Symptoms and Pathophysiological Correlations in Patients with Constipation and Functional Dyspepsia

os

tdpaeHgd

scmtlcpoeetp

aisstofii4mpgp

bts

Fsticmp

T

D

D

1240 TACK ET AL. GASTROENTEROLOGY Vol. 127, No. 4

ccurs between 45 and 90 minutes after ingestion of atandardized 250-kcal meal.18,19

Weight loss is traditionally considered an alarm symp-om, pointing toward diagnoses other than functionalyspepsia. Recent studies in tertiary care patients re-orted the presence of weight loss as a symptom associ-ted with functional dyspepsia,8–11 but this was consid-red to reflect the situation in tertiary care only.owever, more recent, preliminary observations in the

eneral population also report an association betweenyspeptic symptoms and weight loss.13

Pathophysiologic Mechanisms andTheir Relation to Symptom Pattern

Several pathophysiologic mechanisms have beenuggested to underlie dyspeptic symptoms. These in-lude delayed gastric emptying, impaired gastric accom-odation to a meal, hypersensitivity to gastric disten-

ion, H. pylori infection, altered response to duodenalipids or acid, abnormal duodenojejunal motility, orentral nervous system dysfunction (Figure 2). Atresent, the pathophysiology of functional dyspepsia isnly partially elucidated. However, there is growingvidence that functional dyspepsia is in fact a very het-rogeneous disorder and different subgroups can be iden-ified based on different demographic, clinical, andathophysiologic features.7–11

able 1. Definition of Functional Dyspepsia and SubgroupsAccording to the Rome II Working Committee5

efinition of functional dyspepsia, according to the Rome II workingteam:

At least 12 weeks (which need not be consecutive), within thepreceding 12 months, of the following:

Persistent or recurrent pain or discomfort centered in theupper abdomen;

No evidence of organic disease (including upper endoscopy)that is likely to explain the symptoms; and

No evidence that the dyspepsia is exclusively relieved bydefecation or associated with the onset of a change in stoolfrequency or stool form (i.e., not irritable bowel syndrome)

yspepsia subgroups based on the predominant or mostbothersome symptoms, according to the Rome II workingteam:

Ulcer-like dyspepsiaPain centered in the upper abdomen is the predominant (most

bothersome) symptomDysmotility-like dyspepsia

An unpleasant or troublesome nonpainful sensation(discomfort) centerd in the upper abdomen is thepredominant symptom; this sensation may be characterizedby or associated with upper abdominal fullness, earlysatiety, bloating, belching, or nausea

Unspecified dyspepsiaCannot be classified as above

Delayed Gastric Emptying

Delayed gastric emptying is traditionally consideredmajor pathophysiologic mechanism underlying symptoms

n functional dyspepsia and idiopathic gastropare-is.7,11,20–29 Several studies have investigated the relation-hip between delayed gastric emptying and symptom pat-ern and severity. Depending on the study, the percentagef dyspeptic patients with delayed gastric emptying rangesrom 20% to 50%.7,11,20–29 In a meta-analysis of 17 studiesnvolving 868 dyspeptic patients and 397 controls, signif-cant delay of solid gastric emptying was present in almost0% of patients with functional dyspepsia.23 However,ost of the studies were performed in small groups of

atients and small control groups. In the largest studies,astric emptying of solids was delayed in about 30% of theatients with functional dyspepsia.7,11,27–29

Most studies failed to find a convincing relationshipetween delayed gastric emptying and symptom pat-ern.20–22 More recently, 3 large-scale single-center studieshowed that patients with delayed gastric emptying for

igure 1. Symptom pattern in patients with functional dyspepsiaeen at a tertiary referral center. (A) Percentage of dyspeptic symp-oms rated as moderate or severe (scores 2 and 3 on a scale of 0–3)n 640 patients with functional dyspepsia seen at a tertiary referralenter. (B) Prevalence of the number of symptoms that are rated asoderate or severe (scores 2 and 3 on a scale of 0–3) in 640atients with functional dyspepsia seen at a tertiary referral center.

saffsf

srstaciv

awitCrpmiit

ptie

gemgetppth

pimatcmtdhaTdiubbi

Fp

T

WJTWKSS

MP

S

T

October 2004 FUNCTIONAL DYSPEPSIA 1241

olids are more likely to report postprandial fullness, nausea,nd vomiting,7,11,28 although a large multicenter studyailed to find any association29 (Table 2). Almost all studiesocused on solid emptying rate only. A recent large-scaletudy suggested an association between delayed emptyingor liquids and symptoms of postprandial fullness.11

Impaired Gastric Accommodation to a Meal

The motor functions of the proximal and distaltomach differ remarkably. Whereas the distal stomachegulates gastric emptying of solids by grinding andieving the content until the particles are small enougho pass the pylorus, the proximal stomach serves mainlys a reservoir. Accommodation of the stomach to a mealonsists of a relaxation of the proximal stomach, provid-ng the meal with a reservoir and enabling an increase inolume without an increase in pressure.

Scintigraphic and ultrasonographic studies have shownn abnormal intragastric distribution of food in patientsith functional dyspepsia, with preferential accumulation

n the distal stomach.22,30–33 These findings suggest defec-ive postprandial accommodation of the proximal stomach.onsistently, studies using a gastric barostat have shown

educed proximal gastric relaxation in response to a meal inatients with functional dyspepsia.8,34 Insufficient accom-odation of the proximal stomach during and after the

ngestion of a meal may be accompanied by increasedntragastric pressure and activation of mechanoreceptors inhe gastric wall, thus inducing symptoms.

Using a gastric barostat in 40 consecutive dyspepticatients, we showed that impaired gastric accommoda-ion was present in 40% of the patients and that thismpairment was associated with symptoms of early sati-ty and weight loss.8 The relation between impaired

igure 2. Normal fasting and postprandial gastric function; patho-hysiologic mechanisms putatively involved in functional dyspepsia.

astric accommodation and early satiety was also appar-nt from the correlation between the amplitude of theeal-induced relaxation and the amount of calories in-

ested at maximum satiety in patients with early sati-ty.8 Others, using single-photon emission computedomography, scintigraphy, or barostat studies of theroximal stomach, have confirmed the prevalence of im-aired accommodation in approximately 40% of dyspep-ic patients, but the relationship with symptom patternas been found to be less consistent (Table 3).35–37

An unsolved issue is the site of symptom generation inatients with impaired accommodation. When the prox-mal stomach is not relaxing properly, ingestion of aeal may be accompanied by activation of tension mech-

noreceptors in the proximal stomach wall and genera-ion of symptoms. On the other hand, insufficient ac-ommodation of the proximal stomach may force theeal into the distal stomach, thereby creating a dis-

ended antrum. Studies on the induction of symptomsuring proximal and distal gastric distention in humansave shown conflicting results38–40 that are at least partlyttributable to technical and methodological differences.he gold standard for assessment of gastric sensitivity toistentions is currently the gastric barostat; however,nstead of dual barostat distentions, these studies usedltrasound measurements or single water-filled orarostat balloons. In a recent study using a double gastricarostat assembly, we showed that symptom profilesnduced by gastric distention did not differ between

able 2. Prevalence of Delayed Emptying and RelationshipWith Symptoms in Functional Dyspepsia inLiterature Studies

Study n

Prevalenceof delayedemptying

(%) Correlation

egener et al., 198920 43 30 No correlationian et al., 198921 28 59 No correlationalley et al., 198922 32 30 No correlationaldron et al., 199123 50 42 No correlationlauser et al., 199324 69 35 No correlationcott et al., 199325 75 28 No correlationtanghellini et al.,19967

343 34 Associated with femalesex, postprandialfullness, vomiting

aes et al., 199727 344 30 Not studiederri et al., 199828 304 33 Associated with

postprandialfullness, nausea,and vomiting

arnelli et al., 200311 392 23 Associated withpostprandialfullness, nausea,and vomiting

alley et al., 200129 551 24 No correlation

prHtpu

amitttgsttn

ppdsgpst

ohtsciaicd

cfimt

tpbmgpntgstprpddpnTmut

T

TK

BP

a

T

MRT

B


roximal and distal gastric distention and that mechano-eceptors from both sites may contribute to symptoms.41

owever, because the distal gastric wall is less complianthan the proximal gastric wall, the distal stomach mayroduce greater symptoms in response to the same vol-me of distention.41

Hypersensitivity to Gastric Distention

Physiologic stimuli during the digestive processre not normally perceived but in some circumstancesay induce conscious sensations. During the past decade,

t has been suggested that patients with functional gas-rointestinal diseases may have a sensory dysfunction ofhe gut, so that physiologic stimuli would induce symp-oms.42 Several studies have clearly established that, as aroup, patients with functional dyspepsia have enhancedensitivity to gastric distention.9,36,43–46 However, inhese studies, different approaches to calculate sensitivityo gastric distention and to determine the range oformality have been used.A systematic analysis in a large group of controls and

atients indicated that the increase in the intra-balloonressure over intra-abdominal pressure needed to induceiscomfort or pain is the most appropriate expression ofensitivity to gastric distention.9 According to that study,astric hypersensitivity was associated with symptoms ofostprandial pain, belching, and weight loss. So far, other,maller-scale studies have failed to find an association be-ween hypersensitivity and symptom pattern (Table 4).36,47

Perception of gastric distention requires the activationf mechanoreceptors, and studies in healthy volunteersave suggested involvement of “in series” mechanorecep-ors that respond to increases in tension within thetomach wall.48,49 By analyzing the relationship betweenhanges in perception and increases in pressure in ansovolumetric balloon in the proximal stomach, we wereble to show that dyspeptic patients with hypersensitiv-ty to gastric distention perceive isovolumetric phasicontractions of the proximal stomach.50 Fundus-relaxingrugs decrease sensitivity to gastric distention and de-

able 3. Prevalence of Impaired Accommodation and RelatioStudies

Study n Technique

ack et al., 19988 40 Barostatim et al., 200135 32 Single-photon emissio

tomographyoeckxstaens et al., 200236 44 Barostatiessevaux et al., 200337 40 Scintigraphy

The symptom of early satiety was not assessed in this study.

rease meal-induced symptoms in these patients.50 Thesendings are compatible with involvement of tensionechanoreceptors in the symptom generation in dyspep-

ic patients with visceral hypersensitivity.Because patients with hypersensitivity to gastric dis-

ention have more prevalent symptoms of epigastricain9,17 and because they experience pain during gastricalloon distention at levels of distention that are nor-ally not painful, these patients have visceral hyperal-

esia.43–45 According to the neurophysiologic theory ofain, pain can be encoded by activation of high-thresholdociceptive pathways or by intense stimulation of low-hreshold multimodal pathways.51 To determine whetherastric hypersensitivity in functional dyspepsia reflects aelective sensitization for painful sensations or whetherhe sensitivity for nonpainful stimuli is also enhanced inatients with visceral hypersensitivity, we analyzed theelationship between intensity scores for pain and non-ainful sensations during gastric balloon distention inyspepsia.52 In both normosensitive and hypersensitiveyspeptic patients, the elevation of intensity scores forain paralleled the elevation of intensity scores for theonpainful sensations of nausea, satiety, and fullness.hese findings are compatible with up-regulation ofultimodal afferent pathways and argue against isolated

p-regulation of pain-specific afferent pathways in func-ional dyspepsia with visceral hyperalgesia.

