Reliability of oesophageal pH recording for the detection of gastro-oesophageal reflux

Objective. Despite the new gold standard oesophageal impedance monitoring, pH monitoring is still used frequently for detection of gastro-oesophageal reflux (GOR). Besides drops in pH from above to below pH4, drops of ≥1 unit are also used as a marker for GOR. In this study the objective was to investigate the accuracy of drops in pH for detection of GOR, using impedance monitoring as the gold standard. Material and methods. Nineteen GORD patients (9 M, 55±11 years) underwent combined 24-h pH-impedance recording off acid-suppressive therapy. All drops in pH ≥0.5 pH units, with a duration ≥4 s, reaching the nadir pH within 5 s after onset were included. Reflux events detected with impedance monitoring were taken as the reference. Results. In total, 2221 drops in pH were found; 47% were acid (nadir pH <4), 47% weakly acidic (nadir pH between pH7 and 4) and 5% were superimposed (pH drop starting below pH4). The sensitivities of acid, weakly acidic and superimposed pH drops ≥1 were 91%, 28%, 24%, respectively, and the percentages of false-positive reflux episodes were 20, 56 and 54, respectively. Acid reflux with a cut-off ≥0.5 and ≤3.3 had a moderate-to-good sensitivity (94–70%) and low false-positive percentages (23–13%). In contrast, weakly acidic and superimposed reflux showed greater false-positive than true-positive percentages for all cut-off values. Conclusions. Compared to impedance monitoring, detection of reflux with pH monitoring is clearly inferior. When drops in pH ≥1 are used irrespective of nadir pH as an indicator of reflux episodes, the number of reflux episodes is overestimated. Decreases from above to below 4 with cut-offs between ≥0.5 and ≤3.3 are the most indicative of true reflux episodes.     

Effect of proximal gastric volume on hiatal hernia

Background Spatial separation of the diaphragm and the lower esophageal sphincter (LES) occurs frequently and intermittently in patients with a sliding hiatus hernia and favors gastro‐esophageal reflux. This can be studied with high‐resolution manometry. Although fundic accommodation is associated with a lower basal LES pressure, its effect on esophagogastric junction configuration and hiatal hernia is unknown. Therefore, the aim of this study was to investigate the relationship between proximal gastric volume, the presence of a hiatal hernia profile and acid reflux. Methods Twenty gastro‐esophageal reflux disease (GERD) patients were studied and compared to 20 healthy controls. High‐resolution manometry and pH recording were performed for 1 h before and 2 h following meal ingestion (500 mL per 300 kcal). Volume of the proximal stomach was assessed with three‐dimensional ultrasonography before and every 15 min after meal ingestion. Key Results During fasting, the hernia profile [2 separate high‐pressure zones (HPZs) at manometry] was present for 31.9 ± 4.9 min h^?1 (53.2%) in GERD patients, and 8.7 ± 3.3 min h^?1 (14.5%) in controls (P < 0.001). In GERD patients, the presence of hernia profile decreased during the first postprandial hour to 15.9 ± 4.2 min h^?1, 26.5%, P < 0.01 whilst this phenomenon was not observed in controls. The rate of transition between the two profiles was 5.7 ± 1.1 per hour in GERD patients and 2.5 ± 1.0 per hour in controls (P < 0.001). The pre and postprandial acid reflux rate in GERD patients during the hernia profile (6.4 ± 1.1 per hour and 18.4 ± 4.3 per hour respectively) was significantly higher than during reduced hernia (2.1 ± 0.6 per hour; P < 0.05 and 3.8 ± 0.9 per hour; P < 0.05). A similar difference was found in controls. Furthermore, an inverse correlation was found between fundic volume and the time the hernia profile was present (r = ?0.45; P < 0.05) in GERD patients, but not in controls. Conclusions & Inferences (i) In GERD patients a postprandial increase in proximal gastric volume is accompanied by a decrease in hernia prevalence, which can be explained by a reduction of the intra‐thoracic part of the stomach. (ii) A temporal hernia profile also occurs in healthy subjects. (iii) During the hernia profile, acid reflux is more prevalent, especially after meal ingestion.     

