At least 55 records · Page 3Linked to original sources
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↗
PubMed2005

Gastroesophageal reflux in patients with laryngeal disorders.

INTRODUCTION AND AIM: The aim of this study is to use anamnesis and laryngeal examination to investigate the occurrence of the gastroesophageal reflux disease GERD (with symptoms of regurgitation and heartburn, signs of oesophagitis, and pathological pH monitoring) among patients with suspected laryngopharyngeal reflux. MATERIALS AND METHODS: One hundred and sixty-nine patients with laryngopharyngeal reflux indicated by anamnesis and laryngeal examination were evaluated retrospectively with endoscopy and 24-hour double-probe pH monitoring. RESULTS: Combining endoscopy and pH monitoring made possible a diagnosis of GERD in 130 patients (77%). Of these patients, 58% had erosive oesophagitis and 84% had pathological oesophageal acid exposure. Of the patients with suspected laryngopharyngeal reflux and with established GERD, 49% reported gastrointestinal symptoms like heartburn or acid regurgitation. Erosive oesophagitis was confirmed in 45% of patients: grade 1 in 60 (35%), grade 2 in 10 patients (6%), and grades 3 and 4 in 3 patients each (2%). Distal oesophageal pH monitoring was pathological in 65% of patients. Of these, 93% had upright pathological acid exposure. Proximal oesophageal acid exposure was pathological in 39% of patients. CONCLUSIONS: Reflux can be suspected when a patient presents typical laryngeal symptoms and signs. The majority of these patients will not have typical GERD symptoms like heartburn, and endoscopic oesophagitis, mostly grade 1, is present in only a subset of patients with LPR. Oesophageal pH monitoring is the most appropriate test to demonstrate pathological oesophageal acid exposure.

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

Effects of capsaicin on the sensorimotor function of the proximal stomach in humans.

BACKGROUND: Capsaicin-sensitive afferents have been implicated in the control of visceral sensorimotor functions. AIM: To study the effects of capsaicin on the sensorimotor function of the proximal stomach in humans. METHODS: In 10 healthy subjects, a gastric barostat was used to study the effect of saline or capsaicin-containing red pepper sauce on the sensitivity to gastric distension and on gastric accommodation to a meal. RESULTS: The administration of capsaicin was accompanied by a relaxation of the proximal stomach. After capsaicin, the compliance of the proximal stomach was increased and higher perception scores were reached for the same distending pressures. Dosing with capsaicin significantly decreased the pressures and corresponding wall tensions at the discomfort threshold. Gastric accommodation to a meal was not altered by capsaicin. CONCLUSION: The acute administration of capsaicin decreases proximal gastric tone, inhibits phasic contractility of the proximal stomach and increases sensitivity to proximal gastric distension. These data suggest the involvement of vanilloid receptor 1 in the modulation of gastric sensorimotor function in humans.

Adult↗
PubMed2004

Development and psychometric evaluation of the patient assessment of upper gastrointestinal symptom severity index (PAGI-SYM) in patients with upper gastrointestinal disorders.

OBJECTIVE: Describe the development and evaluation of a new self-report instrument, the patient assessment of upper gastrointestinal disorders-symptom severity index (PAGI-SYM) in subjects with gastroesophageal reflux disease (GERD), dyspepsia, or gastroparesis. METHODS: Recruited subjects with GERD (n=810), dyspepsia (n = 767), or gastroparesis (n = 169) from the US, France, Germany, Italy, the Netherlands, and Poland. Subjects completed the PAGI-SYM, SF-36, a disease-specific HRQL measure (PAGI-QOL), and disability day questions. Two-week reproducibility was evaluated in 277 stable subjects. We evaluated construct validity by correlating subscale scores with SF-36, PAGI-QOL, disability days, and global symptom severity scores. RESULTS: The final 20-item PAGI-SYM has six subscales: heartburn/regurgitation, fullness/early satiety, nausea/vomiting, bloating, upper abdominal pain, and lower abdominal pain. Internal consistency reliability was good (alpha = 0.79-0.91); test-retest reliability was acceptable (Intraclass correlation coefficients alpha=0.60-0.82). PAGI-SYM subscale scores correlated significantly with SF-36 scores (all p < 0.0001), PAGI-QOL scores (all p < 0.0001), disability days (p < 0.0001), and global symptom severity (p < 0.0001). Mean PAGI-SYM scores varied significantly in groups defined by disability days (all p < 0.0001), where greater symptom severity was associated with more disability days. CONCLUSIONS: Results suggest the PAGI-SYM, a brief symptom severity instrument, has good reliability and evidence supporting construct validity in subjects with GERD, dyspepsia, or gastroparesis.