With Symptoms in Functional Dyspepsia in Literature

Prevalence ofimpaired

accommodation (%) Correlation

40 Early satiety, weight lossmputed 40 Weight lossa

40 No correlation50 Early satiety

able 4. Prevalence of Hypersensitivity to Gastric Distentionand Relationship With Symptoms in FunctionalDyspepsia in Literature Studies

Study n

Prevalence ofhypersensitivity

(%) Correlation

ertz et al., 199846 24 66 No correlationhee et al., 200047 64 50 No correlationack et al., 20019 160 34 Pain, belching,

weight lossoeckxstaens et al.,200236

44 48 No correlation

nship

n co

bdstfm

rrfrotttea

tpsvtdptbcs

chna

trctatiers(tsai

itdsaraewatnpsbtr

sita

T

B

B

S

F


Dyspeptic symptoms are usually triggered or aggravatedy meal ingestion, suggesting that sensitivity to gastricistention in the postprandial period might be involved inymptom generation. In a preliminary study, we showedhat postprandial sensitivity to gastric distention, but notasting sensitivity, was indeed related to the severity ofeal-related symptoms in functional dyspepsia.53

H. pylori Infection

Soon after the discovery of H. pylori, a causalelationship between H. pylori infection and the occur-ence of duodenal and gastric ulcers was established.51 Inunctional dyspepsia, the role of H. pylori is less clear. Aecent systematic review of the epidemiologic evidencen a relationship between H. pylori infection and func-ional dyspepsia found no evidence for a strong associa-ion. However, according to the investigators, many ofhe studies had important weaknesses in design andxecution and there was not enough evidence to rule outmodest association.55

Several studies have investigated the association be-ween H. pylori infection and dyspeptic symptoms orathophysiologic mechanisms.28,56–61 However, no con-istent differences in the prevalence and severity of indi-idual dyspeptic symptoms, gastric emptying rate, gas-ric relaxation after a meal, and sensitivity to gastricistention were found between H. pylori–positive and H.ylori–negative subjects. Initial studies reported associa-ions between H. pylori infection and epigastric pain orurning,56 delayed gastric emptying,57 or impaired ac-ommodation.58 However, more recent and larger-scaletudies failed to find any of these correlations.59–61

Altered Duodenal Sensitivity to Lipids orAcid

Dyspeptic symptoms in functional dyspepsia areommonly exacerbated by meals rich in fat.62 Studies inealth have shown that duodenal infusion of lipids, butot glucose, induces a relaxation of the proximal stomachnd enhances the sensitivity to proximal stomach disten-

able 5. Literature Studies on Duodenal Hypersensitivity in F

Study n Techniqu

arbera et al., 199568 10 patients10 controls

Duodenal lipid infusion,infusion, gastric ballo

arbera et al., 199567 9 patients9 controls

Duodenal lipid infusion,glucose infusion, gastdistention

amsom et al., 199971 12 patients10 controls

Duodenal acid infusion,manometry and pH m

einle et al., 200166 12 patients Duodenal lipid infusion,distention, CCK-A anta

CCK, cholecystokinin.

ion.63,64 These influences of duodenal lipid infusionequire lipid digestion and subsequent release of chole-ystokinin,64,65 and they can be blocked by administra-ion of a lipase inhibitor or a cholecystokinin-A receptorntagonist.64–66 It was reported that increased sensitivityo duodenal lipid infusion may be a relevant pathophys-ologic mechanism in functional dyspepsia.67,68 How-ver, the numbers of patients studied in this manneremained small, and it is unclear whether this affects aubgroup of dyspeptic patients or all dyspeptic patientsTable 5). Furthermore, all of these studies used in-raduodenal mode administration, and recent data havehown that observations derived from intraduodenallydministered lipids do not necessarily apply to orallyngested lipid-containing meals.69,70

Duodenal infusion of hydrochloric acid was found tonduce nausea in a small group of patients with func-ional dyspepsia but not in healthy controls, suggestinguodenal hypersensitivity to acid. Furthermore, previoustudies have shown that the duodenal motor response tocid was decreased in patients with functional dyspepsia,esulting in reduced clearance of exogenous duodenalcid.71 We confirmed that spontaneous duodenal acidxposure to endogenous acid was increased in patientsith functional dyspepsia who displayed delayed clear-

nce of exogenous duodenal acid.72 Patients with func-ional dyspepsia with duodenal acid exposure above theormal range had higher severity scores of several dys-eptic symptoms. However, the severity of individualymptoms was weakly correlated to duodenal pH andrief duodenal acid infusion did not affect any symp-oms, suggesting that duodenal acid exposure is poorlyelated to symptom severity.72

Altered Antroduodenojejunal Motility

Manometry studies in functional dyspepsia havehown antral hypomotility to be a common feature.73 Its presently unclear whether this reflects true hypomo-ility or a poor registration of contractions in a dilatedntrum in patients with impaired accommodation, be-

ional Dyspepsia

Conclusion

enal salinestention

Duodenal lipids sensitize the stomach to distentionin patients with dyspepsia but not in controls

enallloon

Duodenal lipids but not glucose sensitize thestomach to distention in dyspepsia

enalring

Acid clearance is decreased in dyspepsia;hypersensitivity to duodenal acid induces nausea

ic balloonst

CCK-A receptors are involved in sensitization byduodenal lipids

unct

e

duodon diduodric ba

duodonitogastrgoni

cthiht

uctrtwprib

ssipbtttsuft(pPpaobcf

tpes

aadfadb

towswfpnaawuh

rscbAtibai

tuatsdtttrre


ause manometry only registers lumen-obliterating con-ractions.8,30–32,73 Small bowel motor alterations, usuallyypermotility with burst activity or clusters, and anncreased proportion of duodenal retrograde contractionsave been reported.74,75 No clear correlation with symp-oms has been found.74,75

Abnormalities of Gastric Electrical Rhythm

There is also evidence that abnormalities in thenderlying gastric myoelectrical activity, as measured byutaneous electrogastrography, are found in up to twohirds of patients with functional dyspepsia.76,77 Theelevance of this finding for gastric emptying and symp-om patterns remains to be established. No correlationas found between dyspeptic symptom pattern and theresence of findings on electrogastrography. A good cor-elation between the presence of delayed gastric empty-ng and abnormalities of gastric electrical rhythm haseen reported.76,77

Unsuppressed Postprandial PhasicContractility in the Proximal Stomach

Besides the relaxatory response of the proximaltomach after a meal, other motor aspects of the proximaltomach have not been particularly frequently addressedn the literature. With the barostat technique, it is alsoossible to detect phasic volume fluctuations from theaseline volumes (“volume waves”), reflecting contrac-ions superimposed on the background state of contrac-ility or tone.78 These contractions occur at a frequencyhat differs from antral contraction waves.59,78,79 Onetudy suggested the occurrence of increased phasic vol-me events in the postprandial period in patients withunctional dyspepsia.59 In a recent study, we observedhat, compared with healthy controls, a small subset15%) of dyspeptic patients displayed unsuppressed post-randial phasic contractility of the proximal stomach.79

ersistence of postprandial phasic contractions of theroximal stomach was associated with H. pylori infectionnd relevant or severe bloating, but also with the absencef nausea. The abnormality is of potential relevanceecause phasic fundic contractions induce transient in-reases in gastric wall tension, which can be perceived inunctional dyspepsia.50

Autonomic Nervous System/CentralNervous System Dysregulation

Abnormalities within the autonomic nervous sys-em have been suggested to be of importance in someatients with functional dyspepsia. More specifically, anfferent vagal dysfunction has been observed in severaltudies80,81 and has been proposed to be a possible mech-

nism underlying impaired accommodation to a meal82

nd antral hypomotility.80 Furthermore, there is evi-ence of an association between psychopathology andunctional dyspepsia83 and between psychological factorsnd gastric functioning and symptoms in functionalyspepsia, for which low vagal activity was proposed toe the mediating mechanism.84,85

In a recent factor analysis of dyspeptic symptoms andheir relationship with physiopathology and psychopathol-gy, the heterogeneity and complexity of these interactionsas clearly shown. Factor analysis identified 4 separate

ymptom factors within functional dyspepsia, each of whichas associated with a measurable abnormality of gastric

unction, and of which 2 were associated with specificsychosocial characteristics.17 The factor that consists ofausea, vomiting, early satiety, and weight loss was associ-ted with female sex and physician visits and sickness leave,nd the factor that consists of epigastric pain was associatedith several psychosocial dimensions, including medicallynexplained symptoms and conditions, and with lowealth-related quality of life.17

Relevance of PutativePathophysiologic Mechanisms toSymptom Generation

Although several pathophysiologic abnormalities areelated to the dyspepsia symptom pattern and severity, asummarized in the previous section, this does not establishausality. It is conceivable that both simply coexist or thatoth depend on a presently unspecified causal mechanism.close correlation between presence and severity of a cer-

ain pathophysiologic abnormality and presence and sever-ty of certain symptoms adds strength to the associationetween both. A very strong case is made when induction ofpathophysiologic abnormality in healthy subjects also

nduces dyspeptic symptoms.

Delayed Gastric Emptying

The studies investigating the relationship be-ween delayed emptying and symptom pattern generallysed questionnaires that assessed symptom severity overtime frame of weeks to months, whereas the emptying

est reflects the situation at a single point in time. Severaltudies have shown that gastric emptying in functionalyspepsia has large intraindividual variability.19,86 At-empts have been made to find a better correlation be-ween symptoms and emptying rate by assessing symp-om severity during the measurement of the emptyingate of a standardized meal.18,19 However, this did notesult in a better correlation between symptoms andmptying rate.

hite

gadmatmadrnnmshn

stHbappsiiitt

tewsD

a

svospre

patmistuiptp

sbottao

T

DHIHDDUA


Furthermore, induction of delayed gastric emptying inealthy subjects by pharmacologic or dietary interventionss not associated with the occurrence of dyspeptic symp-oms.87 These observations question the relevance of delayedmptying as a mechanism underlying dyspeptic symptoms.

Impaired Accommodation

A close correlation exists between impairment ofastric accommodation, severity of early satiety, and themount of liquid meal ingested at maximum satietyuring a slow satiety drinking test.88 Erythromycin andotilin induce a contraction of the proximal stom-

ch.89,90 When these agonists are administered at theime of meal ingestion, this results in impaired accom-odation and is associated with early satiety.88,91 Relax-

tion of the proximal stomach can be activated by duo-enal distention or nutrient infusion via a vagovagaleflex pathway,92,93 and it requires activation of intrinsicitrergic neurons in the stomach.94 Administration of aitric oxide synthase inhibitor induces impaired accom-odation in humans, and this is associated with early

atiety.95 These observations add further support to theypothesis that impaired accommodation is the mecha-ism underlying the symptom of early satiety.

Hypersensitivity to Gastric Distention

One study found an association between hyper-ensitivity to gastric distention, as determined by a gas-ric barostat study, and symptoms of pain and belching.9

owever, this apparent association could be influencedy a bias to report pain. In keeping with this possibility,significant association was found between symptoms ofain, hypersensitivity to gastric distention, and severalsychopathologic mechanisms, including neuroticism,omatization, a history of abuse, and health-related qual-ty of life dimensions. Attempts to induce hypersensitiv-ty in healthy subjects using a nitric oxide synthasenhibitor were not successful.95,96 Recent data showedhat the N-methyl-D-aspartate receptor antagonist dex-romethorphan sensitized the stomach to distention in

able 6. Summary of Reported Associations Between PathopDyspepsia

Mechanism

elayed gastric emptying Postprypersensitivity to gastric distention Epigas

mpaired accommodation Early s. pylori infection Epigasuodenal lipid hypersensitivity Nauseuodenal acid hypersensitivity Nausensuppressed phasic contractility Bloatintypical nonerosive reflux disease Epigas

he absence of an effect on gastric compliance.97 How-ver, this drug is not very selective, and it is unclearhether this constitutes a valid model of visceral hyper-

ensitivity and whether pretreatment with an N-methyl--aspartate antagonist induces dyspepsia-like symptomsfter ingestion of a meal.

Other Mechanisms

Acute H. pylori infection induces dyspepsia-likeymptoms, but these are transient.98 Nausea induced byestibular stimulation is also associated with abnormalitiesf gastric electrical rhythm, suggesting that this may be aecondary phenomenon accompanying nausea rather than arimary mechanism.99 These observations question the di-ect pathophysiologic relevance of H. pylori and gastriclectrical dysrhythmias.

In healthy subjects, duodenal acid infusion sensitizes theroximal stomach and the duodenum to distention and isble to induce dyspepsia-like symptoms.100,101 Administra-ion of the cholinesterase inhibitor neostigmine before aeal induces unsuppressed postprandial phasic contractions

n healthy subjects, and this is associated with increasedcores for several dyspeptic symptoms.102 These observa-ions suggest that increased duodenal acid exposure andnsuppressed postprandial phasic contractility of the prox-mal stomach are mechanisms potentially involved in theathogenesis of dyspeptic symptoms. Table 6 summarizeshe reported associations between symptom patterns andathophysiologic mechanisms in functional dyspepsia.

