The role of fat and cholecystokinin in functional dyspepsia

The main factors involved in the pathophysiology of fat induced dyspepsia were investigated by reviewing a series of controlled double blind randomised studies which sought to determine the role of nutrient fat and the postprandial release of cholecystokinin (CCK) in the development of dyspeptic symptoms in healthy volunteers and in patients with functional dyspepsia. The studies showed that during distension of the stomach, lipids are a major trigger of dyspeptic symptoms such as nausea, bloating, pain, and fullness, and that they modulate upper gastrointestinal sensations and symptoms in a dose related fashion. CCK is a major mediator of the sensitisation of gastric perception by lipids in patients with functional dyspepsia as the CCK-A receptor antagonist dexloxiglumide markedly diminishes this effect. The studies provide important insights into the mechanisms underlying gastrointestinal perception in response to fat and the role of CCK in patients with functional dyspepsia.     

Does Helicobacter pylori infection increase gastric sensitivity in functional dyspepsia?

The role of Helicobacter pylori infection in the pathogenesis of functional dyspepsia is debated. It is known that a substantial fraction of dyspeptic patients manifest a low discomfort threshold to gastric distension. This study investigated the symptomatic pattern in 27 H pylori positive and 23 H pylori negative patients with chronic functional dyspepsia, and potential relations between infection and gastric hyperalgesia. Specific symptoms (pain, nausea, vomiting, bloating/fullness, early satiety) were scored from 0 to 3 for severity and frequency (global symptom scores: 0-15). The mechanical and perceptive responses to gastric accommodation were evaluated with an electronic barostat that produced graded isobaric distensions from 0 to 20 mm Hg in 2 mm Hg steps up to 600 ml. Gastric compliance (volume/pressure relation) and perception (rating scale: 0-10) were quantified. Standard gastrointestinal manometry and recorded phasic pressure activity at eight separate sites during fasting and postprandially were also assessed. H pylori positive and H pylori negative patients manifested similar severity and frequency of specific symptoms and global symptom scores (mean (SEM)) (severity: 9.5 (2.0) v 9.0 (2.1); frequency: 10.8 (2.0) v 9.7 (2.2)). No differences were seen either in gastric compliance (53 (4) ml/mm Hg v 43 (3) ml/mm Hg) or in gastric perception of distension (slope: 0.50 (0.05) v 0.53 (0.06)). Postprandial antral motility was significantly decreased in H pylori positive patients (two hours motility index: 10.4 (0.6) v 12.6 (0.5); p < 0.05). It is concluded that H pylori infected patients with functional dyspepsia present no distinctive symptoms by comparison with H pylori negative counterparts and H pylori infection is associated with diminished postprandial antral motility but it does not increase perception of gastric distension.     

Symptoms and visceral perception in severe functional and organic dyspepsia

^a CURE: Digestive Disease Research Center/Neuroenteric Disease Program, UCLA, Los Angeles, California, USA, ^b Department of Medicine, Vanderbilt University, Nashville, Tennessee

Correspondence to: Dr E A Mayer, Neuroenteric Disease Program, West LA VA Medical Center, CURE Bldg 115, Rm 223, 11301 Wilshire Blvd, Los Angeles, California 90073, USA.

Accepted for publication 31 October 1997

Background—Hypersensitivity of gastric afferent pathways may play an aetiological role in symptoms of functional dyspepsia.
Aims—To determine whether patients with severe organic dyspepsia (associated with tissue irritation/injury) and those with functional dyspepsia (no detectable tissue irritation) differ in their perception of gastric distension and whether this difference is reflected in differences in their gastrointestinal and psychological symptoms.
Methods—Perceptual thresholds, referral patterns, and gastrointestinal and psychological symptoms were compared in 23 patients with functional dyspepsia, 10 organic dyspeptics, and 15 healthy controls.
Results—Fifteen (65%) functional dyspeptics and no organic dyspeptics had reduced perceptual thresholds for fullness, discomfort, or pain (odds ratio (OR) 19.56, 95% confidence interval (CI) 1.95 to 476.09, p=0.0017). Either reduced perceptual thresholds or altered referral was found in 20 (87%) functional dyspeptics and four (20%) organic dyspeptics (OR 10.0, 95% CI 1.34 to 89.54, p=0.014). During sham distension fullness, discomfort and pain were reported by healthy controls, organic dyspeptics, and functional dyspeptics. A sham response of pain but no other sensation was more frequent among functional dyspeptics (43%) than healthy controls (7%) (OR 10.77, 95% CI 1.10 to 257.35, p=0.026). Gastrointestinal and psychological symptoms and gastric compliance were similar in the functional and organic groups.
Conclusions—Alterations in the perception of gastric distension distinguishes between functional and organic dyspepsia, while symptoms do not. A total of 87% of functional dyspeptics studied had evidence of altered visceral afferent function. In this study population, psychological abnormalities or changes in compliance did not explain the findings.
(GUT 1998;:814-822)

