Characteristics associated with polypharmacy in people with type 2 diabetes: the Dutch Diabetes Pearl cohort.

AIM: To describe the prevalence and characteristics of polypharmacy in a Dutch cohort of individuals with type 2 diabetes. METHODS: We included people with type 2 diabetes from the Diabetes Pearl cohort, of whom 3886 were treated in primary care and 2873 in academic care (secondary/tertiary). With multivariable multinomial logistic regression analyses stratified for line of care, we assessed which sociodemographic, lifestyle and cardiometabolic characteristics were associated with moderate (5-9 medications) and severe polypharmacy (≥10 medications) compared with no polypharmacy (0-4 medications). RESULTS: Mean age was 63 ± 10 years, and 40% were women. The median number of daily medications was 5 (IQR 3-7) in primary care and 7 (IQR 5-10) in academic care. The prevalence of moderate and severe polypharmacy was 44% and 10% in primary care, and 53% and 29% in academic care respectively. Glucose-lowering and lipid-modifying medications were most prevalent. People with severe polypharmacy used a relatively large amount of other (i.e. non-cardiovascular and non-glucose-lowering) medication. Moderate and severe polypharmacy across all lines of care were associated with higher age, low educational level, more smoking, longer diabetes duration, higher BMI and more cardiovascular disease. CONCLUSIONS: Severe and moderate polypharmacy are prevalent in over half of people with type 2 diabetes in primary care, and even more in academic care. People with polypharmacy are characterized by poorer cardiometabolic status. These results highlight the significance of polypharmacy in type 2 diabetes.

Predictive Role of F2-Isoprostanes as Biomarkers for Brain Damage after Neonatal Surgery.

OBJECTIVE: Neonates have a high risk of oxidative stress during anesthetic procedures. The predictive role of oxidative stress biomarkers on the occurrence of brain injury in the perioperative period has not been reported before. METHODS: A prospective cohort study of patients requiring major surgery in the neonatal period was conducted. Biomarker levels of nonprotein-bound iron (NPBI) in plasma and F2-isoprostane in plasma and urine before and after surgical intervention were determined. Brain injury was assessed using postoperative MRI. RESULTS: In total, 61 neonates were included, median gestational age at 39 weeks (range 31-42) and weight at 3000 grams (1400-4400). Mild to moderate brain lesions were found in 66%. Logistic regression analysis showed a significant difference between plasma NPBI in patients with nonparenchymal injury versus no brain injury: 1.34 umol/L was identified as correlation threshold for nonparenchymal injury (sensitivity 67%, specificity 91%). In the multivariable analysis, correcting for GA, no other significant relation was found with the oxidative stress biomarkers and risk factors. CONCLUSION: Oxidative stress seems to occur during anaesthesia in this cohort of neonates. Plasma nonprotein-bound iron showed to be associated with nonparenchymal injury after surgery, with values of 1.34 umol/L or higher. Risk factors should be elucidated in a more homogeneous patient group.

Triage of colonoscopies: open access endoscopy versus outpatient consultation with a gastroenterologist.

