Maria Mangano

Effect of increasing the fat content but not the energy load of a meal on gastro-oesophageal reflux and lower oesophageal sphincter motor function

Background—Although fatty foods are commonly considered detrimental in patients with reflux disease, no objective data exist that substantiate this belief. Aims—To investigate the effect of fat on gastro-oesophageal reflux and lower oesophageal sphincter (LOS) motor activity. Subjects—Thirteen healthy subjects and 14 patients with reflux disease. Methods—Oesophageal pH, LOS, and oesophageal pressures were recorded for 180 minutes after a high fat (52% fat) and a balanced (24% fat) meal (both 3.18 MJ) on two different occasions. Eight controls and seven patients were studied in the recumbent position and the others in the sitting position. Results—The percentage of time at pH less than 4 and the rate of reflux episodes were higher (p<0.01) in the patients than in the healthy subjects (mean 14.1% versus 1.7% and 4.4/h versus 0.8/h respectively), as was the percentage of transient LOS relaxations associated with reflux (62% versus 32%, p<0.01). The high fat meal did not increase the rate of reflux episodes nor exposure to oesophageal acid in either group regardless of body posture.The rate of transient LOS relaxations, their association with reflux, and basal LOS pressure were also unaffected. Conclusions—Increasing fat intake does not affect gastro-oesophageal reflux or oesophagogastric competence for at least three hours after a meal.

Effect of Calories and Fat on Postprandial Gastro-oesophageal Reflux

Background: Gastro-oesophageal reflux (GOR) is commonly considered to be worsened by fatty food, but it has recently been shown that changing the fat content of equicaloric meals has no effect on GOR over a 3-h postprandial period. Our aims were to verify this finding over a longer postprandial period and test the hypothesis that increasing the caloric content of balanced meals increases GOR. Methods: Thirteen healthy subjects (6 men) aged 19-31 years underwent 6-h oesophageal pH monitoring after 3 solid/liquid meals of the same volume and osmolarity eaten on separate days in a randomized order: a) high fat (58% fat) 2.8 MJ; b) balanced (23% fat) 2.8 MJ; and c) balanced low calorie (25% fat) 1.6 MJ. Results: The mean percentage of time at pH < 4 and the mean number of reflux episodes after the balanced 2.8 MJ meal (3.0% and 11.5, respectively) were higher ( P < 0.05) than after the balanced 1.6 MJ meal (1.6% and 7.2) and similar to those after the equicaloric (2.8 MJ) high-fat meal (2.5% and 9.3). Acid clearance time was similar after all three meals. Conclusions: Our data suggest that advice on dietary habits in patients with GOR disease should be concentrated on decreasing the caloric load of meals rather than their fat content.

Relationship between motor function of the proximal stomach and transient lower oesophageal sphincter relaxation after morphine

Background: Morphine reduces the rate of transient lower oesophageal sphincter (LOS) relaxations but its site of action is presently unknown. There are no data available concerning its motor effects on the proximal stomach, an important site for triggering transient LOS relaxations. Aim: To evaluate the effect of morphine on the rate of transient LOS relaxations and motor function of the proximal stomach. Subjects and methods: In 19 healthy subjects, concurrent transient LOS relaxations with a sleeve sensor and motor function of the proximal stomach with a bag connected to an electronic barostat were recorded during pressure controlled (n = 9) and volume controlled (n = 10) gastric distensions after intravenous administration of placebo and morphine 100 μg/kg. Results: During pressure controlled distensions, intrabag volume was markedly decreased by morphine (median 189 ml (interquartile range 101–448) v 404 (265–868) after placebo; p<0.01) as was the rate of transient LOS relaxations (0.5/30 minutes (0.4–2) v 2.5 (2–4); p<0.01). When intrabag volume was kept constant (525 ml (490–600)) (that is, in volume controlled distensions), the rate of transient LOS relaxations was not affected by morphine (2/30 minutes (2–3) v 2.5 (2–3)). Gastric contractions decreased after morphine similarly during pressure controlled and volume controlled distensions (8.5/30 minutes (4–10) v 15.5 (9.5–20.5), p<0.02; and 6.5 (0–24) v 19.5 (12–22), p<0.05). Conclusions: The effect of morphine on transient LOS relaxations is dependent on the decrease in volume of the proximal stomach. Our data suggest that pharmacological interventions which decrease fundal volume should result in control of transient LOS relaxation mediated gastro-oesophageal reflux.