Pathogenesis

The pathogenesis of functional dyspepsia is ob-cure, but a postinfectious or inflammatory origin haseen suggested for irritable bowel syndrome.103 More-ver, gastroparesis has been reported after a viral infec-ion.104 Using a questionnaire in 400 consecutive pa-ients with functional dyspepsia, we found that 17% hadhistory with acute onset, suggestive of a postinfectiousrigin.10 These patients had a particularly high preva-

ologic Mechanisms and Symptom Pattern in Functional

sociated symptoms References

l fullness, nausea, vomiting 7, 11, 17, 36ain, belching, weight loss 9, 17, weight loss 8, 10, 35, 36ain 14, 28, 56

66, 67, 6871

sence of nausea 79ain 111

hysi

As

andiatric patietytric paag, abtric p

lsnwdrt

tedtasvpsudcpdpaae

awgmd

gnrcppaesisqdhp

achtsFpif

fttbin(mfntndewabpfsa

suaptetoppgwispatiu


ence of impaired accommodation. Because the proximaltomach in these patients relaxed to administration of aitric oxide donor but did not respond to sumatriptan,hich releases nitric oxide through activation of 5-hy-roxytryptamine (5-HT)1 receptors on nitrergic neu-ones, the abnormality is attributable to a dysfunction athe level of gastric nitrergic neurons.10

As previously mentioned, whether psychological fac-ors have a pathogenetic role in functional dyspepsia,specially in patients with hypersensitivity to gastricistention, or whether they are disease modulators de-ermining health care seeking, perception of symptoms,nd the outcome of the disorder is not known. There areeveral sources of evidence for a role of the central ner-ous system in visceral hypersensitivity. Studies in ex-erimental animals indicate that acute psychologicaltress facilitates increased sensitivity to visceral stim-li.105 In line with such a finding, rats genetically pre-isposed to anxiety have been shown to display an in-reased visceral sensitivity.106 Similarly, in humans, theerception of gut distention has been found to be re-uced during periods of distraction and increased duringeriods of attentiveness or during mental stress associ-ted with anxiety.107 However, the role of central factorsnd stress in visceral hypersensitivity and symptom gen-ration in functional dyspepsia remains to be established.

Finally, an association between dyspeptic symptomsnd a functional polymorphism in a G-protein subunitas reported.108 It remains to be established whether thisenotype is associated with any specific pathophysiologicechanism, the likelihood of postinfectious functional

isorders, or altered psychosocial features.

Clinical Presentation and Diagnosis

Patients with predominant heartburn or acid re-urgitation should, according to the Rome II criteria,ot be included in the dyspeptic spectrum but should beeferred to as having gastroesophageal reflux disease be-ause the management differs substantially.5 It has beenroposed that a substantial number of patients withredominant discomfort or pain centered in the upperbdomen actually have atypical reflux disease.109 How-ver, by using a simple questionnaire to screen for refluxymptoms,110 only a minority of patients with predom-nant dyspeptic symptoms have pathologic reflux ashown by 24-hour pH measurement.111 The use of theseuestionnaires in clinical practice may prove useful toetect patients who actually have reflux disease, with aigher likelihood of being responders to treatment withroton pump inhibitors (PPIs).

There is also a huge overlap between functional dyspepsiand irritable bowel syndrome.2 For instance, in a referralenter, 46% of patients with functional dyspepsia proved toave concomitant irritable bowel syndrome, and these pa-ients were more likely to be female, have gastric hypersen-itivity, and have more severe symptoms in general.112

urthermore, many subjects change from predominant dys-eptic symptoms to bowel-related symptoms, indicatingrritable bowel syndrome, or the opposite during a 1-yearollow-up period.2

When a patient presents with dyspeptic symptoms, care-ul clinical evaluation and history taking are essential fea-ures to make a correct diagnosis of dyspepsia and to dis-inguish it from gastroesophageal reflux disease and irritableowel syndrome. Routine biochemistry is usually includedn the diagnostic workup, but the clinical value of this hasot been formally validated. So-called alarm symptomsprominent weight loss, recurrent vomiting, bleeding, ane-ia, dysphagia, jaundice, palpable mass) should be looked

or with great care and, if present, require additional diag-ostic investigation. If there are no sinister symptoms andhe patient is young (younger than 45–50 years) and doesot take nonsteroidal anti-inflammatory drugs, upper en-oscopy is rarely needed in the first line. However, earlyndoscopy is of course the gold standard in the diagnosticorkup of dyspeptic patients with more severe symptoms

nd may be associated with greater patient satisfaction,113

ut it is not possible to perform this procedure in allatients because of financial, practical, and patient-relatedactors and other factors such as availability. Instead, othertrategies can be considered, namely initial empirical ther-py114–116 or a “test and treat” approach.54

The American Gastroenterological Association pre-ented a medical position statement regarding the eval-ation of dyspepsia in 1998 and recommended the “testnd treat” strategy,117 meaning initial testing for theresence of H. pylori infection and, if present, eradicationherapy. H. pylori–negative patients should be offeredmpirical antisecretory or prokinetic therapy. Based onhe existing studies on the effect of H. pylori eradicationn functional dyspepsia,55 it can be assumed that mostatients will still be symptomatic after treatment of H.ylori and should in that case be offered endoscopy. Theseuidelines were recently questioned by Spiegel et al.,ho by using a so-called decision analysis found empir-

cal PPI therapy to be more cost effective, either as a firsttep or following a “test and treat” approach, when theatient has not responded favorably to eradication ther-py.118 Moreover, these decision analyses cannot be ex-rapolated to every country because of major differencesn the prevalence of H. pylori infection, prevalence oflcers, accessibility of endoscopy, and cost of endoscopy.

AbhcbmGeace

wpdaunbr

wwcssssadeab

tssadpsqatsbsd

sfbdpc

avrmpmHstt

Fa


head-to-head comparison of these strategies is needed,ut in the meantime both strategies may be used andave support in the literature. Although often used inlinical practice, the empirical prokinetic therapy haseen less well studied. An in-depth analysis of clinicalanagement steps in dyspepsia was recently published inASTROENTEROLOGY.119 In general practice, the initial

mpirical therapy is probably still the most widely usedpproach. A clinical management algorithm based onurrently available management guidelines and clinicalxperience is summarized in Figure 3.

Other investigations that might be considered in theorkup are, for instance, upper abdominal ultrasonogra-hy or computed tomography, small bowel radiography,uodenal biopsy to exclude celiac disease, 24-hour esoph-geal pH monitoring, and manometric studies of thepper gastrointestinal tract. These investigations shouldot be performed in all patients but instead should beased on the clinical picture, severity of symptoms, andefractoriness of the patient.

igure 3. A clinical management algorithm based on currently avail-ble management guidelines and clinical experience.

Psychological symptoms are also common in patientsith functional dyspepsia as compared with patientsith organic causes of dyspepsia, such as duodenal ul-

er.83 This may be more related to being a patienteeking health care for dyspepsia than related to dyspep-ia per se. A review found several psychosocial factorsuch as life event stress, psychological morbidity, per-onality, abuse history, and abnormal illness behaviornd beliefs to be important factors in the process thatetermines who will seek medical attention.120 The pres-nce of psychosocial factors in these patients should beddressed carefully but should not be overemphasizedecause a causal role has not been established so far.

Treatment

General Measures

Reassurance and education is of primary impor-ance in patients with functional dyspepsia. It has beenhown in irritable bowel syndrome that a positive phy-ician-patient interaction can reduce health care seeking,nd these findings are probably also valid for functionalyspepsia.121 Lifestyle and dietary measures are usuallyrescribed, although they have not been systematicallytudied. It seems logical to have patients eat more fre-uent, smaller meals and desirable to avoid food thatggravates symptoms. Because the presence of lipids inhe duodenum enhances the mechanosensitivity of thetomach, avoiding meals with a high fat content mighte advisable.67,68 Coffee and spicy foods containing cap-aicin are usually discouraged, although there is no evi-ence to link these food components to symptoms.122,123

In some patients, pharmacologic therapy will be con-idered. The pharmacologic treatments available to dateor the management of functional dyspepsia have onlyeen shown to be of limited efficacy. It seems logical thatirecting therapeutic approaches toward the underlyingathophysiologic disturbances should increase the effica-y,124 but this has not been proven.

Acid-Suppressive Drugs

In patients with gastroesophageal reflux, a trial ofntisecretory therapy has both therapeutic and diagnosticalue. Several studies have evaluated the use of H2-eceptor antagonists in functional dyspepsia, and a recenteta-analysis showed superiority over placebo in im-

rovement of pain but not for overall symptom improve-ent.125 PPIs have proven to be more effective than2-receptor antagonists and antacid-alginate in relieving

ymptoms of uninvestigated dyspepsia (comparable tohe initial empirical PPI treatment previously men-ioned).114–116 Of course, these studies not only included

ppddwpidedws

dpoeuatisThg

ppwpihml

ttnrrTswp

ptont

lmrivtHwidoatiimtdpsaripwso

edcttloletn

sgsmstTp


atients with functional dyspepsia but also patients witheptic ulcer disease and with gastroesophageal refluxisease. Large and well-controlled studies in functionalyspepsia have shown that treatment with omeprazoleas approximately 10%–15% better than placebo inatients with functional dyspepsia.15 However, this pos-tive effect was restricted to patients with reflux-likeyspepsia, a subgroup that actually is no longer consid-red to belong to functional dyspepsia, and to a lesseregree in patients with ulcer-like dyspepsia. In patientsith dysmotility-like dyspepsia, no effect could be ob-

erved.15

In a recent study in consecutive patients with functionalyspepsia without dominant symptoms of heartburn,athologic esophageal acid exposure was present in a subsetf patients who were characterized by a higher prevalence ofpigastric pain.111 This finding suggests that patients withlcer-like dyspepsia who respond to acid-suppressive ther-py may actually have gastroesophageal reflux disease. Onhe other hand, recent studies have suggested a role forncreased duodenal acid exposure and duodenal acid hyper-ensitivity in the pathogenesis of functional dyspepsia.71,72

reatment with PPIs tended to decrease duodenal acidypersensitivity, but so far no symptomatic benefit in thisroup of patients has been shown.126

Prokinetic Agents

Prokinetic agents, including metoclopramide, dom-eridone, and cisapride, are widely used in functional dys-epsia. The rationale is to use prokinetic drugs in patientsith delayed gastric emptying, in which they should im-rove symptoms of postprandial fullness, nausea, and vom-ting. However, studies available so far fail to prove thisypothesis, and evidence that the symptomatic improve-ent is related to enhancement of gastric emptying is

acking.127–130

Metoclopramide and domperidone are dopamine recep-or agonists with a stimulatory effect on upper gastrointes-inal motility. Unlike metoclopramide, domperidone doesot cross the blood-brain barrier. Cisapride facilitates theelease of acetylcholine in the myenteric plexus via 5-HT4

eceptor agonism and accelerates gastric emptying.127–130

he availability of cisapride is restricted due to cardiacafety issues. Recently, tegaserod, a partial 5-HT4 agonist,as found to accelerate gastric emptying, indicating itsossibility as a prokinetic agent.131

Recent reviews suggest that prokinetics, especially dom-eridone and cisapride, are more effective than placebo, buthe trials were often of poor quality with significant heter-geneity between studies.127–130 However, the gastroproki-etic effects of these drugs are limited, and the finding ofhe strong gastrokinetic actions of erythromycin, a macro-

ide antibiotic that acts as a motilin receptor agonist, waset with great enthusiasm.132 Several short-term studies

eported beneficial effects of treatment with erythromycinn gastroparesis.132–134 Different macrolide prokinetics, de-oid of antibiotic properties, were developed and one ofhese, ABT-229, was studied in large clinical trials.135

owever, the outcomes of clinical trials with ABT-229ere unequivocally disappointing with regard to symptom

mprovement, both in dyspeptic patients with and withoutelayed emptying. It has been argued that the negativeutcomes of the studies with ABT-229 show that acceler-tion of gastric emptying is not the correct therapeuticarget in functional dyspepsia,135 but there are also strongndications of tachyphylaxis with macrolide prokinet-cs.136,137 Furthermore, it is well established that erythro-ycin and related compounds impair gastric accommoda-

ion to a meal,89–91 thereby enhancing sensitivity to gastricistention,48 which may have contributed to the overalloor symptomatic effect. Cisapride and tegaserod werehown to enhance gastric accommodation to a meal138,139

nd are therefore less likely to worsen or induce symptomselated to impaired accommodation. In addition, in prelim-nary studies, we showed a tendency for tegaserod to im-rove upper gastrointestinal symptoms in female patientsith functional dyspepsia with normal gastric emptying,

uggesting that it may affect pathophysiologic mechanismsther than delayed gastric emptying.140

Eradication of H. pylori

The 4 largest published randomized trials on theffect of H. pylori eradication on symptoms in functionalyspepsia show somewhat conflicting results. A single-enter trial suggested a small superiority of eradicationreatment versus PPI treatment alone,141 but 3 multicenterrials had negative findings.142–144 Taken together, these 4arge studies suggest that the potential symptomatic benefitf H. pylori treatment in functional dyspepsia is probably ofimited importance. Other arguments in favor of the use ofradication therapy are protection against peptic ulcer, pu-ative protection against gastric cancer, and the short-termature of the treatment.145