Endoscopic gastroplication for the treatment of gastro-oesophageal reflux disease: a randomised, sham-controlled trial

BACKGROUND: Endoscopic treatment for gastro-oesophageal reflux disease (GORD) is rapidly emerging, but there is a great need for randomised controlled trials to evaluate the efficacy. DESIGN AND SETTING: A single-centre, double-blind, randomised, sham-controlled trial of endoscopic gastroplication by the Endocinch suturing system. Patients and INTERVENTIONS: 60 patients with GORD were randomly assigned to three endoscopic gastroplications (n = 20), a sham procedure (n = 20) or observation (n = 20). The research nurse and patients in the active and sham groups were blinded to the procedure assignment. After 3 months, open-label active treatment was offered to all patients. OUTCOME MEASURES: The primary outcome measures were proton pump inhibitor (PPI) use and GORD symptoms, and secondary measures were quality of life, 24-h oesophageal acid exposure, oesophageal manometry and adverse events. Follow-up assessments were performed at 3, 6 and 12 months. RESULTS: At 3 months, the percentage of patients who had reduced drug use by > or =50% was greater in the active treatment group (65%) than in the sham (25%) or observation groups (0%) (p<0.02). Symptoms (heartburn and to a lesser extent regurgitation) improved more in the active group than in the sham group. Three Short Form-20 quality of life subscales (role function, general health and bodily pain perception) improved in the active group versus sham. Oesophageal acid exposure was modestly decreased after active treatment (p<0.02), but not significantly greater than after the sham procedure (p = 0.61). The active treatment effects on PPI use, symptoms and quality of life persisted after 6 and 12 months of open-label follow-up (n = 41), but 29% of patients were retreated in this period. No serious adverse events occurred. CONCLUSIONS: Endoscopic gastroplication, using the Endocinch device, reduced acid-inhibitory drug use, improved GORD symptoms and improved the quality of life at 3 months compared with a sham procedure. The effects persisted up to 12 months. However, the reduction in oesophageal acid exposure was not greater after endoscopic treatment than after a sham procedure.     

Revisiting the immunomodulators tacrolimus, methotrexate, and mycophenolate mofetil: their mechanisms of action and role in the treatment of IBD

Inflammatory bowel diseases (IBDs) are thought to result from unopposed immune responses to normal gut flora in a genetically susceptible host. A variety of immunomodulating therapies are applied for the treatment of patients with IBDs. The first-line treatment for IBDs consists of 5-aminosalicylate and/or budesonide. However, these first-line therapies are often not suitable for continuous treatment or do not suffice for the treatment of severe IBD. Recently, efforts have been made to generate novel selective drugs that are more effective and have fewer side effects. Despite promising results, most of these novel drugs are still in a developmental stage and unavailable for clinical application. Yet, another class of established immunomodulators exists that is successful in the treatment of inflammatory bowel diseases. While waiting for emerging novel therapies, the use of these more established drugs should be considered. Furthermore, one of the advantages of using established immunomodulators is the well-documented knowledge on the long-term side effects and on the mechanisms of action. In this review, the authors discuss 3 well-known immunomodulators that are being applied with increased frequency for the treatment of IBD: tacrolimus, methotrexate, and mycophenolate mofetil. These agents have been used for many years as treatment modalities for immunosuppression after organ transplantation, for the treatment of cancer, and for immunomodulation in several other immune-mediated diseases. First, this review discusses the potential targets for immunomodulating therapies in IBDs. Second, the immunomodulating mechanisms and effects of the 3 immunomodulators are discussed in relationship to these treatment targets.     

Lower Bifidobacteria counts in both duodenal mucosa-associated and fecal microbiota in irritable bowel syndrome patients

AIM： To determine the composition of both fecal and duodenal mucosa-associated microbiota in irritable bowel syndrome （IBS） patients and healthy subjects using molecular-based techniques.
METHODS： Fecal and duodenal mucosa brush samples were obtained from 41 IBS patients and 26 healthy subjects. Fecal samples were analyzed for the composition of the total microbiota using fluorescent in situ hybridization （FISH） and both fecal and duodenal brush samples were analyzed for the composition of bifidobacteria using real-time polymerase chain reaction.
RESULTS： The FISH analysis of fecal samples revealed a 2-fold decrease in the level of bifidobacteria （4.2 ± 1.3 vs 8.3 ± 1.9, P 〈 0.01） in IBS patients compared to healthy subjects, whereas no major differences in other bacterial groups were observed. At the species level, Bifidobacterium catenulatum levels were significantly lower （6 ± 0.6 vs 19 ± 2.5, P 〈 0.001） in the IBS patients in both fecal and duodenal brush samples than in healthy subjects.
CONCLUSION： Decreased bifidobacteria levels in both fecal and duodenal brush samples of IBS patients compared to healthy subjects indicate a role for microbiotic composition in IBS pathophysiology.     