BACKGROUND AND STUDY AIMS: In many Dutch hospitals, open access referral for colonoscopy is authorized by a gastroenterologist after screening a standard referral letter (SRL) without face-to-face contact with the patient. We investigated the added value of a 7.5 min outpatient consultation with a gastroenterologist (OC), regarding the patient indications, priority for colonoscopy, and the frequency of correct information about patient medications and comorbidities on SRLs. PATIENTS AND METHODS: In a prospective, blinded, single-center study, gastroenterologists assessed SRLs for the accuracy and priority of the colonoscopy request (SRL). These data were compared to results from the OC, and primary outcomes were the number of patients who were not recommended for colonoscopy and priority scheduling of colonoscopy for suspicion of cancer. RESULTS: Patients were analyzed using both SRL and OC and, of 255 patients, 224 of them underwent colonoscopy. Colonoscopy was not recommended for 6.3 % and 11.4 % of patients using the SRL and OC, respectively (P = 0.02). Using the SRL, gastroenterologists did not recommend colonoscopy for seven patients, but the same patients were recommended for colonoscopy when OC was available. This was explained because the indications on the SRL did not match the information obtained from OC. Compared to OC , more colonoscopies were prioritized when the SRL was used to make decisions. Cancer was detected in 7/112 (SRL ) versus 7/65 (OC ) of priority-scheduled patients. SRLs did not report the use of coumarins and insulin in 1.6 % of patients or the prevalence of serious comorbid conditions in 52 % of patients. CONCLUSIONS: A 7.5 min outpatient consultation with a gastroenterologist improved the identification of indications for colonoscopy, decreased priority scheduling of patients, and increased the number of patients diagnosed with cancer in the prioritized group. SRLs frequently omitted patients' medications and comorbidities.

Severe hepatitis with coagulopathy due to HSV-1 in an immunocompetent man.

Severe hepatitis due to herpes simplex virus type 1 (HSV-1) in immunocompetent patients is a very rare event. The acute hepatitis may lead to fulminant deterioration of liver function and can be rapidly fatal. The diagnosis should be considered in case of severe hepatitis of unknown cause. Early consideration of HSV-1 hepatitis in the differential diagnosis in an adult patient, also with an apparently normal immune system, is important and early initiation of antiviral treatment may be lifesaving in this situation.

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 > or = 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 < 1(E)- 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.

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

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<4 > or = 6% of time. A symptom index (SI) > or = 50% was considered positive, as well as a symptom association probability (SAP) > or = 95%. 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 50 years, P = 0.003), more often female (60%vs 39%, P = 0.001), smoked more (31%vs 19%, P = 0.021) and reported proton pump inhibition failure more often (47%vs 32%, P = 0.027). A hypotensive lower oesophageal sphincter was less common in pH- patients (18%vs 34%, P = 0.008) and distal oesophageal contraction amplitude was higher (11 vs 9.5 kPa, P = 0.045). pH- patients had hiatal hernia and oesophagitis less often (48%vs 73%, P < 0.0005; 36%vs 54%, P = 0.012 respectively). pH- patients less often reported no other symptoms besides GORD (20%vs 34%, P = 0.015). pH- patients scored worse at the Nepean (reflux 19 vs 12 out of 39, P < 0.0005; dyspepsia 54 vs 38 out of 156, P < 0.0005). 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.

Gastroesophageal reflux disease is associated with the C825T polymorphism in the G-protein beta3 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 beta3 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 > or = 6% of time and/or symptom index (SI) > or = 50% or symptom association probability (SAP) > or = 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.

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

SUMMARY: The 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, Cronbach's 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 Cronbach's 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.

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

BACKGROUND: Little is known about symptom characteristics of treated achalasia patients and their effect on health-related quality-of-life (HRQoL). AIMS: To examine clinical remission, achalasia-associated symptoms and HRQoL in treated achalasia patients. METHODS: The Eckardt clinical symptom score, RAND-36 and a disease-specific HRQoL questionnaire were sent to 171 treated achalasia patients. RESULTS: 76.6% of the patients returned their questionnaire. 44.9% of them were not in symptomatic remission. Prevalence of frequent dysphagia (at least daily) and chest pain (at least weekly) was 46% and 38%, respectively. Achalasia patients had lower general HRQoL scores than control subjects (all RAND-36 subscales, except health change; P < or = 0.002). Patients with frequent symptoms of chest pain and dysphagia showed lower HRQoL than patients with less frequent symptoms on three RAND-36 subscales (pain, social functioning and general health perceptions; P < 0.003). Patients in clinical remission showed higher HRQoL than patients who were not, however HRQoL in the 'remission group' remained significantly impaired as compared to controls (all RAND-36 subscales except emotional role limitations and mental health; P < 0.001). CONCLUSIONS: Many achalasia patients remain severely symptomatic after treatment and have decreased HRQoL. Frequent symptoms are associated with lower HRQoL. Patients in clinical remission show substantially improved, but not restored HRQoL.

