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Biomedical subjects

W Schwizer

Publications and source records attributed to W Schwizer.

At least 19 recordsLinked to original sources

The effects of tegaserod on oesophageal function and bolus transport in healthy volunteers: studies using concurrent high-resolution manometry and videofluoroscopy.

BACKGROUND: Tegaserod is a partial 5-hydroxytryptamine 4 receptor agonist with prokinetic effects on the gastrointestinal tract, its effects on oesophageal function are unknown. AIM: A randomized, placebo controlled, double-blind trial assessed the effect of tegaserod on the oesophagus in healthy, asymptomatic subjects. METHOD: A 7-day course of tegaserod 6 mg b.d. vs. placebo was prescribed (n = 17/21 completed both phases of study). High-resolution manometry and pH measurements were performed before and after a test meal. Bolus transport of liquids and solids was studied by high-resolution manometry and videofluoroscopy. RESULTS: Tegaserod had no effect on lower oesophageal sphincter pressure compared with placebo, peristaltic velocity increased (P < 0.001) and distal contractile pressure decreased slightly (P < 0.05). Transient lower oesophageal sphincter relaxations and reflux were infrequent regardless of treatment. During the studies of bolus transport, high-resolution manometry revealed that tegaserod promoted mid-oesophageal contractility (P < 0.02) and shortened the 'proximal transition zone' (P < 0.05), the level where bolus escape occurred most frequently. These effects had no effect on liquid bolus transport; however a non-significant trend to improved solid bolus transport was observed (66% vs. 31%;P = 0.07). CONCLUSION: Tegaserod did not alter lower oesophageal sphincter pressure, but had significant effects on peristaltic function. High-resolution manometry promoted mid-oesophageal contractility during bolus transport. This effect was associated with a non-significant trend to improved solid bolus transit.

Adult↗

[Functional magnetic resonance imaging of the gastrointestinal tract--clinical application possibilities?].

Magnetic resonance imaging (MRI) is a versatile medical imaging tool for which several new applications have been developed. Beside its broad clinical use for the detection of anatomical structures and pathologies MRI has been successfully applied for the non-invasive imaging of human organ functions, including the brain and the cardiovascular system. The use of MRI for the assessment and analysis of gastrointestinal (GI) function is a new approach that is currently performed in only a few research sites. Several characteristics make MRI an ideal technique for the direct assessment of GI physiology: MRI acquires high resolution images with excellent soft tissue contrast, it does not expose subjects to ionizing radiation, is non-invasive, and the acquisition and analysis of the images can be independently verified. In this article we summarize recent developments of MRI techniques in GI research. We will also discuss the advantages and limitations of MRI for this purpose in relation to established medical imaging tools and investigations.

Forecasting↗

The pathophysiology of faecal spotting in obese subjects during treatment with orlistat.

BACKGROUND: The intermittent loss of oil or liquid faeces ('spotting') is an adverse effect that occurs in obese patients during treatment with the lipase inhibitor orlistat; the pathophysiology is unknown. AIM: To investigate the effects of orlistat on anorectal sensorimotor function and continence. METHODS: Obese subjects susceptible to spotting were identified by an unblind trial of orlistat. Obese spotters (n = 15) and non-spotters (n = 16) completed a randomized, double-blind, cross-over trial of orlistat and placebo. Anorectal function was assessed by rectal barostat and anal manometry, together with a novel stool substitute retention test, a quantitative measurement of faecal continence. RESULTS: Orlistat increased stool volume and raised faecal fat and water. Treatment had no effect on anorectal motor function, but rectal sensation was reduced; on retention testing, the volume retained was increased. Subjects susceptible to spotting had lower rectal compliance, heightened rectal sensitivity and weaker resting sphincter pressure than non-spotters. On retention testing, gross continence was maintained; however, spotters lost small volumes of rectal contents during rectal filling. CONCLUSION: Treatment with orlistat has no direct adverse effects on anorectal function or continence. Spotting occurs during treatment with orlistat when patients with sub-clinical anorectal dysfunction are exposed to increased stool volume and altered stool composition.

Adult↗

High-resolution manometry predicts the success of oesophageal bolus transport and identifies clinically important abnormalities not detected by conventional manometry.