Antidepressants

There is some evidence that tricyclic antidepres-ants are effective in treating patients with functionalastrointestinal disorders, including functional dyspep-ia.146,147 Generally, lower doses are used than for treat-ent of depression. Mianserin, at a high dose, was also

hown to be superior to placebo in patients with func-ional gastrointestinal disorders, including dyspepsia.148

he mechanism behind the positive effect has been pro-osed to be due to an effect on gastric sensitivity, but

taipuaTlammhmhdotdd

dlslcbopPshteewiTbp5hAusstpate

sfsacadpwtrSds

atairtmbs

nTtaptsc

tdpdcssSibitapqr


his could not be confirmed in the study by Mertz etl.147 In clinical practice, it seems that the positive effects not clearly related to the presence or absence of de-ression. It is unclear whether selective serotonin re-ptake inhibitors (SSRIs) are also effective treatmentlternatives for functional gastrointestinal disorders.hese drugs increase the availability of synaptically re-

eased 5-HT not only in the central nervous system butlso at the level of the enteric nervous system. Pretreat-ent with the SSRI paroxetine strongly enhanced theeal-induced relaxation of the proximal stomach in

ealthy subjects.149 This observation suggests involve-ent of 5-HT in the gastric accommodation reflex in

umans as well as a potential beneficial effect of SSRIs inyspeptic patients with impaired accommodation. In anpen-label study in dyspeptic patients with abnormali-ies on electrogastrography, only patients with coexistingepression improved and gastric myoelectrical activityid not improve.150

Fundus-Relaxing Drugs

It seems logical that restoring gastric accommo-ation in patients with impaired accommodation isikely to improve symptoms of early satiety. Short-termtudies have shown some benefit of nitrates,151 but pro-onged use is generally associated with undesirable vas-ular side effects due to the lack of specificity. Sildenafillocks phosphodiesterase type 5, which degrades nitricxide–stimulated guanosine 3=,5=-cyclic monophos-hate, thereby relaxing smooth muscle in various organs.retreatment with sildenafil also relaxes the proximaltomach,152 and trials evaluating phosphodiesterase in-ibitors in functional dyspepsia seem warranted. Similaro the central nervous system, serotonin reuptake in thenteric nervous system is also inhibited by SSRIs.153 Thenhancement of gastric accommodation by pretreatmentith the SSRI paroxetine suggests involvement of 5-HT

n the control of the accommodation reflex in humans.149

he 5-HT receptor involved has not been identified, butoth 5-HT1 and 5-HT4 receptors can mediate enhancedostprandial gastric relaxation. Pretreatment with the-HT4 receptor agonists cisapride and tegaserod en-ances gastric accommodation in healthy subjects.138,139

dministration of sumatriptan, a 5-HT1 receptor agonistsed in the treatment of migraine, relaxes the proximaltomach in healthy subjects.154 In short-term studies,ubcutaneous administration of sumatriptan was showno restore meal-induced relaxation in patients with im-aired gastric accommodation and to increase themount of calories ingested at maximum satiety in pa-ients with early satiety.8 Due to its pharmacologic prop-rties, cost, and mode of administration, subcutaneous

umatriptan is not suitable for long-term treatment ofunctional dyspepsia. A nasal-spray formulation ofumatriptan had no significant effect on proximal stom-ch function.155 Buspirone is a nonselective 5-HT1 re-eptor agonist used in the treatment of panic attacks. Inplacebo-controlled study in patients with functional

yspepsia, we confirmed that buspirone was superior tolacebo in alleviating dyspeptic symptoms and that thisas associated with an enhancement of the accommoda-

ion to a meal.156 Clonidine, an �2 receptor agonist, alsoelaxes the stomach and reduces gastric sensation.157

hort-term administration of clonidine was found toecrease meal-induced symptoms in functional dyspep-ia.50

Other Drugs

Dose-finding studies with the 5-HT3 receptorntagonist alosetron showed potential benefit in func-ional dyspepsia.158 The mechanisms behind its effectre at present unclear. No effect on gastric sensitivityn healthy volunteers has been shown,159 but 5-HT3

eceptor antagonism reduces duodenal lipid sensitivi-y.63 Alosetron was on the U.S. market for approxi-ately 6 months for diarrhea-predominant irritable

owel syndrome, but its use is now restricted due toafety issues.160

Cholecystokinin receptor antagonists also reduce duode-al lipid sensitivity and are currently under evaluation.64,66

he � opioid agonist fedotozine decreases gastric sensitivityo distentions,161 and it showed superiority over placebo inplacebo-controlled study in patients with functional dys-epsia.162 However, development of this drug has not con-inued. Asimadoline, another � opioid agonist that washown to decrease satiation and meal-induced fullness,163 isurrently still under evaluation.

A recent study showed that long-term administra-ion of red pepper was more effective than placebo inecreasing the intensity of dyspeptic symptoms inatients with functional dyspepsia.123 Such a contra-ictory result might be explained by the finding thatapsaicin initially produces sensitization but repeatedtimulation of the capsaicin receptor on capsaicin-ensitive primary afferents leads to desensitization.164

tudies of the effect of capsaicin on gastric sensitivityn humans, which showed acute sensitization followedy decreased perception of epigastric symptoms,165 aren keeping with this mechanism of action. In a con-rolled trial in patients with functional dyspepsia,rtichoke leaf extract was significantly better thanlacebo in alleviating symptoms and in improvinguality of life.166 The basis for this improvementemains to be identified.

ctdm

tfietcesntdppbaweatdptswais

mehosmwiiptpsa

rp


Psychological Interventions

Psychological factors are considered importantontributors to symptom severity in patients with func-ional gastrointestinal disorders, including functionalyspepsia.8,167 This suggests that psychological treat-ent alternatives might be useful in these patients.A review of clinical trials of psychological interven-

ions for functional dyspepsia showed potential bene-ts in the treatment of functional dyspepsia.168 How-ver, several studies did not control for additionalime and attention the patients received in the psy-hological intervention arms, making it difficult toxclude a contribution of nonspecific factors. Anothertudy controlled for this factor compared psychody-amic-interpersonal psychotherapy with supportiveherapy in 95 consecutive patients with functionalyspepsia who had failed to respond to conventionalharmacologic treatments.169 At the end of treatment,atients receiving psychotherapy had a significantlyetter outcome than those receiving supportive ther-py. One year after treatment, the symptom scoresere similar in both groups, but a post hoc analysis

xcluding patients with severe heartburn also showedpositive effect of psychotherapy at 1 year. Hypno-

herapy was also shown to be useful in functionalyspepsia in a randomized study compared with sup-ortive or medical therapy.170 In a follow-up of 1 year,he effect was maintained. Hence, assessing psycho-ocial issues and intervening at this level in patientsith functional dyspepsia seems to be a reasonable

pproach. However, in clinical practice, this approachs usually reserved for those with severe and extensiveymptomatology or refractory disease.

Conclusions

Functional dyspepsia is one of the most com-on disorders seen in general practice and by gastro-

nterologists. Functional dyspepsia seems to be aeterogenous disorder in which different pathophysi-logic disturbances are associated with differentymptom profiles. The available options for the treat-ent of functional dyspepsia are of limited efficacy,hich probably reflects the incomplete understand-

ng of the nature of this disorder. Current knowledges in support of empirical treatment with acid-sup-ressive agents and prokinetics as well as identifica-ion and treatment of H. pylori infection. Refractoryatients may benefit from treatment with antidepres-ants or psychological interventions. More effectivepproaches are badly needed, and this will probably

equire ongoing efforts to elucidate underlying patho-hysiology.

References1. Talley NJ, Zinsmeister AR, Schleck CD, Melton LJ III. Dyspepsia

and dyspepsia subgroups: a population-based study. Gastroen-terology 1992;102:1259–1268.

2. Agreus L, Svardsudd K, Nyren O, Tibblin G. Irritable bowel syn-drome and dyspepsia in the general population: overlap and lackof stability over time. Gastroenterology 1995;109:671–680.

3. Penston JG, Pounder RE. A survey of dyspepsia in Great Britain.Aliment Pharmacol Ther 1996;10:83–89.

4. Klauser AG, Voderholzer WA, Knesewitsch PA, Schindlbeck NE,Muller-Lissner SA. What is behind dyspepsia? Dig Dis Sci 1993;38:147–154.

5. Talley NJ, Stanghellini V, Heading RC, Koch KL, Malagelada JR,Tytgat GNJ. Functional gastroduodenal disorders. Gut 1999;45(suppl II):37–42.

6. Agreus L. Natural history of dyspepsia. Gut 2002;50(suppl 4):iv2–9.

7. Stanghellini V, Tosetti C, Paternico A, Barbara G, Morselli-LabateAM, Monetti N, Marengo M, Corinaldesi R. Risk indicators ofdelayed gastric emptying of solids in patients with functionaldyspepsia. Gastroenterology 1996;110:1036–1042.

8. Tack J, Piessevaux H, Coulie B, Caenepeel P, Janssens J. Roleof impaired gastric accommodation to a meal in functional dys-pepsia. Gastroenterology 1998;115:1346–1352.

9. Tack J, Caenepeel P, Fischler B, Piessevaux H, Janssens J.Symptoms associated with hypersensitivity to gastric distentionin functional dyspepsia. Gastroenterology 2001;121:526–535.

10. Tack J, Demedts I, Dehondt G, Caenepeel P, Fischler B, Zan-decki M, Janssens J. Clinical and pathophysiological character-istics of acute-onset functional dyspepsia. Gastroenterology2002;122:1738–1747.

11. Sarnelli G, Caenepeel P, Geypens B, Janssens J, Tack J. Symp-toms associated with impaired gastric emptying of solids andliquids in functional dyspepsia. Am J Gastroenterol 2003;98:783–788.

12. Tougas G, Chen Y, Hwang P, Liu MM, Eggleston A. Prevalenceand impact of upper gastrointestinal symptoms in the Canadianpopulation: findings from the DIGEST study. Am J Gastroenterol1999;94:2845–2854.

13. Jones MP, Talley NJ, Coulie B, Dubois D, Tack J. Clustering ofweight loss with symptoms of functional dyspepsia: a popula-tion-based study (abstr). Gastroenterology 2003;124:A390.

14. Stanghellini V, Tosetti C, Paternico A, De Giorgio R, Barbara G,Salvioli B, Corinaldesi R. Predominant symptoms identify differ-ent subgroups in functional dyspepsia. Am J Gastroenterol1999;94:2080–2085.

15. Talley NJ, Meineche-Schmidt V, Pare P, Duckworth M, RaisanenP, Pap A, Kordecki H, Schmid V. Efficacy of omeprazole infunctional dyspepsia: double-blind, randomized, placebo-con-trolled trials (the Bond and Opera studies). Aliment PharmacolTher 1998;12:1055–1065.

16. Talley NJ, Weaver AL, Tesmer DL, Zinsmeister AR. Lack ofdiscriminant value of dyspepsia subgroups in patients referredfor upper endoscopy. Gastroenterology 1993;105:1378–1386.

17. Fischler B, Vandenberghe J, Persoons P, De Gucht V, Broekaert D,Luyckx K, Tack J. Evidence-based subtypes in functional dyspepsiawith confirmatory factor analysis: psychosocial and physiopatho-logical correlates. Gastroenterology 2001;120:268–276.

18. Bisschops R, Geypens B, Ghoos I, Tack J. Timing of symptoms inrelation to the meal in pain-predominant versus discomfort-pre-dominant dyspepsia (abstr). Gastroenterology 2000;118:2544.

19. Arts J, Caenepeel P, Demedts I, Verbeke K, Tack J. Influence oferythromycin on gastric emptying and meal-related symptoms in

https://www.researchgate.net/publication/14336248_A_survey_of_dyspepsia_in_Great_Britain?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=

https://www.researchgate.net/publication/14336248_A_survey_of_dyspepsia_in_Great_Britain?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=

https://www.researchgate.net/publication/12842975_Functional_Gastroduodenal_Disorders?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/null?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=


https://www.researchgate.net/publication/14587548_Risk_factors_of_delayed_gastric_emptying_of_solids_in_patients_with_functional_dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/13453104_Role_of_impaired_gastric_accommodation_to_a_meal_in_functional_dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=














https://www.researchgate.net/publication/12853354_Predominant_symptoms_identify_different_subgroups_in_functional_dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/13443131_Efficacy_of_omeprazole_in_functional_dyspepsia_Double-blind_randomized_placebo-controlled_trials_the_Bond_and_Opera_studies?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=





https://www.researchgate.net/publication/14973930_Lack_of_discriminant_value_of_dyspepsia_subgroups_in_patients_referred_for_upper?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/246676011_Evidence-based_subtypes_in_functional_dyspepsia_with_confirmatory_factor_analysis_Psychosocial_and_physiopathological_correlates?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/246635955_Timing_of_symptoms_in_relation_to_the_meal_in_pain-predominant_versus_dLscomfort-predominant_dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=







https://www.researchgate.net/publication/12779360_Prevalence_and_impact_of_upper_gastrointestinal_symptoms_in_the_Canadian_population_Findings_from_The_DIGEST_study?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=





functional dyspepsia with delayed gastric emptying. Gut (inpress)

20. Wegener M, Borsch G, Schaffstein J, Reuter C, Leverkus F. Fre-quency of idiopathic gastric stasis and intestinal transit disordersin essential dyspepsia. J Clin Gastroenterol 1989;11:163–168.