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

BACKGROUND: Baclofen decreases gastro-oesophageal reflux episodes in healthy subjects by reducing the incidence of transient lower oesophageal sphincter relaxations. AIM: To investigate the effect of baclofen on reflux symptoms, oesophageal pH and lower oesophageal sphincter manometry in patients with gastro-oesophageal reflux disease. METHODS: A double-blind, placebo-controlled, two-way crossover design was used to study the effect of baclofen on heartburn and regurgitation 3 h after a provocation test meal in 37 patients with gastro-oesophageal reflux disease. Additionally, in 20 of these patients, the effect of baclofen on oesophageal pH, transient lower oesophageal sphincter relaxations and basal lower oesophageal sphincter pressure was studied. RESULTS: Baclofen significantly decreased the acid reflux time and the incidence of gastro-oesophageal reflux episodes (8.3 +/- 8.8% vs. 12.4 +/- 12.0%, P = 0.03 and 10.9 +/- 7.3 per 3 h vs. 18.7 +/- 12.4 per 3 h). The incidence of transient lower oesophageal sphincter relaxations was significantly lower with baclofen than with placebo (15.1 +/- 6.4 per 3 h vs. 22.8 +/- 5.4 per 3 h, P < 0.0001). Lower oesophageal sphincter pressure and the percentage of transient lower oesophageal sphincter relaxations associated with reflux were not affected by baclofen. No significant effect on symptom scores was observed. CONCLUSIONS: Baclofen decreases post-prandial acid reflux in patients with gastro-oesophageal reflux disease by reducing the incidence of transient lower oesophageal sphincter relaxations. No effect of a single dose of baclofen on reflux symptoms could be demonstrated in this 3-h post-prandial study.

Prolonged manometric recordings of oesophagus and lower oesophageal sphincter in achalasia patients.

BACKGROUND AND AIMS: Conventional short term manometry is a valuable tool in the diagnosis of achalasia but the technique may fail to detect intermittent motor events. The aim of this study was to investigate the pattern of lower oesophageal sphincter (LOS) and oesophageal pressures during prolonged recording in patients with achalasia. METHODS: Eleven patients with idiopathic achalasia were studied. Prolonged combined oesophageal pH and manometric recordings of the pharynx, LOS, and stomach were performed using a pH glass electrode and a multiple lumen assembly incorporating a Dent sleeve connected to a portable water perfused manometric system. RESULTS: LOS pressure varied during the day. Postprandial LOS pressures were lower than those recorded preprandially (1.2 v 1.8 kPa; p=0.005) and basal LOS pressures were significantly higher during phase III of the migrating motor complex than during the subsequent phase I (3.3 v 1.8 kPa; p=0.028). Complete LOS relaxations were occasionally observed in seven patients (0.48/h). Complete LOS relaxations were longer in duration than incomplete LOS relaxations (10.8 v 2.8 s; p=0.01) and 57% of complete relaxations fulfilled the criteria of a transient LOS relaxation (TLOSR). Complete LOS relaxations were associated with oesophageal pressure waves with higher amplitudes and longer durations. In addition, a higher proportion of these oesophageal pressure waves were spontaneous (55.6% v 0%; p<0.02) and multipeaked (72.7% v 0%). During prolonged manometry, high amplitude oesophageal pressure waves (>10 kPa) were recorded in six patients and retrograde oesophageal pressure waves in four, phenomena which were not observed during short term manometry. CONCLUSION: In contrast with short term stationary manometry, prolonged manometry in achalasia patients revealed the occurrence of complete LOS relaxations, TLOSRs, variations in LOS pressure associated with a meal or phase III, and high amplitude and retrograde oesophageal pressure waves.