Multiple rapid swallowing in idiopathic achalasia: evidence for patients' heterogeneity.

Abstract  In order to evaluate the function of inhibitory neural pathways in achalasia, we compared the response of the oesophageal body and lower oesophageal sphincter (LOS) to single swallows (SS) and multiple rapid swallowing (MRS) in 20 consecutive patients with untreated idiopathic achalasia (10 men, aged 23–81 years) and in 20 control patients without dysphagia (nine men, aged 31–73 years), using sleeve manometry; 277 SS and 85 MRS were analysed. In the control group, MRS inhibited motor activity in the oesophageal body and induced a slightly lower (P < 0.05) nadir LOS pressure compared with SS. In the achalasia patients, MRS induced a variable response: eight patients had simultaneous motor activity during all MRS although onset was delayed compared with SS [median (interquartile range), 3.5 s (1.7–6.1) vs 1.4 s (0.8–3.9); P < 0.05], whereas eight patients showed motor inhibition which occurred during all MRS in four of them, and the remaining four had no motor activity both after SS and during MRS. Overall MRS did not decrease nadir LOS pressure compared with SS [12 mmHg (5–20) vs 16 mmHg (7–22); P > 0.1]; however, it induced complete LOS relaxation in three of the patients. MRS gives further evidence of functional heterogeneity among achalasia patients.

Fat and esophageal sensitivity to acid

The hypothesis that fat increases esophageal sensitivity to acid was tested in eight patients with gastroesophageal reflux disease and 11 healthy subjects. Protocol 1 included randomized intragastric infusions of saline or Lipofundin S 20% (306 kcal) on two separate days, followed after 30 and 90 min by an 8 ml/min intraesophageal infusion of 0.1 N HCl. The time to the onset of heartburn and the maximum heartburn score by visual analog scale during the acid infusion were similar after intragastric saline (2 min and 29.5 mm, medians) and fat (2 min and 20.5 mm). Protocol 2 included two 8 ml/min intraesophageal infusions of 0.2 N HCl diluted in an equal volume of saline or Lipofundin S 20% at a time interval of 10 min in randomized order. The time to the onset of heartburn and the maximum heartburn score were unaffected by the presence of fat in the esophageal infusate (2.5 min and 53 mm without vs 1.5 min and 49 mm with fat). We conclude that fat does not increase esophageal sensitivity to acid.

Long-term effects of pneumatic dilatation on symptoms and lower oesophageal sphincter pressure in achalasia.

Background: Pneumatic dilatation is an effective treatment for achalasia. Although follow-up studies have shown that its clinical benefit persists for years, it is still unknown whether the decrease in lower oesophageal sphincter (LOS) pressure is maintained over time. Our aim is to assess the long-term effects of pneumatic dilatation on symptoms and LOS pressure in patients with idiopathic achalasia. Methods: Eleven consecutive patients with achalasia (7 men) underwent 1 ( n = 5) or 2 ( n = 6) pneumatic dilatations (Rigiflex dilator) in order to achieve a stable (> 1 year) clinical remission. Clinical scores (0-12, with scores of h 3 indicating remission) and LOS pressure (sleeve manometry) were determined before treatment, after 3 and 12 months, and then every year for 6 years. Results: No operative complications occurred. The patients showed a marked clinical improvement (2.0 (2.0-2.0), median (IQ range), after 3 months versus 8.0 (7.2-9.0) before treatment; P < 0.001), which was maintained throughout the follow-up period. Concurrently, there was a marked decrease in LOS pressure (5.0 (4.0-7.0) mmHg after 3 months versus 25.0 (20.0-36.2) before treatment; P < 0.001), which also remained stable over time. Conclusions: One or two pneumatic dilatations induce stable clinical remission and a decrease in LOS pressure that remains unchanged over time. Our data further support the use of dilatations as first-line treatment of achalasia.