21. Jian R, Ducrot F, Ruskone A, Chaussade S, Rambaud JC,Modigliani R, Rain JD, Bernier JJ. Symptomatic, radionuclideand therapeutic assessment of chronic idiopathic dyspepsia. Adouble-blind placebo-controlled evaluation of cisapride. Dig DisSci 1989;34:657–664.

22. Talley NJ, Shuter B, McCrudden G, Jones M, Hoschl R, Piper DW.Lack of association between gastric emptying of solids andsymptoms in nonulcer dyspepsia. J Clin Gastroenterol 1989;11:625–630.

23. Waldron B, Cullen PT, Kumar R, Smith D, Jankowskik J, Hop-wood D, Sutton D, Kennedy N, Campbell FC. Evidence for hypo-motility in non-ulcer dyspepsia: a prospective multifactorialstudy. Gut 1991;32:246–251.

24. Klauser AG, Voderholzer WA, Knesewitsch PA, Schindlbeck NE,Muller-Lissner SA. What is behind dyspepsia? Dig Dis Sci 1993;38:47–54.

25. Scott AM, Kellow JE, Shuter B, Cowan H, Corbett AM, Riley JW,Lunzer MR, Eckstein RP, Hoschl R, Lam SK, et al. Intragastricdistribution and gastric emptying of solids and liquids in func-tional dyspepsia. Lack of influence of symptom subgroups andH. pylori-associated gastritis. Dig Dis Sci 1993;38:2247–2254.

26. Quartero AO, de Wit NJ, Lodder AC, Numans ME, Smout AJ,Hoes AW. Disturbed solid-phase gastric emptying in functionaldyspepsia: a meta-analysis. Dig Dis Sci 1998;43:2028–2033.

27. Maes BD, Ghoos YF, Hiele MI, Rutgeerts PJ. Gastric emptyingrate of solids in patients with nonulcer dyspepsia. Dig Dis Sci1997;42:1158–1162.

28. Perri F, Clemente R, Festa V, Annese V, Quitadamo M, RutgeertsP, Andriulli A. Patterns of symptoms in functional dyspepsia:role of Helicobacter pylori infection and delayed gastric empty-ing. Am J Gastroenterol 1998;93:2082–2088.

29. Talley NJ, Verlinden M, Jones M. Can symptoms discriminateamong those with delayed or normal gastric emptying in dysmo-tility-like dyspepsia? Am J Gastroenterol 2001;96:1422–1428.

30. Ricci R, Bontempo I, La Bella A, De Tschudy A, Corazziari E.Dyspeptic symptoms and gastric antrum distribution. An ultra-sonographic study. Ital J Gastroenterol 1987;19:215–217.

31. Hausken T, Berstad A. Wide gastric antrum in patients withnon-ulcer dyspepsia. Effect of cisapride. Scand J Gastroenterol1992;27:427–432.

32. Troncon LEA, Bennett RJM, Ahluwalia NK, Thompson DG. Abnor-mal distribution of food during gastric emptying in functionaldyspepsia patients. Gut 1994;35:327–332.

33. Gilja OH, Hausken T, Wilhelmsen I, Berstad A. Impaired accom-modation of proximal stomach to a meal in functional dyspep-sia. Dig Dis Sci 1996;41:689–696.

34. Salet GAM, Samsom M, Roelofs JMM, van Berge HenegouwenGP, Smout AJPM, Akkermans LMA. Responses to gastric dis-tention in functional dyspepsia. Gut 1998;42:823–829.

35. Kim DY, Delgado-Aros S, Camilleri M, Samsom M, Murray JA,O’Connor MK, Brinkmann BH, Stephens DA, Lighvani SS, BurtonDD. Noninvasive measurement of gastric accommodation inpatients with idiopathic nonulcer dyspepsia. Am J Gastroenterol2001;96:3099–3105.

36. Boeckxstaens GE, Hirsch DP, Kuiken SD, Heisterkamp SH,Tytgat GN. The proximal stomach and postprandial symptoms infunctional dyspeptics. Am J Gastroenterol 2002;97:40–48.

37. Piessevaux H, Tack J, Walrand S, Pauwels S, Geubel A. Intra-gastric distribution of a standardized meal in health and func-tional dyspepsia: correlation with specific symptoms. Neurogas-troenterol Motil 2003;15:447–455.

38. Ladabaum U, Koshy SS, Woods ML, Hooper FG, Owyang C,Hasler WL. Differential symptomatic and electrogastrographiceffects of distal and proximal human gastric distension. Am JPhysiol 1998;275:G418–G424.

39. Marzio L, Falcucci M, Grossi L, Ciccaglione FA, Malatesta MG,Castellano A, Ballone E. Proximal and distal gastric distensionin normal subjects and H. pylori-positive and -negative dyspepticpatients and correlation with symptoms. Dig Dis Sci 1998;43:2757–2763.

40. Caldarella MP, Azpiroz F, Malagelada JR. Antro-fundic dysfunctionsin functional dyspepsia. Gastroenterology 2003;124:1220–1229.

41. Lee KJ, Vos R, Janssens J, Tack J. Differences in the sensori-motor response to distension between the proximal and distalstomach in humans. Gut 2004;53:938–943.

42. Camilleri M, Coulie B, Tack J. Visceral hypersensitivity: facts,speculations and challenges. Gut 2001;48:125–131.

43. Lemann M, Dederding JP, Flourie B, Franchisseur C, RambaudJC, Jian R. Abnormal perception of visceral pain in response togastric distension in chronic idiopathic dyspepsia. The irritablestomach syndrome. Dig Dis Sci 1991;36:1249–1254.

44. Bradette M, Pare P, Douville P, Morin A. Visceral perception inhealth and functional dyspepsia. Crossover study of gastricdistensions with placebo and domperidone. Dig Dis Sci 1991;36:52–58.

45. Mearin F, Cucala M, Azpiroz F, Malagelada JR. The origin ofsymptoms on the brain-gut axis in functional dyspepsia. Gastro-enterology 1991;101:999–1006.

46. Mertz H, Fullerton S, Naliboff B, Mayer EA. Symptoms andvisceral perception in severe functional and organic dyspepsia.Gut 1998;42:814–822.

47. Rhee PL, Kim YH, Son HJ, Kim JJ, Koh KC, Paik SW, Rhee JC,Choi KW. Evaluation of individual symptoms cannot predictpresence of gastric hypersensitivity in functional dyspepsia. DigDis Sci 2000;45:1680–1684.

48. Piessevaux H, Tack J, Wilmer A, Coulie B, Geubel A, Janssens J.Perception of changes in wall tension of the proximal stomach inhumans. Gut 2001;49:203–208.

49. Distrutti E, Azpiroz F, Soldevilla A, Malagelada JR. Gastric walltension determines perception of gastric distension. Gastroen-terology 1999;116:1035–1042.

50. Tack J, Caenepeel P, Corsetti M, Janssens J. Role of tensionreceptors in dyspeptic patients with hypersensitivity to gastricdistention. Gastroenterology 2004;127:1058–1066.

51. Cervero F. Sensory innervation of the viscera: peripheral basisof visceral pain. Physiol Rev 1994;74:95–138.

52. Vandenberghe J, Vos R, Janssens J, Tack J. Visceral hyperalge-sia in functional dyspepsia (FD): Pain-specific or multimodalafferent pathways? Gastroenterology 2002;122(Suppl. 1):A34.

53. Tack J, Bisschops R, Caenepeel P, Vos R, Janssens J. Patho-physiological relevance of fasting versus postprandial sensitiv-ity testing in functional dyspepsia (abstr). Gastroenterology2002;122:A301.

54. Malfertheiner P, Megraud F, O’Morain C, Hungin AP, Jones R,Axon A, Graham DY, Tytgat G. Current concepts in the manage-ment of Helicobacter pylori infection—the Maastricht 2-2000Consensus Report. Aliment Pharmacol Ther 2002;16:167–180.

55. Danesh J, Lawrence M, Murphy M, Roberts S, Collins R. Sys-tematic review of the epidemiological evidence on Helicobacterpylori infection and nonulcer or uninvestigated dyspepsia. ArchIntern Med 2000;160:1192–1198.

56. Tucci A, Corinaldesi R, Stanghellini V, Tosetti C, Di Febo G, PaparoGF, Varoli O, Paganelli GM, Labate AM, Masci C, et al. Helicobacterpylori infection and gastric function in patients with chronic idio-pathic dyspepsia. Gastroenterology 1992;103:768–774.

57. Mearin F, de Ribot X, Balboa A, Salas A, Varas MJ, Cucala M,Bartolome R, Armengol JR, Malagelada JR. Does Helicobacter

https://www.researchgate.net/publication/226618547_What_is_behind_dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/20418595_Frequency_of_Idiopathic_Gastric_Stasis_and_Intestinal_Transit_Disorders_in_Essential_Dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/20501963_Jian_R_Ducrot_F_Ruskone_A_et_al_Symptomatic_radionuclide_and_therapeutic_assessment_of_chronic_idiopathic_dyspepsia_A_double-blind_placebo-controlled_evaluation_of_cisapride?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=





https://www.researchgate.net/publication/20570877_Lack_of_Association_Between_Gastric_Emptying_of_Solids_and_Symptoms_in_Nonulcer_Dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/21143429_Evidence_for_hypomotility_in_non-ulcer_dyspepsia_A_prospective_multifactorial_study?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/14937122_Intragastric_distribution_and_gastric_emptying_of_solids_and_liquids_in_functional_dyspepsia_Lack_of_influence_of_symptom_subgroups_and_H_pylori-associated_gastritis?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=





https://www.researchgate.net/publication/13533255_Disturbed_solid-phase_gastric_emptying_in_functional_dyspepsia_a_meta-analysis?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/14018427_Gastric_Emptying_Rate_of_Solids_in_Patients_with_Nonulcer_Dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/13467070_Patterns_of_symptoms_in_functional_dyspepsia_Role_of_Helicobacter_pylori_infection_and_delayed_gastric_emptying?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=







https://www.researchgate.net/publication/291999896_Dyspeptic_symptoms_and_gastric_antrum_distribution_An_ultrasonographic_study?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/21627004_Wide_Gastric_Antrum_in_Patients_with_Non-Ulcer_Dyspepsia_Effect_of_Cisapride?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/15049597_Abnormal_distribution_of_food_during_gastric_emptying_in_functional_dyspepsia_patients?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/14528132_Impaired_accomodation_of_proximal_stomach_to_a_meal_in_functional_dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=











https://www.researchgate.net/publication/13406524_Proximal_and_Distal_Gastric_Distension_in_Normal_Subjects_and_H_pylori-Positive_and_-Negative_Dyspeptic_Patients_and_Correlation_with_Symptoms?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=












https://www.researchgate.net/publication/21261797_Abnormal_perception_of_visceral_pain_in_response_to_gastric_distension_in_chronic_idiopathic_dyspepsia_The_irritable_stomach_syndrome?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/21265711_The_origin_of_symptoms_on_the_brain-gut_axis_in_functional_dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/13593168_Symptoms_and_visceral_perception_in_severe_functional_and_organic_dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/226049758_Evaluation_of_Individual_Symptoms_Cannot_Predict_Presence_of_Gastric_Hypersensitivity_in_Functional_Dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=







https://www.researchgate.net/publication/13076932_Gastric_wall_tension_determine_perception_of_gastric_distension?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=






https://www.researchgate.net/publication/14903235_Cervero_P_Sensory_Innervation_of_the_Viscera_Peripheral_Basis_of_Visceral_Pain?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=

https://www.researchgate.net/publication/14903235_Cervero_P_Sensory_Innervation_of_the_Viscera_Peripheral_Basis_of_Visceral_Pain?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=

https://www.researchgate.net/publication/296254914_Visceral_hyperalgesia_in_functional_dyspepsia_FD_Pain-specific_or_multimodal_afferent_pathways?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/296254606_Pathophysiological_relevance_of_fasting_versus_postprandial_sensitivity_testing_in_functional_dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=








https://www.researchgate.net/publication/21655647_Helicobacter_pylori_infection_and_gastric_function_in_patients_with_chronic_idiopathic_dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/13593169_Response_to_gastric_distension_in_functional_dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/13561825_Differential_symptomatic_and_electrogastrographic_effects_of_distal_and_proximal_human_gastric_distension?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/254194244_Current_Concepts_in_the_Management_of_Helicobacter_pylori_Infection_-_The_Maastricht_2-2000_Consensus_Report_Updated_Contents?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=





pylori infection increase gastric sensitivity in functionaldyspepsia? Gut 1995;37:47–51.