Keywords: dyspepsia;  hyperalgesia;  visceral afferents

     

Visceral perception in health and functional dyspepsia

The symptoms of functional dyspepsia are still unexplained. To evaluate the possible role of abnormal visceral perception, we studied the symptomatic responses and the pressure variations during progressive gastric distension in 10 female healthy control subjects (mean age 33.6 years) and in 10 female patients with functional dyspepsia (mean age 35.2 years). A rubber balloon was positioned 4 cm below the lower esophageal sphincter (LES) and inflated with progressively larger volumes of air by steps of 50 ml; pressures at the gastric fundus and at the LES were continuously recorded by perfused manometric catheters. Each subject was studied on two separate occasions after randomized double-blind administration of either placebo or 20 mg of domperidone. Symptomatic responses and the manometric data were analyzed at the time of the initial recognition of distension (bloating step) and at the time of reporting pain or up to a maximum of 700 ml of balloon inflation (pain or 700-ml step). On placebo, the volumes of gastric distension were more than two times lower in patients than in control subjects at the bloating step (185±32 ml vs 470±40 ml,P=0.001) and at the pain or 700-ml step (265±54 ml vs 600±34 ml,P<0.005), while the pressure gradients (pressure at inflation steps minus baseline pressure before beginning inflation) were not statistically different between the two groups. On domperidone, the volumes at each of the two steps did not change in comparison to results on placebo except in healthy controls at the bloating step (470±40 ml on placebo vs 355±35 ml on domperidone,P<0.001); however, there was a trend for pressure gradients to increase on domperidone in comparison to results on placebo. We conclude that patients with functional dyspepsia have a lower threshold both to the initial symptomatic recognition and to perception of pain during gastric distension and that domperidone might have an effect on the threshold of these conscious visceral sensations. This increased visceral perception may alone or with other abnormalities of the gastroduodenal tract explain the symptoms of functional dyspepsia.This study was supported in part by a grant from Janssen Pharmaceutica Inc., Canada.     

Relations between upper abdominal symptoms and gastric distension abnormalities in dysmotility like functional dyspepsia and after vagotomy.

Postprandial bloating and fullness are commonly found both in dysmotility like functional dyspepsia, and after vagotomy but the relation between gastric accommodation and symptom production has not been investigated. Intragastric pressure levels and symptoms developed during controlled distension of the gastric fundus were recorded in nine patients with functional dyspepsia, in seven patients after truncal vagotomy, and in 11 healthy volunteers. The procedure was repeated after ingestion of a liquid nutrient meal (250 ml; 250 kcal). Gastric tone, expressed as the average value of pressure over the distension period was lower in controls (median: 11.3 mm Hg) than in either the dyspeptic patients (median: 16.48 mm Hg) or postvagotomy patients (median: 19.12 mm Hg) (p < 0.05). Meal ingestion reduced gastric tone in controls, but no significant change occurred in either the dyspepsia or the postvagotomy patients. Volumes at which discomfort was elicited by distension during fasting were lower both in dyspeptic patients (median: 210 ml) and in postvagotomy patients (median: 180 ml) than in healthy volunteers (median: 660 ml) (p < 0.05). Discomfort thresholds were unaffected by meal ingestion. These results suggest that a disturbance of gastric relaxation may be related to symptom development in dysmotility like functional dyspepsia, while similarities between dyspeptic patients and postvagotomy patients suggest that the impaired gastric accommodation in functional dyspepsia may be due to an underlying vagal defect.     