Analysis of Variance↗
PubMed2004

Visceral hypersensitivity in functional disorders of the upper gastrointestinal tract.

Visceral hypersensitivity is now recognised as a major pathophysiological mechanism in functional gastrointestinal disorders of the upper gastrointestinal tract. In patients with non-cardiac chest pain and functional dyspepsia, a high prevalence of visceral hypersensitivity has been indeed observed. In these patients, luminal physiological stimuli can be perceived as unpleasant or even painful. Although the fine mechanisms underlying such "aberrant perceptions" are yet not fully clarified, it is thought that an altered activation of the gut-wall receptors, an altered conduction of sensory inputs at the level of neural pathways, or an impaired processing of the sensations at the level of brain, may occur along the brain-gut axis. So far, drugs able to reduce hypersensitivity, that target each of the constituents of the stimuli-perception chain, have the therapeutic potential to reduce visceral hypersensitivity and, thus, to improve the symptoms. In this context, the availability of new agonists/antagonists to neurotransmitters offers a new exciting tool for the treatment of functional disorders of the upper gastrointestinal tract.

Chest Pain↗
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

Review article: approaches to endoscopic-negative reflux disease: part of the GERD spectrum or a unique acid-related disorder?

Endoscopic-negative reflux disease (ENRD) is the most common presentation of gastro-oesophageal reflux disease (GERD)-affecting up to 70% of these individuals. In the last three decades therapeutic studies have focused solely on the treatment of patients with erosive oesophagitis. However, more recent studies have shifted our attention to defining, understanding and treating those with ENRD. GERD has traditionally been approached as a spectrum with ENRD at the mild end and complicated GERD (i.e. patients with erosive oesophagitis, stricture and Barrett's oesophagus) being at the other end, suggesting that patients' disease may progress over time along the spectrum. Current data indicate that ENRD should be approached as a unique entity rather than a part of the GERD spectrum and that over time only a few patients with ENRD will develop GERD-related complications. Patients with ENRD are a heterogenous group of patients with different aetiologies for their heartburn symptoms, including motor events, reflux of acidic or nonacidic gastric contents, minute changes in intraesophageal pH (pH < 4), mucosal hypersensitivity, and emotional or psychological abnormalities. By dropping the spectrum concept, which emphasizes oesophageal mucosal injury, we can focus our attention on the specific mechanisms that lead to symptom generation in each of the three unique groups of GERD (ENRD, erosive oesophagitis and Barrett's oesophagus) and on the specific therapeutic modalities that benefit each of these individual groups. Acid suppressive therapy with proton pump inhibitors is highly effective in healing erosions and controlling symptoms in those with erosive oesophagitis. In those with ENRD the resolution or control of heartburn with proton pump inhibitor therapy is greater than that with placebo or H2 receptor antagonist, but not as consistent nor as impressive as the results observed in studies of patients with erosive oesophagitis. By considering the mechanisms involved in ENRD symptom generation, future studies that include high-dose proton pump inhibitors, promotility agents (alone or in combination with proton pump inhibitors), transient lower oesophageal sphincter reducers, or pain modulators (e.g. tricyclic antidepressant agents) may prove beneficial.

Endoscopy, Gastrointestinal↗
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

Calcium imaging of gut activity.