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.

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 > or = 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 > or = 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.

Computer analysis of prolonged lower oesophageal sphincter pressure recordings.

The aim of the study was to validate a recently developed computer program for the analysis of prolonged recordings of lower oesophageal sphincter pressure. Thirty 1-hour stretches were selected from sets of 24-h pressure signals recorded from the pharynx, oesophagus, lower oesophageal sphincter (LOS) and stomach in 10 ambulant patients with gastrooesophageal reflux disease. Three experienced investigators visually analysed end-expiratory LOS pressures and transient lower oesophageal sphincter relaxations (TLOSRs), using published criteria. A computer program was developed for calculation of an end-expiratory pressure curve and detection of TLOSRs using the same criteria. Although the results showed an maximum deviation from the mean of 11.1% and 14.8% for manually calculated LOS pressures and visually detected TLOSRs, respectively only 62.1% of the detected TLOSRs were detected by all three observers. LOS pressure as measured by the computer closely approximated the mean of the LOS pressures calculated by the three observers. Although the total number of TLOSRs was comparable to that assessed by visual analysis, the computer detected only 46% of the TLOSRs detected by each observer and 56.8% of the TLOSRs detected by all observers. It is concluded that automated calculation of end-expiratory LOS pressure is feasible and yields reliable results, whereas automated detection of TLOSRs could not be satisfactorily accomplished. Our study showed that improvement of computer algorithms for TLOSR detection is desirable. However, the previously described criteria for detection of TLOSRs are insufficiently precise; further refinement of these criteria will be necessary to reduce the large discrepancies between the outcome of detection of TLOSRs by computer and by humans, and to reduce the equally large discrepancies between the results of detection by different human observers.

Excess gastroesophageal reflux in patients with hiatus hernia is caused by mechanisms other than transient LES relaxations.

BACKGROUND & AIMS: Esophageal acid exposure is higher in gastroesophageal reflux disease (GERD) patients with hiatus hernia than in those without. We investigated the effect of a sliding hiatus hernia on the mechanisms underlying spontaneous gastroesophageal reflux over 24 hours. METHODS: Twelve GERD patients with and 10 GERD patients without hiatus hernia were studied for 24 hours. Combined esophageal pH and manometric recordings of the pharynx, lower esophageal sphincter (LES), and stomach were performed using a multiple-lumen assembly incorporating a Dent sleeve connected to a portable water-perfused manometric system and a pH glass electrode. RESULTS: Patients with hiatus hernia had greater esophageal acid exposure (7.6% vs. 3.3%; P < 0.01) and more reflux episodes (3.1 vs. 1.8/h; P < 0.001) than those without. LES pressure, the incidence of transient LES relaxations (TLESRs), and the proportion of TLESRs associated with acid reflux were comparable in both groups. Both groups had equal numbers of reflux episodes associated with TLESRs and swallow-associated prolonged LES relaxations. Patients with hiatus hernia had more reflux associated with low LES pressure, swallow-associated normal LES relaxations, and straining during periods with low LES pressure. CONCLUSIONS: The excess reflux in GERD patients with hiatus hernia compared with those without is caused by malfunction of the gastroesophageal barrier during low LES pressure, swallow-associated normal LES relaxations, deep inspiration, and straining.

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

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 < 0.03), a higher incidence of reflux episodes (3.8 vs 0.9/h, p < 0.03), more transient LES relaxations (TLESRs) (6.5 vs 3.2/h, p < 0.03), and higher percentage TLESRs associated with reflux (57.0% vs 22.4% p < 0.03) was recorded than in the left supine position. Acidity at gastric cardia and corpus was not affected by body position. 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.

Diagnosis of reflux disease.