Role of autonomic dysfunction in patients with functional dyspepsia

BACKGROUND: The role of autonomic dysfunction in patients with functional dyspepsia is not completely understood. AIMS: 1. to prospectively assess abnormalities of autonomic function in patients with functional dyspepsia, 2. to assess whether autonomic dysfunction in these patients is associated with a. visceral hypersensitivity or b. delayed gastric emptying or c. severity of dyspeptic symptoms. PATIENTS: A series of 28 patients with functional dyspepsia and 14 healthy volunteers without gastrointestinal symptoms were studied. METHODS: All patients and controls were submitted to a battery of five standard cardiovascular autonomic reflex tests, dyspeptic questionnaire, gastric barostat tests and gastric emptying tests. RESULTS: 1. Autonomic function tests showed that both sympathetic and parasympathetic scores of dyspeptic patients were significantly higher than in controls; 2. visceral hypersensitivity was confirmed in dyspeptics in response to proximal gastric distension, demonstrating lower pain threshold; 3. delayed gastric emptying occurred more frequently in patients with functional dyspepsia than in controls; 4. epigastric pain and epigastric burning were significantly more prevalent in patients with definite evidence of autonomic dysfunction; 5. No significant association was found between presence of autonomic dysfunction and presence of visceral hypersensitivity or presence of delayed gastric emptying in patients with functional dyspepsia. CONCLUSIONS: We concluded that a possible role of autonomic dysfunction in eliciting dyspeptic symptoms could not be determined from alterations in visceral hypersensitivity or delayed gastric emptying. Autonomic dysfunction might not be the major explanation for symptoms associated with functional dyspepsia.     

Functional dyspepsia: recent pathophysiological advances

Functional dyspepsia is a clinical syndrome defined by upper abdominal symptoms, without identifiable cause by conventional diagnostic evaluation. New diagnostic tests, such as gastrointestinal manometry and gastric emptying, may help in a better characterization of these patients by demonstrating specific motor abnormalities, such as postprandial antral hypomotility and delayed gastric emptying of solids, or less frequently, intestinal dysmotility patterns indicating a visceral neuropathy. Nevertheless, a substantial proportion of dyspeptic patients have normal motility patterns. Interestingly, recent studies have shown that a gastric hypersensitivity to distension may be the cause of the postprandial symptoms in functional dyspepsia. These data indicate that functional dyspepsia may include an heterogeneous group of patients with different underlying disturbances.     

Effects of tropisetron, a 5-HT3 receptor antagonist, on proximal gastric motor and sensory function in nonulcer dyspepsia

BACKGROUND: Visceral hypersensitivity is claimed to be involved in the pathogenesis of nonulcer dyspepsia (NUD). In a double-blind crossover study, we evaluated the effects of tropisetron, a 5-HT3 receptor antagonist, on gastric accommodation, reflex relaxation, and sensitivity in NUD patients. METHODS: Eight patients and 10 healthy controls received placebo or 5 mg tropisetron on separate days. On each day, gastric accommodation and relaxation were investigated using a gastric barostat. The perception during gastric distension and relaxation was scored by a verbal perception score. RESULTS: Under both medications, gastric accommodation and postprandial gastric reflex relaxation were not impaired in the NUD patients. The visceral perception was increased in the NUD patients and not substantially influenced by tropisetron. CONCLUSIONS: Tropisetron does not influence gastric accommodation, reflex relaxation, or gastric sensitivity in NUD patients and healthy controls.     

Gallbladder contractility and volume characteristics in gallstone dyspepsia

AIM:It is difficult to differentiate gallstone dyspepsia and functional dyspepsia by clinical symptoms and signs. We hypothesized that gallstone dyspepsia was related to abnormal gallbladder motility. We aimed to differentiate gallstone dyspepsia from functional dyspepsia by measuring gallbladder motility.METHODS: We measured gallbladder volume changes in response to gastric distension (saline 500mL) and fatty meal in 10normal volunteers (controls) and 62 patients with gallstones and dyspepsia before cholecystectomy. Forty cholecystectomized patients were symptom free or had improvement (group I), while the remaining 22 patients had persistent dyspepsia (group Ⅱ). Gallbladder volume change and ejection fraction were analyzed and compared among the three groups.RESULTS:In group I, there were significant decreases in gallbladder volumes 5-25 rain after gastric distension,compared to fasting volumes. Compared to normal volunteers and group Ⅱ, group I had significantly decreased gallbladder volumes 10-20min after drinking 500mL of normal saline and 10 to 50min after eating fatty meal.CONCLUSION:Our results support the hypothesis that increased gallbladder contraction after gastric distension or fatty meal may be related to dyspeptic symptoms in uncomplicated gallstone disease. These findings may be useful in differentiating functional dyspepsia from gallstone dyspepsia, patients with the latter disease may benefit from laparoscopic cholecystectomy.     