Small bowel motility affects glucose absorption in a healthy man

OBJECTIVE: To investigate the relationship between duodenojejunal motor activity and glucose absorption and to evaluate the effect of modification of duodenojejunal motility on glucose absorption by using the prokinetic drug cisapride. RESEARCH DESIGN AND METHODS: We examined seven healthy males, mean age 22 years, who were treated with cisapride 10 mg t.i.d. and placebo during 3 days in a randomized order, with a 2-week time interval. Duodenojejunal manometry was performed after each treatment on the morning of day 3, using an 18-lumen catheter. A liquid nutrient (3 kcal/min) was administered intraduodenally for 30 min, followed by a bolus of the glucose analog 3-O-methylglucose (3-OMG). Plasma 3-OMG concentrations were measured to assess absorption kinetics. RESULTS: The area under the 3-OMG concentration curve in the first 30 min after infusion was related to the number of antegrade propagated pressure waves (r = 0.49, P < 0.05), but not to the peak concentration, time to peak, and absorption fraction. The mean amplitude of pressure waves was higher during cisapride than placebo (P < 0.05), but the reoccurrence of interdigestive motility, numbers of pressure waves, and propagated pressure waves, as well as 3-OMG absorption characteristics, were not significantly different between the two treatments. During both treatments >60% of antegrade propagated pressure waves were propagated over a very short distance (1.5 cm). CONCLUSIONS: Glucose absorption in the human small intestine is related to short-traveling propagated intestinal contractile activity. Cisapride increases the amplitude of pressure waves, but does not affect the organization of pressure waves or the absorption of 3-OMG.     

Muscle power development in preterm infants with periventricular flaring or leukomalacia in relation to outcome at 18 months

Periventricular flaring (PVF) or periventricular leukomalacia (PVL) was diagnosed by brain ultrasound during the neonatal period in 44 infants (34 males, 10 females; mean gestational age 31 weeks 2 days, SD 2 weeks 1 day) admitted between 1995 and 1997. The infants were divided into three groups according to the severity of their condition. At 0, 3, and 6 months' corrected age an age-adequate neurological examination with special emphasis on the relation between active and passive muscle power was performed and symmetry between right and left sides was assessed. Results for the whole body, as well as for the shoulders, trunk, and legs were classified as optimal, suspect, or abnormal. Motor outcome at 18 months' corrected age was graded in the same way. An overall optimal muscle power regulation was found in one infant at 0, two at 3, and one at 6 months. Suspect outcome was found at all ages in the three groups. At 0 months muscle power regulation did not differ between the three groups. At 3 and 6 months overall poor muscle power, primarily caused by poor muscle power regulation in the shoulders and trunk, was found in infants with PVL grades III or IV. At 18 months' corrected age 24 infants showed no neurological impairment, eight infants had minor impairment, and 12 infants had severe impairment, including all 10 infants categorized as having PVL grades II or IV. The best predictors of impairment at 18 months were the combined results of muscle power in the shoulders and trunk at 3 months with those of the shoulders at 6 months.     

Relationships of upper gastrointestinal motor and sensory function with glycemic control

Acute changes in the blood glucose concentration have a major reversible effect on esophageal, gastric, intestinal, gallbladder, and anorectal motility in both healthy subjects and diabetic patients. For example, gastric emptying is slower during hyperglycemia than euglycemia and accelerated during hypoglycemia. Acute hyperglycemia also affects perceptions arising from the gastrointestinal tract and may accordingly, be important in the etiology of gastrointestinal symptoms in diabetes. Elevations in blood glucose that are within the normal postprandial range also affect gastrointestinal motor and sensory function. Upper gastrointestinal motor function is a critical determinant of postprandial blood glucose concentrations by influencing the absorption of ingested nutrients. Interventions that reduce postprandial hyperglycemia, by modulating the rate of gastric emptying, have the potential to become mainstream therapies in the treatment of diabetes.