M. A. Van Herwaarden

The effect of baclofen on gastro-oesophageal reflux, lower oesophageal sphincter function and reflux symptoms in patients with reflux disease.

Background :u2002Baclofen decreases gastro‐oesophageal reflux episodes in healthy subjects by reducing the incidence of transient lower oesophageal sphincter relaxations.

Effect of different recumbent positions on postprandial gastroesophageal reflux in normal subjects

Abstract OBJECTIVE: Gastroesophageal reflux (GER) is increased in the right compared to the left recumbent position. Esophageal acid exposure is related to the acidity at the cardia, but the effect of body position on the acidity at the cardia has not yet been investigated. We aimed to investigate the mechanisms underlying increased esophageal acid exposure in the right recumbent position. METHODS: On 2 separate days a 4-h combined esophageal and lower esophageal sphincter (LES) manometry and pH recording of esophagus, gastric cardia, and corpus was performed in the right and left recumbent position after a high fat meal in 10 healthy subjects. RESULTS: In the right recumbent position a prolonged esophageal acid exposure (7.0% vs 2.0%, p CONCLUSIONS: Increased esophageal acid exposure in the right recumbent position relative to the left recumbent position is the result of a higher incidence of GER episodes caused by an increased incidence of TLESRs and higher percentage of TLESRs associated with GER. Body position does not affect the acidity at the gastric cardia and corpus.

The effect of Helicobacter pylori eradication on intragastric pH during dosing with lansoprazole or ranitidine

:u2002The antisecretory effect of omeprazole on intragastric pH is decreased in the absence of Helicobacter pylori.

Gastroesophageal Reflux Disease Is Associated With the C825T Polymorphism in the G-Protein β3 Subunit Gene (GNB3)

OBJECTIVES:Visceral hypersensitivity is involved in the etiology of reflux symptoms. Familial clustering and twin studies demonstrated a genetic predisposition to gastroesophageal reflux disease (GERD). G-protein-coupled receptors (GPCRs) mediate the response to acid, neurotransmitters and humoral factors modulating esophageal sensory function. Thus, polymorphisms in G-proteins are putative genetic factors contributing to GERD manifestation. A functional polymorphism in the G-protein β3 subunit gene (GNB3) is associated with functional dyspepsia (FD), in which visceral hypersensitivity is implicated in symptom generation. We evaluated the association of the GNB3 C825T polymorphism with GERD and GERD subgroups classified according to esophageal acid exposure time, symptom–reflux correlation, or coexistence of FD and/or irritable bowel syndrome (IBS) symptoms.METHODS:In total, 363 GERD patients, defined as having esophageal pH<4 ≥6% of time and/or symptom index (SI) ≥50% or symptom association probability (SAP) ≥95%, participated. In addition, 373 healthy controls free of gastrointestinal symptoms were studied. Genotyping was performed by molecular beacon assay.RESULTS:The CT genotype was more prevalent in GERD patients relative to healthy controls (adjusted odds ratio (OR)=1.43, 95% CI 1.04–1.98). GERD patients sensitive to physiological amounts of reflux displayed a higher OR (1.59), as did GERD patients with a positive symptom association score (1.50). The strongest association was detected in patients without concomitant FD and/or IBS symptoms (OR=1.66).CONCLUSIONS:GERD is associated with GNB3 C825T. The results for GERD subgroups support the hypothesis that enhanced perception of reflux events, as a consequence of the increased signal transduction upon GPCR activation associated with the 825T allele, underlies this association.

Effect of age on differences in upper esophageal sphincter and pharynx pressures between patients with dysphagia and control subjects.

OBJECTIVES:The aim of this study was to explore the effect of age and food consistency on manometric data of the swallow sequence in patients with dysphagia.METHODS:Manometric data from 41 patients (age range, 32–88 yr) and 41 age-matched control subjects was examined for differences between subgroups <60 yr and ≥60 yr of age, as well as for changes with food consistency.RESULTS:Only pharynx peak pressure showed an age-dependent decrease (144.1 ± 21.4 mm Hg vs 95.8 ± 15.1 mm Hg, p < 0.05) in patients. Significant higher upper esophageal sphincter residual pressure and delayed onset of upper esophageal sphincter relaxation were noted in patients aged <60 yr compared to age-matched controls, whereas only pharynx peak pressure was significantly lower in patients compared to controls aged ≥60 yr. Food consistency did not have a consistent effect on manometric results in patients with dysphagia.CONCLUSIONS:This is the first study to systematically explore the influence of age and food consistency on manometric parameters in dysphagia patients. These results may provide useful insights when identifying actual manometric abnormalities in patients with dysphagia. They also suggest possible different underlying mechanisms of dysphagia in younger versus older patients.

Persisting symptoms and decreased health-related quality-of-life in a cross-sectional study of treated achalasia patients

Little is known about symptom characteristics of treated achalasia patients and their effect on health‐related quality‐of‐life (HRQoL).

Validation of a disease-specific quality-of-life questionnaire in a large sample of Dutch achalasia patients.

SUMMARYnThe aim of this study was to validate a translated version of an achalasia-specific quality-of-life questionnaire (achalasia-DSQoL) by examining its psychometric properties in a Dutch cohort of achalasia patients. The achalasia-DSQoL was administered to 171 treated achalasia patients together with a clinical symptom score and the RAND-36. Validation methods included factor analysis, known-group techniques, Cronbachs alpha and Spearman rank correlation with other questionnaires and feasibility. About 72.5% of the achalasia patients completed the questionnaires. The achalasia-DSQoL showed evidence of an underlying construct and seems reliable with a Cronbachs alpha of 0.77. The question concerning heartburn did not correlate with the other items on the questionnaire. Known-group techniques demonstrated that the achalasia-DSQoL discriminates between achalasia patients in clinical remission and patients who are not. There was a moderate correlation between the achalasia-DSQoL and the RAND-36 subscales. The questionnaire was easy in use. The translated version of the achalasia-DSQoL is a valid and reliable instrument to compare groups of achalasia patients although the question concerning heartburn should be excluded.