Gastric perception thresholds are low and sensory neuropeptide levels high in helicobacter pylori-positive functional dyspepsia

BACKGROUND AND AIMS: In functional dyspepsia (FD) decreased perception levels can be shown on gastric distension. Substance P (SP) and calcitonin gene-related peptide (CGRP) are involved in the sensitization of afferent neuronal pathways due to chronic inflammation. The role of Helicobacter pylori-induced gastric mucosal inflammation in the pathogenesis of FD is controversial. The aim of this study was to assess whether FD patients have altered mucosal concentrations of CGRP and SP, and to investigate whether this is associated with visceral hypersensitivity or H. pylori infection. METHODS: Gastrointestinal symptoms, H. pylori status, perception thresholds at gastric balloon distension, and gastric mucosal concentrations of CGRP and SP were determined in 13 FD patients and 18 healthy controls (HC). RESULTS: In H. pylori-positive FD patients discomfort and pain thresholds on gastric distension were lower compared to other groups. Antral mucosal levels of CGRP and SP were higher in H. pylori-positive subjects. In FD significantly negative correlations between discomfort and pain thresholds and antral mucosal concentrations of CGRP and SP were observed. CONCLUSIONS: In FD low perception thresholds on gastric distension are associated with high levels of CGRP and SP in the antrum, suggesting that sensory neuropeptides are involved in FD pathophysiology.     

Relationship between antral distension and postprandial symptoms in functional dyspepsia

INTRODUCTION Patients with functional dyspepsia (FD)[1] complain of several gastrointestinal (GI) and extra-gastrointestinal (extra-GI) symptoms[2-5] that are usually associated with food ingestion[6]. Several pathophysiological abnormalities have been im…     

Effect of intranasal sumatriptan on gastric tone and sensitivity to distension

Sumatriptan is able to improve symptoms of early satiety in dyspeptic patients by relaxing the gastric fundus. The aim of this study was to verify the efficacy of intranasal administration of sumatriptan on gastric sensory motor function, in order to provide a new pharmacotherapeutic approach to functional dyspepsia. Thirteen healthy subjects were investigated twice on separate days. A gastric barostat was used to study the effect of placebo and sumatriptan, 20 mg intranasally, on basal fundic tone. In addition, stepwise isobaric distensions were performed and perception was measured before and after administration of drugs. Placebo had no effect on gastric tone and on perception. Sumatriptan caused a small, but short-lasting gastric relaxation and had no significant effect on sensitivity to distension and gastric compliance. Unlike the subcutaneous formulation, the intranasal administration of sumatriptan had no effect on gastric sensory motor functions, and this probably reflects a low biovailability of intranasally administered sumatriptan.     

Laser lithotripsy of difficult bile duct stones: results in 60 patients using a rhodamine 6G dye laser with optical stone tissue detection system

^a Department of Surgery, Utrecht University Hospital, Utrecht, The Netherlands, ^b Department of Gastroenterology

Correspondence to: Professor L M A Akkermans, Department of Experimental Surgery, Gastrointestinal Motility Unit, Utrecht University Hospital, PO Box 85500-3508 GA, Utrecht, The Netherlands.