BACKGROUND AND AIMS: High-resolution manometry (HRM) is a recent development in oesophageal measurement; its value in the clinical setting remains a matter of controversy. (i) We compared the accuracy with which bolus transport could be predicted from conventional manometry and HRM. (ii) The clinical value of HRM was assessed in a series of patients with endoscopy-negative dysphagia in whom conventional investigations had been non-diagnostic. METHOD: (i) Control subjects and patients with endoscopy-negative dysphagia underwent concurrent HRM and video-fluoroscopy. Ninety-five records were reviewed using HRM with spatiotemporal plot and conventional line plots of the pressure data derived from the same recording. (ii) The HRM and notes of patients with endoscopy-negative dysphagia and abnormal bolus transport were analysed to identify additional information provided by the new technique. RESULTS: (i) Receiver operating characteristic analysis demonstrated that HRM predicts the presence of abnormal bolus transport more accurately than conventional manometry. (ii) HRM identified clinically important motor dysfunction not detected by manometry and radiography. These included localized disturbances of peristalsis and abnormal movement of the lower oesophageal sphincter during oesophageal spasm. CONCLUSION: The HRM predicts bolus movement more accurately than conventional manometry and identifies clinically relevant oesophageal dysfunction not detected by other investigations including conventional manometry.

Adult↗

Analysis of the meal-dependent intragastric performance of a gastric-retentive tablet assessed by magnetic resonance imaging.

BACKGROUND: Modern medical imaging modalities can trace labelled oral drug dosage forms in the gastrointestinal tract, and thus represent important tools for the evaluation of their in vivo performance. The application of gastric-retentive drug delivery systems to improve bioavailability and to avoid unwanted plasma peak concentrations of orally administered drugs is of special interest in clinical and pharmaceutical research. AIM: To determine the influence of meal composition and timing of tablet administration on the intragastric performance of a gastric-retentive floating tablet using magnetic resonance imaging in the sitting position. METHODS: A tablet formulation was labelled with iron oxide particles as negative magnetic resonance contrast marker to allow the monitoring of the tablet position in the food-filled human stomach. Labelled tablet was administered, together with three different solid meals, to volunteers seated in a 0.5-T open-configuration magnetic resonance system. Volunteers were followed over a 4-h period. RESULTS: Labelled tablet was detectable in all subjects throughout the entire study. The tablet showed persistent good intragastric floating performance independent of meal composition. Unfavourable timing of tablet administration had a minor effect on the intragastric tablet residence time and floating performance. CONCLUSION: Magnetic resonance imaging can reliably monitor and analyse the in vivo performance of labelled gastric-retentive tablets in the human stomach.

Adult↗

Experimental model of continent colostomy using rectus abdominis neosphincteroplasty.

BACKGROUND: Use of dynamic myoplasty to create a continent stoma has produced promising results, but long-term stoma continence has not been achieved. The aim of the study was to establish and test a new model. METHODS: Three types of dynamic rectus abdominis sphincteroplasty around a colostomy and two conditioning protocols were tested in ten domestic pigs. Continence was assessed by means of conventional defaecography and neosphincter manometry after 8 and 12 weeks. The neosphincter muscle was studied histologically to assess the transformation of muscle type. RESULTS: Use of a distal rectus muscle sling surrounding the stoma by 270 degrees with a low-frequency conditioning protocol achieved a continent colostomy for more than 12 h on each of 5 consecutive days. The neosphincter had a 40-mm high-pressure segment with mean pressure of 74 (range 67-82) mmHg. The proportion of type I muscle fibres increased from 38 (range 32-42) to 74 (range 66-78) per cent after 12 weeks of conditioning. CONCLUSION: This pilot study demonstrated the feasibility of a continent stoma in an animal model with a dynamic rectus neosphincter. Long-term results should be confirmed in a larger series before use in humans can be considered.

Animals↗

Glucose control is not improved by accelerating gastric emptying in patients with type 1 diabetes mellitus and gastroparesis. a pilot study with cisapride as a model drug.

The present pilot study investigated whether acceleration of gastric emptying in patients with type 1 diabetes and delayed gastric emptying (a possible cause of poorly controlled diabetes) improves long-term glucose control. Eight outpatients with diabetes (age 28-63 years, mean diabetes duration 24.6+/-6.0 years) and delayed gastric emptying of radio-opaque markers were randomised and treated, for three months each, with a prokinetic drug (cisapride 20 mg twice daily) and placebo. Mean capillary glucose, glucose variability (M-values, MAGE), fructosamine, and HbA1c were assessed. Gastric emptying of a solid standard meal was measured by scintigraphy after each treatment period. Chronic administration of a prokinetic drug resulted in improved solid gastric emptying (percentage residual) at 120 min (p=0.025). The percentage residual was 43.6+/-9.6 % during prokinetic treatment and 59.7+/-9.9 % during placebo (standard error of paired differences 5.7 %). The mean gastric emptying time (t/2) of solids was 88 min during prokinetic treatment compared to 113 min in the placebo arm (SE of paired differences 14 min; p=0.09). Mean blood glucose values (9.0+/-3.8 vs. 8.8+/-3.7 mmol/l), daily glucose variability (MAGE 6.8+/-1.3 vs. 6.3+/-1.6 mmol/l; M-value 15.2+/-2.5 vs. 13.9+/-4.5), and HbA1c at 3 months (7.8+/-1.1 % vs. 7.6+/-1.0 %) were not statistically different between prokinetic drug and placebo treatment. Similarly, the frequency of hypoglycaemic episodes (< or = 3 mmol/l) was not different in both groups (78 vs. 68). Our pilot study showed that long-term acceleration of gastric emptying had no effect on overall glycaemic control, the magnitude of glucose excursions, and hypoglycaemic episodes in patients with diabetic gastroparesis. We do not recommend, therefore, acceleration of gastric emptying as treatment strategy for "brittle diabetes" in patients with type 1 diabetes.