There are numerous tests for which a diagnostic value in the context of gastro-oesophageal reflux disease has been claimed. Some of these tests (e.g. the acid perfusion test) have become obsolete after the advent of 24-hour oesophageal pH monitoring. With the latter test not only can excessive reflux be identified, but also, and more importantly, a temporal relationship can be demonstrated between a patient's symptoms and reflux episodes. Radiographical examination of the oesophagus has largely been replaced by endoscopy, although the use of the former test is still indicated in certain circumstances (e.g. in the differentiation of sliding from para-oesophageal hiatus hernia). In clinical practice, the so-called proton pump inhibitor test has gained considerable popularity. Despite several studies on the specificity and sensitivity of this test, its value has not yet been established with sufficient accuracy. Conventional manometric evaluation of lower oesophageal sphincter pressure has been over-emphasized as a diagnostic test in gastro-oesophageal reflux disease.

The effect of motilin agonist ABT-229 on gastro-oesophageal reflux, oesophageal motility and lower oesophageal sphincter characteristics in GERD patients.

BACKGROUND: ABT-229, a motilin agonist without antibacterial activity, has been shown to enhance both lower oesophageal sphincter pressure in cats and gastric emptying in humans. AIM: To investigate the effect of oral treatment with ABT-229 10 mg b.d., ABT-229 5 mg b. d. and cisapride 10 mg q.d.s. on gastro-oesophageal reflux, lower oesophageal sphincter pressure, transient lower oesophageal sphincter relaxations and symptoms in GERD patients. METHODS: Twenty-four GERD patients completed the study. A randomized, double-blind, placebo-controlled, three-period incomplete crossover design was used with three dosing periods of 7 days. All patients received ABT-229 10 mg b.d. and placebo during two of the three periods. In the remaining period 12 patients were given ABT-229 5 mg b.d. and 12 received cisapride 10 mg q.d.s. Ambulatory 24 h recordings of oesophageal pH and pharyngeal, oesophageal, lower oesophageal sphincter and gastric pressures were performed on day 7 using an assembly incorporating a Dent sleeve connected to a portable water-perfused manometric system. RESULTS: Oesophageal acid exposure was not affected by ABT-229 or cisapride, but the incidence of reflux episodes was reduced by cisapride. None of the drugs affected oesophageal motility, lower oesophageal sphincter pressure or the incidence of transient lower oesophageal sphincter relaxations. Both ABT-229 10 mg b.d. and cisapride reduced the severity of daytime heartburn. CONCLUSION: The value of ABT-229 in the treatment of GERD appears to be limited.

24-h recording of intragastric pH: technical aspects and clinical relevance.

BACKGROUND: Information about gastric acid secretion and gastric acidity can be obtained using several techniques but, presently, continuous intragastric pH recording is probably the one applied most frequently. This paper aims to review the technical aspects and some important applications of intragastric pH monitoring in research and clinical practice. METHODS: Literature review. RESULTS: Most studies on intragastric pH are performed with either glass or antimony electrodes. Optimal measurement of 24-h intragastric pH requires accurate calibration of the pH measuring system, exact positioning of the pH electrodes, and a sufficient sample rate. Depending on the aim of the study the results of intragastric pH monitoring are expressed either as median H+ activity or as median pH values. Gastric acidity shows a circadian rhythm, modified by buffering meals and nocturnal duodenogastric reflux. In health, age, gender and smoking habits are known to influence gastric acidity. In duodenal ulcer disease an increased gastric acidity is found and in patients with gastric ulcer gastric acidity is decreased. In GERD, no relation between reflux oesophagitis and gastric acidity is found. Helicobacter pylori affects intragastric pH most pronounced during acid inhibitory therapy, both in DU patients and in healthy subjects. In the absence of H. pylori the effect of proton-pump inhibitors on intragastric pH is much less than in the presence of the microorganism, whereas the effect of ranitidine on intragastric pH is barely affected by the H. pylori status. CONCLUSIONS: Despite some limitations, intragastric pH monitoring provides important information about gastric acidity.