Accepted for publication 18 December 1997

Background—Studies have shown that an altered visceral perception threshold plays a role in the pathogenesis of upper gastrointestinal tract symptoms in dyspeptic patients. However, it is not clear whether the compliance and adaptive relaxation of the proximal stomach contribute to the symptoms.
Aims—To investigate whether abnormal relaxation or adaptation of the proximal stomach during the interdigestive state and the postprandial phase could explain the symptoms of functional dyspepsia.
Subjects—Twelve volunteers and 12 patients with dysmotility-like functional dyspepsia were included in the study.
Methods—An electronic barostat was used to investigate adaptation to distension of the proximal stomach and accommodation in response to a liquid meal. Dyspeptic symptoms during distension and accommodation were assessed.
Results—When the subjects were in the fasting state, the pressure-volume curve showed slightly higher compliance in the dyspeptic patients (p<0.05). Patients not only had a higher score for nausea, bloating, and pain but also the increase in nausea and pain scores with intragastric pressure was higher than in volunteers (p<0.05). The increase in intragastric bag volume in response to a meal was significantly lower in patients (p<0.05). Both bloating and pain significantly increased in the patients (p<0.05), but not in the healthy volunteers.
Conclusions—Patients with functional dyspepsia show slightly higher compliance to mechanical distension. Their visceral perception of mechanical stress is enhanced. In contrast with the balloon distension, relaxation after a meal was less. Therefore the postprandial symptoms cannot be explained fully by greater global tension in the stomach wall, as assessed by the barostat technique. Visceral hypersensitivity plays a major role in the pathogenesis of the symptoms.
(GUT 1998;:823-829)

Keywords: dyspepsia;  gastric distension;  gastric accommodation;  gastric sensitivity

     

Pathophysiology of functional dyspepsia

Functional dyspepsia is a highly prevalent symptom complex and a heterogeneous disorder. Recent studies showed potential associations between specific pathophysiologic disturbances and dyspeptic symptoms. Delayed gastric emptying reported in about 30% of patients with functional dyspepsia is associated with the symptoms of postprandial fullness, nausea, and vomiting. Impaired gastric accommodation present in 40% of functional dyspepsia patients is found to be associated with early satiety. Hypersensitivity to gastric distension is observed in 37% of functional dyspepsia patients and associated with the symptoms of postprandial pain, belching, and weight loss. Psychosocial factors and altered response to duodenal lipids or acid have also been identified as pathophysiologic mechanisms.     

Effects of amitriptyline on gastric sensorimotor function and postprandial symptoms in healthy individuals: a randomized, double-blind, placebo-controlled trial

BACKGROUND:  Low-dose tricyclic antidepressants have been used to treat chronic somatic and gastrointestinal pain disorders, including refractory functional dyspepsia. However, there are only limited data on the effects of these drugs on upper gastrointestinal function.
AIM:  To compare the effects of two doses of amitriptyline (AMT) and placebo on gastric accommodation, emptying, satiation, and postprandial symptoms in healthy volunteers.
METHODS:  Using a parallel-group, double-blind, placebo-controlled design, 41 healthy volunteers were randomized to AMT 25 mg, AMT 50 mg, or placebo for 2 wk. During the final 3 days of therapy, the following end points were assessed: fasting and postprandial gastric volumes, 2- and 4-h gastric emptying, time and volume to maximum satiation using a nutrient drink test, and postprandial symptoms 30 min later using 10-cm visual analog scales. AMT and metabolite levels were measured.
RESULTS:  AMT slowed gastric emptying at 2 h (median 75% for placebo, 57% for AMT 25 mg, 67% for AMT 50 mg; P = 0.037) and 4 h (median 98% for placebo, 96% for AMT 25 mg, 92% for AMT 50 mg; P = 0.003). AMT did not affect gastric volumes or satiation volume, but it did reduce nausea scores at 30 min in a dose-dependent manner (median 2.1 for placebo, 0.9 for AMT 25 mg, and 0.0 for AMT 50 mg; P = 0.009).
CONCLUSION:  In healthy volunteers, AMT slows gastric emptying of solids, but it does not significantly affect gastric volumes or satiation. AMT reduces nausea after challenge with a high calorie liquid load.     