Adult↗

Non-invasive investigation of gastrointestinal functions with magnetic resonance imaging: towards an "ideal" investigation of gastrointestinal function.

Gastrointestinal (GI) function is complex and physiological measurements are subject to a variety of technical difficulties and practical limitations. The ideal technique would be non-invasive, widely available, convenient, and reliable and would not expose the subject to ionising radiation. It would permit direct assessment of GI function in the postprandial as well as the resting state, and be able to differentiate between food, secretion, and air in the lumen. GI structure and function are interdependent and the ideal technique would permit simultaneous assessment of these factors. Finally, the bowel operates as a functional whole and assessment of the GI tract proximal and distal to the area of interest is desirable. In this article the authors summarise the development and validation of magnetic resonance imaging techniques that overcome many of the deficiencies of existing methods, and have many characteristics of the "ideal" investigation of GI function.

Defecation↗

Demonstration of acid secretion in the gastric pouch through the pentagastrin stimulation test.

INTRODUCTION: The aim of this study is to determine the relationship of hydrochloric acid secretion in gastric pouch (GP), an orthotopic neobladder using a stomach segment, to gastrin. MATERIAL AND METHOD: Pentagastrin (PG) stimulation test (PGST) was applied in 10 patients who had had GP surgery 5-70 months ago, and their urinary pH changes in the next 2 h were observed. RESULTS: Significant pH decreases (from 6.6 +/- 0.6 to 2.9 +/- 1.0 in the mean) 30-75 min after injection of PG, demonstrating gastrin-triggered acid secretion in GP were observed in all patients. The pH values were normalized in 2 h (6.6 +/- 1.0 in the mean). CONCLUSION: In PGST, urinary pH decreases, demonstrating the close relationship between gastrin release and acid secretion in the GP. Inhibition of gastrin by any means may be useful in keeping the urinary pH on physiological levels.

Aged↗

Effects of meal consistency and ingested fluid volume on the intragastric distribution of a drug model in humans--a magnetic resonance imaging study.

BACKGROUND: Controlled delivery of drugs to the small intestine in relation to emptying of an ingested meal is important in various pathophysiological conditions. We investigated the effects of different food consistencies and the amount of co-ingested liquid on the intragastric distribution of a contrast marker. METHODS: Five healthy subjects received four meals (each 650 kcal: A, mashed potato with 100 mL water; B, rice with 100 mL water; C, hamburger meal with 100 mL water; D, hamburger meal with 300 mL water). A capsule filled with gadolinium tetra-azacyclododecane tetra-acetic acid solution (as contrast marker) was ingested following meal termination, and its intragastric distribution was assessed by magnetic resonance imaging. RESULTS: Initially, marker distribution was confined to the fundus, and subsequently extended along the inner curvature of the stomach. The maximum distribution volume of the marker was lower in meal A than in meal B (P < 0.05). No differences in marker distribution were observed when the hamburger meal was given with 100 or 300 mL water. CONCLUSIONS: The intragastric distribution kinetics of the marker gadolinium tetra-azacyclododecane tetra-acetic acid appeared to depend on meal consistency, but not on the amount of water co-ingested. Three-dimensional magnetic resonance imaging allows detailed analysis of the intragastric distribution of a drug model in relation to meal emptying and intragastric meal distribution.

Adult↗

Non-invasive measurement of gastric accommodation in humans.

Gastric accommodation describes the reduction in gastric tone and increase in compliance that follows ingestion of a meal and involves at least two responses: "receptive relaxation" which allows the stomach to accept a volume load without a significant rise in gastric pressure and "adaptive relaxation" which modulates gastric tone in response to the specific properties of the meal ingested. However, there are considerable technical difficulties in measuring the accommodation process. The current standard barostat studies, and other methods such as conventional and three dimensional ultrasound, or single photon emission computed tomography have significant disadvantages. Preliminary findings from the development and validation of a new magnetic resonance imaging technique that addresses many of the deficiencies of previous methods are presented.