58. Saslow SB, Thumshirn M, Camilleri M, Locke GR III, ThomfordeGM, Burton DD, Hanson RB. Influence of H. pylori infection ongastric motor and sensory function in asymptomatic volunteers.Dig Dis Sci 1998;43:258–264.

59. Thumshirn M, Camilleri M, Saslow SB, Williams DE, Burton DD,Hanson RB. Gastric accommodation in non-ulcer dyspepsia andthe roles of Helicobacter pylori infection and vagal function. Gut1999;44:55–64.

60. Rhee PL, Kim YH, Son HJ, Kim JJ, Koh KC, Paik SW, Rhee JC,Choi KW. Lack of association of Helicobacter pylori infectionwith gastric hypersensitivity or delayed gastric emptying in func-tional dyspepsia. Am J Gastroenterol 1999;94:3165–3169.

61. Sarnelli G, Janssens J, Tack J. Helicobacter pylori is not asso-ciated with symptoms and pathophysiological mechanisms offunctional dyspepsia. Dig Dis Sci 2003;48:2229–2236.

62. Houghton LA, Mangnall YF, Dwivedi A, Read N. Increased nutri-ent sensitivity in a subgroup of patients with nonulcer dyspepsia(NUD). Gut 1990;31:A1185.

63. Feinle C, Read NW. Ondansetron reduces nausea induced bygastroduodenal stimulation without changing gastric motility.Am J Physiol 1996;271:G591–G597.

64. Feinle C, D’Amato M, Read NW. Cholecystokinin-A receptors mod-ulate gastric sensory and motor responses to gastric distensionand duodenal lipid. Gastroenterology 1996;110:1379–1385.

65. Feinle C, Rades T, Otto B, Fried M. Fat digestion modulatesgastrointestinal sensations induced by gastric distention and du-odenal lipid in humans. Gastroenterology 2001;120:1100–1107.

66. Feinle C, Meier O, Otto B, D’Amato M, Fried M. Role of duodenallipid and cholecystokinin A receptors in the pathophysiology offunctional dyspepsia. Gut 2001;48:347–355.

67. Barbera R, Feinle C, Read NW. Nutrient-specific modulation ofgastric mechanosensitivity in patients with functional dyspep-sia. Dig Dis Sci 1995;40:1636–1641.

68. Barbera R, Feinle C, Read NW. Abnormal sensitivity to duodenallipid infusion in patients with functional dyspepsia. Eur J Gas-troenterol Hepatol 1995;7:1051–1057.

69. Zerbib F, Bruley Des Varannes S, Scarpignato C, Leray V,D’Amato M, Roze C, Galmiche JP. Endogenous cholecystokininin postprandial lower esophageal sphincter function and fundictone in humans. Am J Physiol 1998;275:G1266–G1273.

70. DeMarchi B, Vos R, Deprez P, Janssens J, Tack J. Influence of alipase inhibitor on gastric sensitivity and accommodation to anorally ingested meal. Aliment Pharmacol Ther 2004;19:1261–1268.

71. Samsom M, Verhagen MA, van Berge Henegouwen GP, SmoutAJPM. Abnormal clearance of exogenous acid and increasedacid sensitivity of the proximal duodenum in dyspeptic patients.Gastroenterology 1999;116:515–520.

72. Lee K, Demarchi B, Demedts I, Sifrim D, Raeymaekers P, TackJ. A pilot study on duodenal acid exposure and its relationship tosymptoms in functional dyspepsia with prominent nausea. Am JGastroenterol 2004;99:1765–1773.

73. Camilleri M, Brown ML, Malagelada JR. Relationship betweenimpaired gastric emptying and abnormal gastrointestinal motil-ity. Gastroenterology 1986;91:94–99.

74. Jebbink HJ, van Berge Henegouwen GP, Akkermans LM, SmoutAJ. Small intestinal motor abnormalities in patients with func-tional dyspepsia demonstrated by ambulatory manometry. Gut1996;38:694–700.

75. Wilmer A, Van Cutsem E, Andrioli A, Tack J, Coremans G,Janssens J. Ambulatory gastrojejunal manometry in severe mo-tility-like dyspepsia: lack of correlation between dysmotility,symptoms, and gastric emptying. Gut 1998;42:235–242.

76. Lin W, Eaker EY, Sarosiek I, McCallum RW. Gastric myoelectricalactivity and gastric emptying in patients with functional dyspep-sia. Am J Gastroenterol 1999;94:2384–2389.

77. Parkman HP, Miller MA, Trate D, Knight LC, Urbain JL, MaurerAH, Fisher RS. Electrogastrography and gastric emptying scin-tigraphy are complementary for assessment of dyspepsia. J ClinGastroenterol 1997;24:214–219.

78. Azpiroz F, Malagelada JR. Gastric tone measured by an elec-tronic barostat in health and postsurgical gastroparesis. Gas-troenterology 1987;92:934–943.

79. Simren M, Vos R, Janssens J, Tack J. Unsuppressed postpran-dial phasic contractility in the proximal stomach in functionaldyspepsia: relevance to symptoms. Am J Gastroenterol 2003;98:2169–2175.

80. Hausken T, Svebak S, Wilhelmsen I, Haug TT, Olafsen K, Pet-tersson E, Hveem K, Berstad A. Low vagal tone and antraldysmotility in patients with functional dyspepsia. PsychosomMed 1993;55:12–22.

81. Holtmann G, Goebell H, Jockenhoevel F, Talley NJ. Altered vagaland intestinal mechanosensory function in chronic unexplaineddyspepsia. Gut 1998;42:501–506.

82. Troncon LE, Thompson DG, Ahluwalia NK, Barlow J, Heggie L.Relations between upper abdominal symptoms and gastric dis-tension abnormalities in dysmotility like functional dyspepsiaand after vagotomy. Gut 1995;37:17–22.

83. Wilhelmsen I, Haug TT, Ursin H, Berstad A. Discriminant analy-sis of factors distinguishing patients with functional dyspepsiafrom patients with duodenal ulcer. Significance of somatization.Dig Dis Sci 1995;40:1105–1111.

84. Bennett EJ, Kellow JE, Cowan H, Scott AM, Shuter B, Langelud-decke PM, Hoschl R, Jones MP, Tennant CC. Suppression ofanger and gastric emptying in patients with functional dyspep-sia. Scand J Gastroenterol 1992;27:869–874.

85. Haug TT, Svebak S, Hausken T, Wilhelmsen I, Berstad A, UrsinH. Low vagal activity as mediating mechanism for the relation-ship between personality factors and gastric symptoms in func-tional dyspepsia. Psychosom Med 1994;56:181–186.

86. Tougas G, Chen Y, Luo D, Salter J, D’Elia T, Earnest DL. Tegaserodimproves gastric emptying in patients with gastroparesis and dys-peptic symptoms (abstr). Gastroenterology 2003;124:A54.

87. Coulie B, Tack J, Maes B, et al. Sumatriptan delays gastricemptying of a solid/meal without induction of epigastric symp-toms (abstr). Gastroenterology 1996;110:A651.

88. Tack J, Caenepeel P, Piessevaux H, Cuomo R, Janssens J.Assessment of meal-induced gastric accommodation by a sati-ety drinking test in health and in severe functional dyspepsia.Gut 2003;52:1271–1277.

89. Bruley des Varannes S, Parys V, Ropert A, Chayvialle JA, Roze C,Galmiche JP. Erythromycin enhances fasting and postprandial prox-imal gastric tone in humans. Gastroenterology 1995;109:32–39.

90. Kamerling I, Van Haarst A, Burggraaf J, Schoemaker RC,Biemond I, Heinwerling H, Jones R, Cohen AF, Masclee AA.Motilin effects on the proximal stomach in patients with func-tional dyspepsia and healthy volunteers. Am J Physiol 2003;284:G776–G781.

91. Coulie B, Vandaele P, Tack J, Peeters T, Janssens J. Motilinincreases gastric fundus tone in man via activation of a cholin-ergic pathway. Gastroenterology 1997;112(Suppl.):A1140.

92. Azpiroz F, Malagelada JR. Vagally mediated gastric relaxationinduced by intestinal nutrients in the dog. Am J Physiol 1986;251:G727–G735.

93. De Ponti F, Azpiroz F, Malagelada JR. Reflex gastric relaxation inresponse to distention of the duodenum. Am J Physiol 1987;252:G595–G601.

94. Desai KM, Sessa WC, Vane JR. Involvement of nitric oxide in thereflex relaxation of the stomach to accommodate food or fluid.Nature 1991;35:477–479.

https://www.researchgate.net/publication/51308740_Influence_of_H_pylori_Infection_on_Gastric_Motor_and_Sensory_Function_in_Asymptomatic_Volunteers?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/14308889_Ondansetron_reduces_nausea_induced_by_gastroduodenal_stimulation_without_changing_gastric_motility?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=

https://www.researchgate.net/publication/14308889_Ondansetron_reduces_nausea_induced_by_gastroduodenal_stimulation_without_changing_gastric_motility?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=

https://www.researchgate.net/publication/14587598_CCK-A_receptors_modulate_gastric_sensory_and_motor_responses_to_gastric_distension_and_duodenal_lipid?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=









https://www.researchgate.net/publication/15550118_Nutrient-specific_modulation_of_gastric_mechanosensitivity_in_patients_with_functional_dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/14520665_Abnormal_sensitivity_to_duodenal_lipid_infusion_in_patients_with_functional_dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/13443497_Endogenous_cholecystokinin_in_postprandial_esophageal_sphincter_function_and_fundic_tone_in_humans?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=












https://www.researchgate.net/publication/19452022_Relation_between_emphasized_gastric_emptying_and_abnormal_gastrointestinal_motility?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/14495464_Small_intestinal_motor_abnormalities_in_patients_with_functional_dyspepsia_demonstrated_by_ambulatory_manometry?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/13966993_Electrogastrography_and_Gastric_Emptying_Scintigraphy_Are_Complementary_for_Assessment_of_Dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/19604924_Gastric_tone_measured_by_an_electronic_barostat_in_health_and_surgical_gastroparesis?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=







https://www.researchgate.net/publication/14752048_Low_vagal_tone_and_antral_dysmotility_in_patients_with_functional_dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/13668673_Altered_vagal_and_intestinal_mechanosensory_function_in_chronic_unexplained_dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/15525831_Relations_between_upper_abdominal_symptoms_and_gastric_distension_abnormalities_in_dysmotility_like_functional_dyspepsia_and_after_vagotomy?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/15470460_Discriminant_analysis_of_factors_distinguishing_patients_with_functional_dyspepsia_from_patients_with_duodenal_ulcer_Significance_of_somatization?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/21715258_Suppression_of_Anger_and_Gastric_Emptying_in_Patients_with_Functional_Dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/15114211_Low_vagal_activity_as_mediating_mechanism_for_the_relationship_between_personality_factors_and_gastric_symptoms_in_functional_dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=








https://www.researchgate.net/publication/15402240_Bruley_Des_Varannes_S_Parys_V_Ropert_A_et_al_Erythromycin_enhances_fasting_and_postprandial_proximal_gastric_tone_in_humans?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/19373076_Vagally_mediated_gastric_relaxation_induced_by_intestinal_nutrients_in_the_dog?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/20272155_Reflex_gastric_relaxation_in_response_to_distension_of_the_duodenum?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/51329259_Ambulatory_gastrojejunal_manometry_in_severe_motility-like_dyspepsia_Lack_of_correlation_between_dysmotility_symptoms_and_gastric_emptying?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/12816147_Gastric_myoelectrical_activity_and_gastric_emptying_in_patients_with_functional_dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/21481194_Involvement_of_nitric_oxide_in_the_reflex_relaxation_of_the_stomach_to_accommodate_food_or_fluid_Nature_351_477-479?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=





https://www.researchgate.net/publication/46595203_Abnormal_clearance_of_exogenous_acid_and_increased_acid_sensitivity_of_the_proximal_duodenum_in_dyspeptic_patients?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=









https://www.researchgate.net/publication/292318520_Lack_of_association_of_Helicobacter_pylori_infection_with_gastric_hypersensitivity_or_delayed_gastric_emptying_in_functional_dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1


95. Tack J, Demedts I, Meulemans A, Schuurkes J, Janssens J. Roleof nitric oxide in the gastric accommodation reflex and in mealinduced satiety in humans. Gut 2002;51:219–224.

96. Kuiken SD, Vergeer M, Heisterkamp SH, Tytgat GN, Boeckxs-taens GE. Role of nitric oxide in gastric motor and sensoryfunctions in healthy subjects. Gut 2002;51:212–218.

97. Kuiken SD, Lei A, Tytgat GN, Holman R, Boeckxstaens GE. Effectof the low-affinity, non-competitive N-methyl-d-aspartate receptorantagonist dextromethorphan on visceral perception in healthyvolunteers. Aliment Pharmacol Ther 2002;16:1955–1962.