The major cell types regulating gut motility include enteric neurones, interstitial cells of Cajal (ICC) and their effector smooth muscle cells. These cells are arranged conveniently in nested layers through the gut wall. Our knowledge of how many of these cells in each layer are integrated to produce the various patterns of motility is largely unknown. So far, much of our knowledge of gut motility has usually been obtained by examining point sources of activity (e.g. intracellular recordings from enteric neurones, ICC and smooth muscle cells), rather than the spread of activity through these spatially distributed nerve and ICC networks, or smooth muscle syncitia. Our understanding of how these cells are integrated to produce gut movements would be greatly enhanced if we could image the activity in many of these cells in each layer, or many cells in several layers, simultaneously. Calcium (Ca2+) is a major signalling and regulatory molecule in most cells. In fact, electrical excitability in enteric neurones, ICC and smooth muscle is associated with robust rises in intracellular Ca2+ that long outlast the electrical events (e.g. action potentials in neurones and smooth muscle) that gave rise to them. These prolonged Ca2+ responses, together with the development of several high quality Ca2+ indicators, has provided a unique opportunity to image many cells in intact tissues simultaneously using ICCD video-rate cameras along with conventional microscopy. However, confocal microscopy has also been used, and has several advantages over the above systems. These include reduced photo-toxicity and bleaching and the elimination of out of focus light from different layers within the tissue. So far, despite some limitations with the calcium imaging techniques, the spread of activity through the two layers of smooth muscle, ICC networks and myenteric neurones in intact preparations, or cultured myenteric neuronal networks, is beginning to yield exciting new data about how these different cells interact and process information.

Animals↗
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

The role of tension receptors in colonic mechanosensitivity in humans.

BACKGROUND: Perception of colonic distension, which is enhanced in a subset of patients with irritable bowel syndrome, requires activation of mechanoreceptors. In animal studies, distension activates both in series ("tension") and in parallel ("elongation") mechanoreceptors. During active contractions against a fixed volume balloon, tension receptors are activated without elongation of receptor activation. AIM: To evaluate the role of tension receptors in the perception of mechanical stimuli from the colon in healthy subjects. METHODS: A 700 ml balloon connected to a barostat-manometer assembly was placed in the descending colon of 10 healthy subjects. After volume controlled distension (50 ml/2 minutes) to assess the first perception threshold, fixed volume subthreshold distension (122 (16) ml) was maintained for a 30 minute period before and after administration of neostigmine 0.5 mg intravenously. Mean intraballoon pressure, number, amplitude, and duration of contractions, and frequency of sensations were analysed. The period after neostigmine was divided into 10 second intervals and evaluated for the occurrence of contractions and onset of sensations. Fisher's exact test was applied to calculate the sensation-contraction association probability (SAP) as (1.0-p)x100%. RESULTS: Neostigmine increased intraballoon pressure (p<0.01), number of contractions (p<0.01), and number of sensations (p<0.01) per minute in all subjects. In seven of 10 subjects a significant association (SAP >95%) was found between sensations and contractions. In the remaining subjects, contractions were not associated with sensations and had lower amplitude (p<0.05) and duration (p<0.01) compared with contractions in the other seven subjects. CONCLUSION: In humans, tension receptors are involved in mediating colonic mechanosensitivity.

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

Clinical trial guidelines for pharmacological treatment of irritable bowel syndrome.

Appropriate guidelines for clinical trials in irritable bowel syndrome are needed because of the inadequacy of previously performed trials, the use of new and more adequate patient definition, new emerging pathophysiological models and the unique requirements related to the assessment of treatment outcome that, in the absence of a biological marker, can rely only on the evaluation of clinical manifestations. This consensus report highlights the following points. (a) A 4-week period is considered to be adequate to assess drug efficacy for the control of symptoms. (b) For the cyclic and non-life-threatening nature of the disease, a long-term study of 4-6 months or more of active treatment to establish efficacy is considered to be inappropriate in the large majority of patients. (c) In the initial assessment phase of drug efficacy, the withdrawal effect of treatment can be ascertained during a follow-up period prolonged for a sufficient time (4-8 weeks) after stopping treatment. Subsequent trials with proper withdrawal phase design and duration can then ascertain the drug post-treatment benefit. (d) Considering the intermittent clinical manifestations of irritable bowel syndrome, designing trials with on-demand or repeated cycles of treatment could be envisaged. However, the lack of a definition of what constitutes an exacerbation is a major obstacle to the design of such trials. In the absence of an established gold standard, appropriately justified novel trial designs are welcome. (e) Patients eligible for inclusion should comply with the Rome II diagnostic criteria for irritable bowel syndrome. (f) The main efficacy outcome of the treatment should be based on one primary end-point. (g) The primary efficacy end-point could combine, in a global assessment, the key symptoms (abdominal pain, abdominal discomfort, bowel alterations) of irritable bowel syndrome or rate any single symptom for drugs considered to target specific symptoms. (h) A 50% improvement in the primary efficacy end-point seems to be a reasonable definition of a responder.

Clinical Trials as Topic↗
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↗