Effect of the 5-HT3 receptor antagonist, ondansetron, on gastric size in dyspeptic patients with impaired gastric accommodation

BACKGROUND: A reduction of gastric accommodation after a meal has been documented in patients with idiopathic dyspepsia. In these patients the administration of a 5-HT3 receptor antagonist may reduce some of the dyspeptic symptoms; it is not clear however, whether these drugs influence gastric adaptation to distension as well. AIM: To evaluate the effects of the 5-HT3 receptor antagonist, ondansetron, on gastric distension after a liquid meal in dyspeptic patients with reduced gastric accommodation. METHODS: Before and after a 500 ml water load, gastric accommodation (area of the proximal and distal stomach) was evaluated using real-time ultrasonography in 21 idiopathic dyspepsia patients and 26 healthy controls. In dyspeptic patients, the test was repeated twice: after the administration of placebo and after ondansetron 8 mg i.v. (in both cases, 15 min prior to the water load). Secondary outcomes were epigastric pain, fullness and nausea as assessed by a visual analogue scale at basal and after ondansetron. RESULTS: Fasting gastric size was similar in dyspeptic and controls. Compared with controls, dyspeptic patients showed a statistically significant smaller area of the proximal stomach (14.7+/-1.2 cm(2) vs. 18.6+/-1.4 cm(2), respectively; p=0.0247). In dyspeptic patients, gastric proximal and distal size did not change significantly following placebo, whereas after the administration of ondansetron the mean area of the proximal and distal stomach significantly increased (proximal stomach: 14.6+/-1.6 cm(2) placebo, 20.4+/-1.9 cm(2) ondansetron, p=0.0095; distal stomach: 8.9+/-0.9 placebo, 11.4+/-1.2cm(2) ondansetron, p=0.0409). Of the symptoms, only nausea was significantly reduced after ondansetron. CONCLUSION: In dyspeptic patients with impaired gastric accommodation, ondansetron reverts gastric accommodation to within the range of controls.     

Sleep and duodenal motor activity in patients with severe non-ulcer dyspepsia.

The prevalence of sleep disturbances was studied in patients with severe non-ulcer dyspepsia. It was also considered if the change in sleep pattern was associated with changes in the rhythmic fasting motor activity of the gastrointestinal tract, and if motor events correlate with the patient's symptoms. Motor activity in the duodenum was monitored over a 24 hour period under freely ambulatory conditions in 10 healthy controls and in 10 patients with severe non-ulcer dyspepsia using a transnasally placed catheter with six solid state pressure transducers connected to a digital data logging device. Symptoms and sleep disturbance were assessed by questionnaire and diary. Based on their symptoms, the patients were separated into two groups: those with dyspepsia symptoms only (non-ulcer dyspepsia; n = 5) and those with dyspepsia and additional functional symptoms thought to arise from the lower gastrointestinal tract (non-ulcer dyspepsia+irritable bowel syndrome; n = 5). When compared with either the control or the non-ulcer dyspepsia+irritable bowel syndrome group, non-ulcer dyspepsia patients had a considerably decreased number of migrating motor complexes during the nocturnal period (0.7 v 4.6), a decreased percentage of nocturnal phase I (5.2% v 78.0%), and an increased percentage of the nocturnal period in phase II (94% v 15.4%). Patients with non-ulcer dyspepsia+irritable bowel syndrome were not different from normal controls. Four of the non-ulcer dyspepsia patients and all of the non-ulcer dyspepsia+irritable bowel syndrome patients reported difficulties with sleep. Clusters of high amplitude tonic and phasic activity, not accompanied by subjective reports of discomfort were noted in several patients in both groups during the study. In eight of 10 patients, abdominal pain was reported during normal motor activity, while in one patient, pain correlated with phase III of the migrating motor complex. In contrast with previous reports in patients with irritable bowel syndrome, our findings suggest an abnormality of diurnal rhythmicity--shown in changed sleep and changed rhythmic duodenal motor activity--in patients with chronic abdominal pain thought to arise from the upper gastrointestinal tract.     

Absence of symptomatic benefit of lansoprazole, clarithromycin, and amoxicillin triple therapy in eradication of Helicobacter pylori positive, functional (nonulcer) dyspepsia