98. Sobala GM, Crabtree JE, Dixon MF, Schorah CJ, Taylor JD,Rathbone BJ, Heatley RV, Axon AT. Acute Helicobacter pyloriinfection: clinical features, local and systemic immune re-sponse, gastric mucosal histology and gastric juice ascorbicacid concentrations. Gut 1991;32:1415–1418.

99. Kim MS, Chey WD, Owyang C, Hasler WL. Role of plasma vaso-pressin as a mediator of nausea and gastric slow wave dysrhyth-mias in motion sickness. Am J Physiol 1997;272:G853–G862.

00. Lee KJ, Vos R, Janssens J, Tack J. Influence of duodenalacidification on the sensorimotor function of the proximal stom-ach in humans. Am J Physiol 2004;286:G278–G284.

01. Di Stefano M, Vos R, Janssens J, Tack J. Effect of acid perfusionof the duodenum on induction of dyspeptic symptoms in healthyvolunteers (abstr). Gastroenterology 2003;124:A80.

02. Di Stefano M, Vos R, Janssens J, Tack J. Neostigmine-inducedincrease of proximal stomach contraction and dyspeptic symp-toms in healthy volunteers (abstr). Gastroenterology 2003;124:A225.

03. Gwee KA, Graham JC, McKendrick MW, Collins SM, Marshall JS,Read NW. Psychometric scores and persistence of irritablebowel after infectious diarrhea. Lancet 1996;347:150–153.

04. Bityutskiy LP, Soykan I, McCallum RW. Viral gastroparesis: asubgroup of idiopathic gastroparesis. Clinical characteristicsand long-term outcomes. Am J Gastroenterol 1997;92:1501–1504.

05. Gue M, Del Rio-Lacheze C, Eutamene H, Theodorou V, Fio-ramonti J, Bueno L. Stress-induced visceral hypersensitivity torectal distension in rats: role of CRF and mast cells. Neurogas-troenterol Motil 1997;9:271–279.

06. Gunter WD, Shepard JD, Foreman RD, Myers DA, Greenwood-Van Meerveld B. Evidence for visceral hypersensitivity in high-anxiety rats. Physiol Behav 2000;69:379–382.

07. Accarino AM, Azpiroz F, Malagelada JR. Attention and distrac-tion: effects on gut perception. Gastroenterology 1997;113:415–422.

08. Holtmann G, Siffert W, Haag S, Mueller N, Langkafel M, Senf W,Zotz R, Talley NJ. G-protein beta 3 subunit 825 CC genotype isassociated with unexplained (functional) dyspepsia. Gastroen-terology 2004;126:971–979.

09. Bytzer P, Talley NJ. Dyspepsia. Ann Intern Med 2001;134:815–822.

10. Johnsson F, Roth Y, Damgaard Pedersen NE, Joelsson B. Cime-tidine improves GERD symptoms in patients selected by avalidated GERD questionnaire. Aliment Pharmacol Ther 1993;7:81–86.

11. Tack J, Lee K, Sifrim D, Janssens J. Prevalence and symptom-atic impact of non-erosive reflux disease in functional dyspep-sia. Gastroenterology 2002;122(Suppl. 1):786.

12. Corsetti M, Caenepeel P, Fischler B, Janssens J, Tack J. Impactof coexisting irritable bowel syndrome on symptoms and patho-physiological mechanisms in functional dyspepsia. Am J Gas-troenterol 2004;99:1152–1159.

13. Bytzer P, Hansen JM, Schaffalitzky de Muckadell OB. EmpiricalH2-blocker therapy or prompt endoscopy in management ofdyspepsia. Lancet 1994;343:811–816.

14. Goves J, Oldring JK, Kerr D, Dallara RG, Roffe EJ, Powell JA,Taylor MD. First line treatment with omeprazole provides an

effective and superior alternative strategy in the managementof dyspepsia compared to antacid/alginate liquid: a multicentrestudy in general practice. Aliment Pharmacol Ther 1998;12:147–157.

15. Jones RH, Baxter G. Lansoprazole 30 mg daily versus ranitidine150 mg b.d. in the treatment of acid-related dyspepsia in gen-eral practice. Aliment Pharmacol Ther 1997;11:541–546.

16. Mason I, Millar LJ, Sheikh RR, Evans WM, Todd PL, Turbitt ML,Taylor MD. The management of acid-related dyspepsia in gen-eral practice: a comparison of an omeprazole versus an antacid-alginate/ranitidine management strategy. Compete ResearchGroup. Aliment Pharmacol Ther 1998;12:263–271.

17. American Gastroenterological Association medical positionstatement: evaluation of dyspepsia. Gastroenterology 1998;114:579–581.

18. Spiegel BM, Vakil NB, Ofman JJ. Dyspepsia management inprimary care: a decision analysis of competing strategies. Gas-troenterology 2002;122:1270–1285.

19. Talley NJ. Clinical management. Dyspepsia. Gastroenterology2003;125:1219–1226.

20. Koloski NA, Talley NJ, Boyce PM. Predictors of health careseeking for irritable bowel syndrome and nonulcer dyspepsia: acritical review of the literature on symptom and psychosocialfactors. Am J Gastroenterol 2001;96:1340–1349.

21. Owens DM, Nelson DK, Talley NJ. The irritable bowel syndrome:long-term prognosis and the physician-patient interaction. AnnIntern Med 1995;122:107–112.

22. Boekema PJ, Samsom M, Roelofs JMM, Smout AJPM. Effect ofcoffee on motor and sensory function of proximal stomach. DigDis Sci 2001;46:945–951.

23. Bortolotti M, Coccia G, Grossi G, Miglioli M. The treatment offunctional dyspepsia with red pepper. Aliment Pharmacol Ther2002;16:1075–1082.

24. Talley NJ. Functional dyspepsia: should treatment be targetedon disturbed physiology? Aliment Pharmacol Ther 1995;9:107–115.

25. Redstone HA, Barrowman N, Veldhuyzen Van Zanten SJ. H2-receptor antagonists in the treatment of functional (nonulcer)dyspepsia: a meta-analysis of randomized controlled clinicaltrials. Aliment Pharmacol Ther 2001;15:1291–1299.

26. Schwarz MP, Samsom M, van Berge Henegouwen GP, SmoutAJPM. Effect of inhibition of gastric acid secretion on antropylo-roduodenal motor activity and duodenal acid hypersensitivity infunctional dyspepsia. Aliment Pharmacol Ther 2001;15:1921–1928.

27. Corinaldesi R, Stanghellini V, Raiti C, Rea E, Salgemini R,Barbara L. Effect of chronic administration of cisapride on gas-tric emptying of a solid meal and on dyspeptic symptoms inpatients with idiopathic gastroparesis. Gut 1987;28:300–305.

28. Finney JS, Kinnersley N, Hughes M, O’Bryan-Tear CG, Lothian J.Meta-analysis of antisecretory and gastrokinetic compounds infunctional dyspepsia. J Clin Gastroenterol 1998;26:312–320.

29. Veldhuyzen van Zanten SJ, Jones MJ, Verlinden M, Talley NJ.Efficacy of cisapride and domperidone in functional dyspepsia:a meta-analysis. Am J Gastroenterol 2001;96:689–696.

30. Sturm A, Holtmann G, Goebell H, Gerken G. Prokinetics inpatients with gastroparesis: a systematic analysis. Digestion1999;60:422–427.

31. Degen L, Matzinger D, Merz M, Appel-Dingemanse S, OsborneS, Luchinger S, Bertold R, Maecke H, Beglinger C. Tegaserod, a5-HT4 receptor partial agonist, accelerates gastric emptyingand gastrointestinal transit in healthy male subjects. AlimentPharmacol Ther 2001;15:1745–1751.

32. Janssens J, Peeters TL, Vantrappen G, Tack J, Urbain JL, DeRoo M, Muls E, Bouillon R. Improvement of gastric emptying indiabetic gastroparesis by erythromycin. N Engl J Med 1990;332:1028–1031.








https://www.researchgate.net/publication/21402269_Acute_Helicobacter_pylori_infection_Clinical_features_local_and_systemic_immune_response_gastric_mucosal_histology_and_gastric_juice_ascorbic_acid_concentrations?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=





https://www.researchgate.net/publication/14075362_Kim_MS_Chey_WD_Owyang_C_Hasler_WL_Role_of_plasma_vasopressin_as_a_mediator_of_nausea_and_gastric_slow_wave_dysrhythmias_in_motion_sickness?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=






https://www.researchgate.net/publication/246702464_Effect_of_acid_perfusion_of_duodenum_on_induction_of_dyspeptic_symptoms_in_healthy_volunteers?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/271000694_Neostigmine-induced_increase_of_proximal_stomach_phasic_contraction_and_dyspeptic_symptoms_in_healthy_volunteers?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/13905756_Viral_gastroparesis_A_subgroup_of_idiopathic_gastroparesisclinical_characteristics_and_long-term_outcomes?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/13799226_Stress-induced_visceral_hypersensitivity_to_rectal_distension_in_rats_Role_of_CRF_and_mast_cells?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/13973397_Attention_and_distraction_Effects_on_gut_perception?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/14758951_Damgarrd_Pedersen_NE_Joelsson_B_Cimetidine_improves_GERD_symptoms_in_patients_selected_by_a_validated_GERD_questionnaire?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=








https://www.researchgate.net/publication/15217988_Empirical_H_SUB_2_Blocker_Therapy_or_Prompt_Endoscopy_in_Management_Of_Dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/13591947_First_line_treatment_with_omeprazole_provides_an_effective_and_superior_alternative_strategy_in_the_management_of_dyspepsia_compared_to_antacidalginate_liquid_A_multicentre_study_in_general_practice?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=






https://www.researchgate.net/publication/14001642_Lansoprazole_30_mg_daily_versus_ranitdine_150_mg_bd_in_the_treatment_of_acid-related_dyspepsia_in_general_practice?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=






https://www.researchgate.net/publication/223758137_Koloski_N_A_Talley_N_J_Boyce_P_M_Predictors_of_health_care_seeking_for_irritable_bowel_syndrome_and_nonulcer_dyspepsia_a_critical_review_of_the_literature_on_symptom_and_psychosocial_factors_Am_J_Gast?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/15206226_The_Irritable_Bowel_Syndrome_Long-Term_Prognosis_and_the_Physician-Patient_Interaction?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=


















https://www.researchgate.net/publication/19608830_Effect_of_chronic_administration_of_cisapride_on_gastric_emptying_of_a_solid_meal_on_dyspeptic_symptoms_in_patients_with_idiopathic_gastroparesis?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/13635795_Meta-Analysis_of_Antisecretory_and_Gastrokinetic_Compounds_in_Functional_Dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=






https://www.researchgate.net/publication/12826013_Prokinetics_in_Patients_with_Gastroparesis_A_Systematic_Analysis?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=











https://www.researchgate.net/publication/13710759_The_management_of_acid-related_dyspepsia_in_general_practice_a_comparison_of_an_omeprazole_versus_an_antacid-alginateranitidine_management_strategy_Complete_Research_Group?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=








https://www.researchgate.net/publication/289877447_Psychometric_scores_and_persistence_of_irritable_bowel_after_infectious_diarrhoea?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/284845831_Improvement_of_gastric_emptying_in_diabetic_gastroparesis_by_erythromycin?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1

1


33. Richards RD, Davenport K, McCallum RW. The treatment ofidiopathic and diabetic gastroparesis with acute intravenousand chronic oral erythromycin. Am J Gastroenterol 1993;88:203–207.

34. DiBaise JK, Quigley EM. Efficacy of prolonged administration ofintravenous erythromycin in an ambulatory setting as treatmentof severe gastroparesis: one center’s experience. J Clin Gas-troenterol 1999;28:131–134.

35. Talley NJ, Verlinden M, Snape W, Beker JA, Ducrotte P, DettmerA, Brinkhoff H, Eaker E, Ohning G, Miner PB, Mathias JR,Fumagalli I, Staessen D, Mack RJ. Failure of a motilin receptoragonist (ABT-229) to relieve the symptoms of functional dys-pepsia in patients with and without delayed gastric emptying: arandomized double-blind placebo-controlled trial. Aliment Phar-macol Ther 2000;14:1653–1661.

36. Verhagen MA, Samsom M, Maes B, Geypens BJ, Ghoos YF,Smout AJ. Effects of a new motilide, ABT-229, on gastric emp-tying and postprandial antroduodenal motility in healthy volun-teers. Aliment Pharmacol Ther 1997;11:1077–1086.