In GERD patients, mucosal repair associated genes are upregulated in non‐inflamed oesophageal epithelium

Previous studies addressing the effects of acid reflux and PPI therapy on gene expression in oesophageal epithelium concentrated on inflamed tissue. We aimed to determine changes in gene expression in non‐inflamed oesophageal epithelium of GERD patients. Therefore, we included 20 GERD patients with pathological total 24‐hr acid exposure of 6–12% and SAP ≥ 95%. Ten patients discontinued PPI treatment (PPI‐), 10 took pantoprazole 40 mg bid (PPI+). Ten age/sex‐matched healthy controls were recruited. Biopsies were taken from non‐inflamed mucosa 6 cm and 16 cm proximal to the squamocolumnar junction (SCJ). Gene expression profiling of biopsies from 6 cm was performed on Human Genome U133 Plus 2.0 arrays (Affymetrix). Genes exhibiting a fold change >1.4 (t‐test P‐value < 1E– 4) were considered differentially expressed. Results were confirmed by real‐time RT‐PCR. In PPI‐ patients, 92 microarray probesets were deregulated. The majority of the corresponding genes were associated with cell–cell contacts, cytoskeletal reorganization and cellular motility, suggesting facilitation of a migratory phenotype. Genes encoding proteins with anti‐apoptotic or anti‐proliferative functions or stress‐protective functions were also deregulated. No probesets were deregulated in PPI+ patients. QPCR analysis of 20 selected genes confirmed most of the deregulations in PPI‐ patients, and showed several deregulated genes in PPI+ patients as well. In the biopsies taken at 16 cm QPCR revealed no deregulations of the selected genes. We conclude that upon acid exposure, oesophageal epithelial cells activate a process globally known as epithelial restitution: up‐regulation of anti‐apoptotic, anti‐oxidant and migration associated genes. Possibly this process helps maintaining barrier function.

Prolonged recording of oesophageal and lower oesophageal sphincter pressure using a portable water‐perfused manometric system

The aim of our study was to investigate the recording fidelity of a water‐perfused micromanometric catheter with incorporated sleeve combined with a newly developed portable water‐perfused manometric system for pharyngeal, oesophageal and lower oesophageal sphincter (LOS) pressure recording. The system’s performance was assessed in prolonged recordings in ambulant gastro‐oesophageal reflux disease (GORD) patients. Eighty 24‐h studies in GORD patients, carried out with the perfused portable manometric system, were evaluated. Twelve of these recordings were analysed in detail in order to compare oesophageal and LOS motor patterns with those described previously. Paired 2‐h manometric recordings of the pharynx, oesophagus, LOS and stomach, using the new system and a conventional perfused stationary manometric system, were performed in eight healthy subjects. With the portable manometric system oesophageal contractions, transient LOS relaxations, swallow‐associated prolonged LOS relaxations and LOS pressures were recorded with equal fidelity to the conventional manometric system. Recordings obtained with the portable system showed meal‐related and diurnal variations in oesophageal and LOS variables that were similar to these found in studies using conventional equipment. The new manometric system, consisting of a perfused micromanometric catheter with incorporated sleeve and a portable perfusion system, enables prolonged studies on oesophageal and LOS motor patterns in ambulant subjects.

Patients with physiological acid exposure and positive symptom association scores: a distinct group within the GORD spectrum

Abstractu2002 Studies comparing pH‐metrically well‐characterized gastro‐oesophageal reflux disease (GORD) patients with physiological reflux to GORD patients with pathological reflux, with regard to clinical and epidemiological data, are lacking. We included 273 GORD patients with pathological 24‐h pH‐monitoring (pH+), defined as pH<4u2003≥u20036% of time. A symptom index (SI)u2003≥u200350% was considered positive, as well as a symptom association probability (SAP)u2003≥u200395%. We included 84 GORD patients with physiological acid exposure (pH−) and a positive SI and/or SAP. Manometry and endoscopy reports were reviewed. Subjects completed questionnaires about demographics and medical history, functional dyspepsia and irritable bowel syndrome, the Nepean Dyspepsia Index symptom score and the RAND‐36 quality of life scale. pH− patients were younger (45 vs 50u2003years, Pu2003=u20030.003), more often female (60%vs 39%, Pu2003=u20030.001), smoked more (31%vs 19%, Pu2003=u20030.021) and reported proton pump inhibition failure more often (47%vs 32%, Pu2003=u20030.027). A hypotensive lower oesophageal sphincter was less common in pH− patients (18%vs 34%, Pu2003=u20030.008) and distal oesophageal contraction amplitude was higher (11 vs 9.5u2003kPa, Pu2003=u20030.045). pH− patients had hiatal hernia and oesophagitis less often (48%vs 73%, Pu2003<u20030.0005; 36%vs 54%, Pu2003=u20030.012 respectively). pH− patients less often reported no other symptoms besides GORD (20%vs 34%, Pu2003=u20030.015). pH− patients scored worse at the Nepean (reflux 19 vs 12 out of 39, Pu2003<u20030.0005; dyspepsia 54 vs 38 out of 156, Pu2003<u20030.0005). In the subgroup of patients who have physiological oesophageal acid exposure the enhancement of the perceived symptom burden appears to be the most important mechanism in GORD pathogenesis.