Composition dependent separation of oligonucleotides by capillary electrophoresis in acidic buffers with application to the quality control of synthetic oligonucleotides

Abstract Oligonucleotides have become a widely used tool in molecular biology and molecular diagnostics. Their parallel synthesis in large numbers has raised the request for fast and informative analytical tools for their quality control. Here we propose an alternative to current analytical methodologies based on capillary electrophoresis at very low pH in free solution. In these non-classical analytical conditions oligonucleotides can be discriminated for their base composition, thus adding a further dimension to the classical electrophoretic sizing performed in sieving media at moderately basic pH. We have tested several separating conditions at various pH values on a very large set of samples (about 200 synthetic oligonucleotides) ranging from 10 to 50 residues and with different terminal modification including amine, phosphate, biotin, fluorescein and other fluorescent dyes. We have been able to characterize the quality of these synthetic products and to detect base redundancies (i.e. the copresence of different bases in a single position of the oligonucleotide chain) in oligonucleotides up to 50 bases long, thus posing the basis for the application of this method to the emerging field of detection mutation in complex genomes analysis.

Endoscopic sealing of a rectovesical fistula with a combination of an over the scope clip and cyano-acrylate injection

The risk of anastomotic fistula after colon resection is currently reported to range from 5% to 10%. If the fistula is symptomatic or pauci-symptomatic the best therapy is a diverting ileostomy for 2-3 months with subsequent recanalization only when a radiological contrast study shows that the fistula has disappeared (1). Recently, technological advances in gastrointestinal accessories have led to the development of a novel type of clip, the over the scope (OVESCO®) clip, currently used for organ closure during natural orifice transluminal endoscopic surgery (NOTES) (2), or in particular cases of bleeding of the gastrointestinal tract (3) or deep wall lesions (4).

Effect of loperamide on gastro-oesophageal reflux.

BACKGROUND We have recently shown that morphine reduces gastro-oesophageal reflux (GOR) by stimulating opioid receptors. Our aim was therefore to investigate the effect of loperamide, a peripheral opioid agonist, on GOR. METHODS Nine patients with GOR disease underwent two ambulatory 24-h intra-oesophageal pH monitoring sessions separated by a period of at least 7 days under double-blind randomized conditions during the administration of placebo or loperamide solution p.o. (8 mg + 4 mg + 4 mg, 12 h and 2 h before, and 7 h after the start of the recording). RESULTS Twenty-four-hour oesophageal acid exposure and the number of reflux episodes/hour were similar under the two experimental conditions: a median (IQ range) of 6.2% (3.3%-11.0%) of the time at pH < 4 and 2.6 (1.6-3.5)/h during placebo versus 8.8% (3.7%-14.8%) and 2.8 (2.3-4.9)/h during loperamide (P = ns). Acid clearance time was also similar: 1.8 +/- 0.3 min versus 1.6 +/- 0.2 min (P = ns). CONCLUSIONS Loperamide did not decrease GOR, thus suggesting that an opioid agonist may not be useful in the treatment of GOR disease.

Multiple rapid swallowing in idiopathic achalasia: from conventional to high resolution manometry. Authors' reply

Dear Editors, We thank Dr Fox for his interest in our work on multiple rapid swallowing (MRS). High resolution manometry (HRM) represents an advance in intraluminal pressure recording and we look forward to seeing further observations on MRS using this technique, which will probably characterize and differentiate patients with achalasia more precisely than conventional manometry. Regarding possible ‘lower oesophageal sphincter (LOS) pseudorelaxation’, we do not think that swallow induced oesophageal shortening is an important confounding factor of LOS relaxation as assessed by the sleeve sensor in achalasia patients, because HRM has already shown axial movement of the LOS region to occur infrequently and conventional methods of detecting incomplete LOS relaxation to perform well in this patients’ population (Staiano and Clouse, AJG 2001; 96: 3258–67). D. Savojardo, M. Mangano, P. Cantù & R. Penagini Cattedra di Gastroenterologia, University of Milan, Fondazione IRCCS Ospedale Maggiore, Mangiagalli, Regina Elena, Milan, Italy e-mail: roberto.penagini@unimi.it