37. Tack J, Peeters T. What comes after macrolides and othermotilin stimulants? Gut 2001;49:317–318.

38. Tack J, Broeckaert D, Coulie B, Janssens J. The influence ofcisapride on gastric tone and the perception of gastric disten-sion. Aliment Pharmacol Ther 1998;12:761–766.

39. Tack J, Vos R, Janssens J, Salter J, Jauffret S, VandeplasscheG. Influence of tegaserod on proximal gastric tone and on theperception of gastric distention. Aliment Pharmacol Ther 2003;18:1–7.

40. Tack J, Delia T, Ligozio G, Sue S, Lefkowitz M, VandeplasscheG. A phase II placebo controlled randomized trial with tegaserodin functional dyspepsia patients with normal gastric emptying(abstr). Gastroenterology 2002;122:A154.

41. McColl K, Murray L, El-Omar E, Dickson A, El-Nujumi A, Wirz A,Kelman A, Penny C, Knill-Jones R, Hilditch T. Symptomaticbenefit from eradicating Helicobacter pylori infection in pa-tients with nonulcer dyspepsia. N Engl J Med 1998;339:1869–1874.

42. Blum AL, Talley NJ, O’Morain C, van Zanten SV, Labenz J, StolteM, Louw JA, Stubberod A, Theodors A, Sundin M, Bolling-Sternevald E, Junghard O. Lack of effect of treating Helicobacterpylori infection in patients with nonulcer dyspepsia. Omeprazoleplus Clarithromycin and Amoxicillin Effect One Year after Treat-ment (OCAY) Study Group [see comments]. N Engl J Med 1998;339:1875–1881.

43. Talley NJ, Janssens J, Lauritsen K, Racz I, Bolling-SternevaldE. Eradication of Helicobacter pylori in functional dyspepsia:randomised double blind placebo controlled trial with 12months’ follow up. The Optimal Regimen Cures HelicobacterInduced Dyspepsia (ORCHID) Study Group. BMJ 1999;318:833–837.

44. Talley NJ, Vakil N, Ballard ED II, Fennerty MB. Absence of benefitof eradicating Helicobacter pylori in patients with nonulcer dys-pepsia. N Engl J Med 1999;341:1106–1111.

45. McColl KE. Protagonist: should we eradicate Helicobacter pyloriin non-ulcer dyspepsia? Gut 2001;48:759–761.

46. Clouse RE. Antidepressants for functional gastrointestinal syn-dromes. Dig Dis Sci 1994;39:2352–2363.

47. Mertz H, Fass R, Kodner A, Yan-Go F, Fullerton S, Mayer EA.Effect of amitriptyline on symptoms, sleep, and visceral percep-tion in patients with functional dyspepsia. Am J Gastroenterol1998;93:160–165.

48. Tanum L, Malt UF. A new pharmacologic treatment of functionalgastrointestinal disorder. A double-blind placebo-controlledstudy with mianserin. Scand J Gastroenterol 1996;31:318–325.

49. Tack J, Broeckaert D, Coulie B, Fischler B, Janssens J. Influenceof the selective serotonin re-uptake inhibitor, paroxetine, on

gastric sensorimotor function in man. Aliment Pharmacol Ther2003;17:603–608.

50. Wu CY, Chou LT, Chen HP, Chang CS, Wong PG, Chen GH. Effectof fluoxetine on symptoms and gastric dysrhythmia in patientswith functional dyspepsia. Hepatogastroenterology 2003;50:278–283.

51. Gilja OH, Hausken T, Bang CJ, Berstad A. Effect of glyceryltrinitrate on gastric accommodation and symptoms in functionaldyspepsia. Dig Dis Sci 1997;42:2124–2131.

52. Sarnelli G, Sifrim D, Janssens J, Tack J. Influence of sildenafilon gastric sensorimotor function in man. Am J Physiol 2004 (inpress).

53. Gershon MD, Jonakait GM. Uptake and release of 5-hydroxytryp-tamine by enteric 5-hydroxytryptaminergic neurons: effects offluoxetine (Lilley 110140) and chlorimipramine. Br J Pharmacol1979;66:7–9.

54. Tack J, Coulie B, Wilmer A, Andrioli A, Janssens J. Effect ofsumatriptan on gastric fundus tone and on the perception ofgastric distension in man. Gut 2000;46:468–473.

55. Sarnelli G, Janssens J, Tack J. Effect of intranasal sumatriptanon gastric tone and sensitivity to distension. Dig Dis Sci 2001;46:1591–1595.

56. Tack J, Piessevaux H, Coulie B, Fischler B, De Gucht V, Jans-sens J. A placebo-controlled trial of buspirone, a fundus-relaxingdrug in functional dyspepsia: effect on symptoms and gastricsensory and motor function (abstr G1423). Gastroenterology1999;116:A325.

57. Thumshirn M, Camilleri M, Choi MG, Zinsmeister AR. Modula-tion of gastric sensory and motor functions by nitrergic andalpha2-adrenergic agents in humans. Gastroenterology 1999;116:573–585.

58. Talley NJ, Van Zanten SV, Saez LR, Dukes G, Perschyt T, HeathM, Kleoudis C, Mangel AW. A dose-ranging, placebo-controlled,randomized trial of alosetron in patients with functional dyspep-sia. Aliment Pharmacol Ther 2001;15:525–537.

59. Zerbib F, Bruley des Varannes S, Oriola RC, McDonald J, Isal JP,Galmiche JP. Alosetron does not affect the visceral perceptionof gastric distension in healthy subjects. Aliment PharmacolTher 1994;8:403–407.

60. Thompson CA. Alosetron withdrawn from market. Am J Health-Syst Pharm 2001;58:13.

61. Coffin B, Bouhassira D, Chollet R, Fraitag B, De Meynard C,Geneve J, Lemann M, Willer JC, Jian R. Effect of the kappaagonist fedotozine on perception of gastric distension in healthyhumans. Aliment Pharmacol Ther 1996;10:919–925.

62. Read NW, Abitbol JL, Bardhan KD, Whorwell PJ, Fraitag B.Efficacy and safety of the peripheral kappa agonist fedotozineversus placebo in the treatment of functional dyspepsia. Gut1997;41:664–668.

63. Delgado-Aros S, Hial HJ, Cremonini F, Ferber I, McKinzie S,Burton DD, Camilleri M. Effects of asimadoline, a kappa-opioidagonist, on satiation and postprandial symptoms in health.Aliment Pharmacol Ther 2003;18:507–514.

64. Biro T, Acs G, Acs P, Modarres S, Blumberg PM. Recent ad-vances in understanding of vanilloid receptors: a therapeutictarget for treatment of pain and inflammation in skin. J InvestDermatol Symp Proc 1997;2:56–60.

65. Lee KJ, Vos R, Tack J. Effects of capsaicin on the sensorimotorfunction of the proximal stomach in humans. Aliment PharmacolTher 2004;19:415–425.

66. Holtmann G, Adam B, Haag S, Collet W, Grunewald E, WindeckT. Efficacy of artichoke leaf extract in the treatment of patientswith functional dyspepsia: a six-week placebo-controlled, dou-ble-blind, multicentre trial. Aliment Pharmacol Ther 2003;18:1099–1105.

https://www.researchgate.net/publication/13211785_Efficacy_of_Prolonged_Administration_of_Intravenous_Erythromycin_in_an_Ambulatory_Setting_as_Treatment_of_Severe_Gastroparesis_One_Center's_Experience?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=











https://www.researchgate.net/publication/13620726_Effects_of_a_new_motilide_ABT-229_on_gastric_emptying_and_postprandial_antroduodenal_motility_in_healthy_volunteers?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=






https://www.researchgate.net/publication/13560060_The_influence_of_cisapride_on_gastric_tone_and_perception_of_gastric_distension?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=



https://www.researchgate.net/publication/13425036_Symptomatic_Benefit_from_Eradicating_Helicobacter_pylori_Infection_in_Patients_with_Nonulcer_Dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=





https://www.researchgate.net/publication/13425037_Lack_of_effect_of_treating_Helicobacter_pylori_infection_in_patients_with_nonulcer_dyspepsia_Omeprazole_plus_Clarithromycin_and_Amoxicillin_Effect_One_Year_after_Treatment_OCAY_Study_Group?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=







https://www.researchgate.net/publication/13199377_Eradication_of_H_pylori_in_functional_dyspepsia_randomised_double_blind_placebo_controlled_trial_with_12_months'_follow_up_The_Optimal_Regimen_Cures_Helicobacter_Induced_Dyspepsia_ORCHID_Study_Group?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=






https://www.researchgate.net/publication/12788091_Absence_of_Benefit_of_Eradicating_Helicobacter_pylori_in_Patients_with_Nonulcer_Dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=





https://www.researchgate.net/publication/15241842_Antidepressants_for_functional_gastrointestinal_syndrome?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=

https://www.researchgate.net/publication/15241842_Antidepressants_for_functional_gastrointestinal_syndrome?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=

https://www.researchgate.net/publication/13763118_Effect_of_Amitryptiline_on_Symptoms_Sleep_and_Visceral_Perception_in_Patients_With_Functional_Dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/14476740_A_New_Pharmacologic_Treatment_of_Functional_Gastrointestinal_Disorder_A_Double-Blind_Placebo-Controlled_Study_with_Mianserin?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=












https://www.researchgate.net/publication/13865012_Effect_of_Glyceryl_Trinitrate_on_Gastric_Accommodation_and_Symptoms_in_Functional_Dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=












https://www.researchgate.net/publication/284553403_A_placebo-controlled_trial_of_buspirone_a_fundus-relaxing_drug_in_functional_dyspepsia_Effect_on_symptoms_and_gastric_sensory_and_motor_function?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=









https://www.researchgate.net/publication/15212207_Alosetron_does_not_affect_the_visceral_perception_of_gastric_distension_in_healthy_subjects?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=






https://www.researchgate.net/publication/14237147_Effect_of_the_kappa_agonist_fedotozine_on_perception_of_gastric_distension_in_healthy_humans?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/13815228_Efficacy_and_safety_of_fedotozine_versus_placebo_in_the_treatment_of_functional_dyspepsia?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=








https://www.researchgate.net/publication/13744688_Recent_Advances_in_Understanding_of_Vanilloid_Receptors_A_Therapeutic_Target_for_Treatment_of_Pain_and_Inflammation_in_Skin?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=












https://www.researchgate.net/publication/14775731_Richards_R_D_Davenport_K_Mccallum_R_W_The_treatment_of_idiopathic_and_diabetic_gastroparesis_with_acute_intravenous_and_chronic_oral_erythromycin_Am_J_Gastroenterol_88_203-207?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/22824736_Uptake_and_release_of_5-hydroxytryptamine_by_enteric_serotonergic_neurons_Effects_of_fluoxetine_Lilly_110140_and_chlorimipramine?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=




https://www.researchgate.net/publication/240079264_Thumshirn_M_Camilleri_M_Choi_MG_et_al_Modulation_of_gastric_sensory_and_motor_functions_by_nitrergic_and_alpha2-adrenergic_agents_in_humans?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=








1

1

1

1

GGj


67. Bennett EJ, Piesse C, Palmer K, Badcock CA, Tennant CC,Kellow JE. Functional gastrointestinal disorders: psychological,social, and somatic features. Gut 1998;42:414–420.

68. Soo S, Moayyedi P, Deeks J, Delaney B, Lewis M, Forman D.Psychological interventions for non-ulcer dyspepsia. CochraneDatabase Syst Rev 2001;4:CD002301.

69. Hamilton J, Guthrie E, Creed F, Thompson D, Tomenson B, BennettR, Moriarty K, Stephens W, Liston R. A randomized controlled trialof psychotherapy in patients with chronic functional dyspepsia.Gastroenterology 2000;119:661–669.

70. Calvert EL, Houghton LA, Cooper P, Whorwell P. Long-termimprovement in functional dyspepsia using hypnotherapy. Gas-troenterology 2002;123:1778–1785.

Received November 20, 2003. Accepted May 6, 2004.Address requests for reprints to: Jan Tack, M.D., Ph.D., Division ofastroenterology, Department of Internal Medicine, University Hospitalasthuisberg, Herestraat 49, B-3000 Leuven, Belgium. e-mail:[email protected]; fax: (32) 16-34-44-19.

https://www.researchgate.net/publication/13707263_Functional_gastrointestinal_disorders_Psychological_social_and_somatic_features?el=1_x_8&enrichId=rgreq-b90bc833-0043-44f5-8d50-653eb5c2fe79&enrichSource=Y292ZXJQYWdlOzc3MTk3NjU7QVM6MTAzNDkxMDk5OTU1MjIyQDE0MDE2ODU2MTAxMDg=













Symptoms and Pathophysiological Correlations in Patients with Constipation and Functional Dyspepsia

Documents

Transcript of Symptoms and Pathophysiological Correlations in Patients with Constipation and Functional Dyspepsia