Adaptation, Physiological↗

Helicobacter pylori and symptomatic relapse of gastro-oesophageal reflux disease: a randomised controlled trial.

BACKGROUND: There is little information on the effects of Helicobacter pylori eradication in patients with a primary diagnosis of gastro-oesophageal reflux disease (GORD). Our aim was to investigate the effect of H pylori eradication in this group of patients. METHODS: We did a double-blind, randomised, placebo-controlled study in 70 patients with GORD. We assigned individuals to three groups. All patients received lansoprazole 30 mg twice daily for 10 days, followed by 30 mg once daily for 8 weeks. Patients infected with H pylori received either antibiotics (clarithromycin 500 mg and amoxicillin 1000 mg twice daily) or placebo for the first 10 days. Controls were patients not infected with H pylori. Patients were followed up for 6 months at 2-week intervals for GORD symptoms. At the end of the study we repeated endoscopy and oesophageal and gastric 24 h-pH monitoring. FINDINGS: 58 of 70 patients completed our study. At the end of the study 16 of these patients were H pylori-positive (14 placebo and two eradication failures), 13 were negative because of successful H pylori eradication, and 29 were controls. H pylori-positive patients relapsed earlier (54 days) than did those in whom H pylori was eradicated (100 days) (p=0.046). The H pylori-negative control group relapsed after the longest period (110 days). However, time to relapse was also affected by oesophagitis grade (no oesophagitis 127 days, grade III or IV oesophagitis 18 days). When results were corrected for the affect of oesophagitis grade, H pylori-positive patients relapsed earlier (p=0.086) than H pylori-eradiated patients and controls (p=0.001). INTERPRETATION: H pylori infection positively affects the relapse rate of GORD. Eradication of H pylori could, therefore, help to prolong disease-free interval in patients with GORD.

2-Pyridinylmethylsulfinylbenzimidazoles↗

Monitoring the intragastric distribution of a colloidal drug carrier model by magnetic resonance imaging460.

PURPOSE: Monitoring the distribution of drugs or drug delivery systems in the human gastrointestinal tract is an important prerequisite for the design of orally administered drugs. We investigated the intragastric distribution of a colloidal drug delivery system (liposomes containing the contrast agent Gd-DOTA) by magnetic resonance imaging. METHODS: Following ingestion of a liquid or a solid meal, gastric distribution of liposomes released from a capsule and the fat component of the solid meal were tracked in 7 healthy subjects for 90 min. Liposomes were identified in gastric content by the increased signal intensity provided by the encapsulated Gd-DOTA. RESULTS: With the liquid meal, liposomes initially formed a layer on the surface before distributing in 86 +/- 2% of gastric content (maximum distribution volume) within 42 +/- 6 min. With the solid meal, maximum distribution (7 +/- 1%, reached within 24 +/- 6 min) was confined to a small volume in the fundus without forming a layer, suggesting that distribution was related to the accessible liquid compartment. Fat distribution was inhomogeneous and concentrated in the fundus. CONCLUSIONS: Intragastric distribution of a colloidal drug carrier model, such as Gd-DOTA-filled liposomes, varies between meals of different composition. These differences can be monitored in three dimensions in humans by MRI.

Adult↗

Pressure-geometry relationship in the antroduodenal region in humans.

Understanding of the control mechanisms underlying gastric motor function is still limited. The aim of the present study was to evaluate antral pressure-geometry relationships during gastric emptying slowed by intraduodenal nutrient infusion and enhanced by erythromycin. In seven healthy subjects, antral contractile activity was assessed by combined dynamic magnetic resonance imaging and antroduodenal high-resolution manometry. After intragastric administration of a 20% glucose solution (750 ml), gastric motility and emptying were recorded during intraduodenal nutrient infusion alone and, subsequently, combined with intravenous erythromycin. Before erythromycin, contraction waves were antegrade (propagation speed: 2.7 +/- 1.7 mm/s; lumen occlusion: 47 +/- 14%). Eighty-two percent (51/62) of contraction waves were detected manometrically. Fifty-four percent of contractile events (254/473) were associated with a detectable pressure event. Pressure and the degree of lumen occlusion were only weakly correlated (r(2) = 0.02; P = 0.026). After erythromycin, episodes of strong antroduodenal contractions were observed. In conclusion, antral contractions alone do not reliably predict gastric emptying. Erythromycin induces strong antroduodenal contractions not necessarily associated with fast emptying. Finally, manometry reliably detects ~80% of contraction waves, but conclusions from manometry regarding actual contractile activity must be made with care.

Duodenum↗