OBJECTIVES: The aim of this study was to compare the effect of a combination of lansoprazole, clarithromycin, and amoxicillin (LCA) versus placebo on the severity of symptoms in functional dyspepsia patients who were positive for Helicobacter pylori (H. pylori). METHODS: This was a double-blind, randomized, controlled clinical trial in adult patients with functional dyspepsia who were H. pylori positive. Patients were randomized to 7-day treatment with LCA or identical looking placebo. H. pylori status was confirmed by the urea breath test performed at baseline, at 6 wk, and at 6 and 12 months. The severity of eight upper GI symptoms was measured on a five-point Likert scale. The main outcomes were the change in average severity of the dyspepsia summary score of the eight symptoms and the proportion of patients who improved >/=4 points on the dyspepsia summary score. RESULTS: A total of 157 patients were included in the intention-to-treat analysis. LCA achieved cure of H. pylori infection in 82% of patients compared to 6% in the placebo group. The severity of dyspepsia symptoms improved over the 12-month study period, but for none of the outcome measures was there a significant difference between LCA and placebo. CONCLUSIONS: There was no difference in sustained improvement of dyspepsia symptoms when LCA was compared with placebo. An 82% cure rate of H. pylori infection was observed with LAC.     

Role of duodenal lipid and cholecystokinin A receptors in the pathophysiology of functional dyspepsia

BACKGROUND/AIMS: We aimed to evaluate the role of fat and cholecystokinin (CCK) in the pathophysiology of functional dyspepsia (FD) by investigating symptoms and plasma CCK levels following increasing doses of duodenal lipid during gastric distension, and the effect of CCK-A receptor blockade. SUBJECTS/METHODS: In study A, six FD patients were studied on three occasions during duodenal infusion of saline or lipid (1.1 (L-1) or 2 kcal/min (L-2)) and proximal gastric distensions. Six healthy subjects were also studied as controls during L-2 only. In study B, the effect of the CCK-A antagonist dexloxiglumide (5 mg/kg/h) on L-2 induced symptoms was studied in 12 FD patients. Changes in gastric volume at minimal distending pressure and plasma CCK (study A) were assessed, gastric distensions were performed using a barostat, and dyspeptic symptoms were monitored. RESULTS: Lipid increased gastric volume compared with saline (DeltaV (ml): saline 15 (20), L-1 122 (42), L-2 114 (28)) in patients and even more so in controls (221 (37); p<0.05). During distensions, symptoms were greater during L-2 than during saline or L-1, and greater in patients than in controls, while gastric compliance was smaller in patients than in controls (p<0.05). Lipid increased plasma CCK levels in patients and controls (p>0.05). Dexloxiglumide abolished the increase in gastric volume (DeltaV (ml): dexloxiglumide 17 (9), placebo 186 (49)) and dyspeptic symptoms (sum of scores: dexloxiglumide 24 (7), placebo 44 (19)) during duodenal lipid infusion. Dexloxiglumide also reduced gastric compliance (ml/mm Hg: dexloxiglumide 51 (7), placebo 72 (11)) and symptoms (sum of scores: dexloxiglumide 101 (17), placebo 154 (21)) during gastric distension. CONCLUSION: CCK-A receptors are involved in the generation of dyspeptic symptoms by duodenal lipid during gastric distension.     

Treatment of functional dyspepsia with a herbal preparation. A double-blind, randomized, placebo-controlled, multicenter trial

BACKGROUND: We aimed to assess the efficacy and safety of a herbal preparation STW 5-II containing extracts from bitter candy tuft, matricaria flower, peppermint leaves, caraway, licorice root and lemon balm for the treatment of patients with functional dyspepsia. METHODS: 120 patients with functional dyspepsia were randomly assigned to 1 of 4 treatment groups. Each patient received the treatment for three consecutive 4-week treatment blocks. The first two treatment blocks were fixed. For the third treatment period, medication was based upon the investigator's judgement of symptom improvement during the preceding treatment period. In patients without adequate control of symptoms, the treatment was switched, or if symptoms were controlled, the treatment was continued. The primary outcome measure was the improvement of a standardized gastrointestinal symptom score (GIS). FINDINGS: During the first 4 weeks, the GIS significantly decreased in subjects on active treatment compared to the placebo (p < 0.001). During the second 4-week period, symptoms further improved in subjects who continued on active treatment or who switched to the active treatment (p < 0.001), while symptoms deteriorated in subjects who switched to placebo. After 8 weeks 43.3% on active treatment and 3.3% on placebo reported complete relief of symptoms. (p < 0.001 vs. placebo). CONCLUSION: In patients with functional dyspepsia, the herbal preparation tested improved dyspeptic symptoms significantly better than placebo.