Gastric emptying of glucose solution and associated plasma concentrations of GLP-1, GIP, and PYY before and after fundoplication.

BACKGROUND: This study was designed to assess the relationship between gastric emptying of glucose solution and the ensuing plasma concentrations of glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and glucose-dependent insulinotropic polypeptide (GIP) in patients having undergone fundoplication for gastroesophageal reflux (GERD). SUBJECTS AND METHODS: In 10 male patients the emptying of 50% glucose solution was determined scintigraphically and its relationship with plasma glucose, GLP-1, PYY, and GIP concentrations was studied before and 3 months after fundoplication. RESULTS: In the first 30 min after glucose ingestion, emptying was significantly (p = 0.048) faster after fundoplication than before. Emptying and GLP-1 and GIP correlated: the faster the emptying during the first 30 min the greater the concentrations integrated over that period (p = 0.04; p = 0.01; p = 0.02). Emptying and PYY concentrations were unrelated. In the 120-180 min. period, blood glucose concentrations were lower the faster the emptying in the initial 30 min (p = 0.06) and the entire 50-min recording period (p = 0.03) had been. The GLP-1 concentrations integrated over the first 30 min correlated inversely with the integrated plasma glucose during the third hour after ingestion (p = 0.004). CONCLUSIONS: After fundoplication, gastric emptying may, if accelerated in its initial phases, give rise to greater and earlier increases in plasma glucose, GLP-1, and GIP concentrations and thus to reactive hypoglycemia.

[Esophageal 24 hour-pH metry. Recommendations of the German Society of Neurogastroenterology and Motility and the Study Group for Gastrointestinal Functional Disorders and Function Diagnostics of the Austrian Society of Gastroenterology and Hepatology]. / 24-Stunden-Osophagus-pH-Metrie. Empfehlungen der Deutschen Gesellschaft für Neurogastroenterologie und Motilität und der Arbeitsgruppe für gastrointestinale Funktionsstörungen und Funktionsdiagnostik der Osterreichischen Gesellschaft für Gastroenterologie und Hepatologie.

This article presents the recommendations for 24-hour oesophageal pH-metry of the German Society of Neurogastroenterology and Motility and the Study Group for Gastrointestinal Functional Disorders and Function Diagnostics of the Austrian Society of Gastroenterology and Hepatology. Indications for the examination, the procedures to be followed, the analysis of the obtained data and the conclusions to be drawn are delineated. The literature on which the recommendations are based is reviewed.

[Nissen and Toupet laparoscopic fundoplication in patients with gastroesophageal reflux and motility disorders of the distal esophagus]. / Laparoskopische Fundoplicatio nach Nissen und Toupet bei Patienten mit gastroösophagealer Refluxkrankheit und Motilitätsstörung des distalen Osophagus.

INTRODUCTION: A Nissen fundoplication for gastrooesophageal reflux disease may more often lead to persistent dysphagia than a Toupet fundoplication. The aim of this study was to assess the results of laparoscopic Nissen versus Toupet fundoplication in patients with reflux disease and impaired distal esophageal motility. PATIENTS AND METHODS: In 15 patients a laparoscopic Nissen and in 17 a laparoscopic Toupet fundoplication was carried out. Criteria for an impaired motility of the distal esophagus were a mean amplitude of < 30 mm Hg of swallow-induced contractions, or > 33% non-propulsive or non-transmitted contraction waves. Before surgery, heartburn, dysphagia, regurgitation and other symptoms were scored and endoscopic, manometric and 24 hour pH-metric investigations performed. Patients were reinvestigated 3 to 30 (median 15) months after Nissen and 3 to 42 (median 7) months after Toupet fundoplication. RESULTS: After Nissen as well as after Toupet fundoplication heartburn was significantly less frequent, whereas dysphagia and all other symptom-scores remained unchanged. In the 26 patients reinvestigated manometrically, the resting pressure of the lower esophageal sphincter was significantly higher following both operations and the residual sphincter pressure upon swallowing higher only after Nissen fundoplication. The amplitude of swallow-induced contractions and the percentages of non-propulsive and non-transmitted contraction waves were not significantly changed after either operation. In the 23 patients restudied pH-metrically, reflux activity was significantly reduced after both Nissen and Toupet fundoplication. CONCLUSION: In patients with reflux disease and impaired distal esophageal motility, laparoscopic Nissen and Toupet fundoplication both yielded satisfactory results and neither operation led to increased dysphagia.

Diabetes mellitus and the stomach.

Many patients with diabetes mellitus complain of early satiety and postprandial gastric fullness. In 1945, these symptoms were first found to result from a gastric motor dysfunction which makes the delivery of ingesta into the small intestine, the time of their absorption and the related blood-glucose rise unpredictable. Consequently, insulin or hypoglycaemic agents are administered at inappropriate time points and poor glycaemic control ensues. About 50% of patients with Type I (insulin-dependent) and Type II (non-insulin-dependent) diabetes mellitus are affected. Hyperglycaemia may play an important role in the disorder: gastric emptying was found to be slower in states of induced hyperglycaemia than in euglycaemia. However, significantly reduced blood-glucose concentrations after therapy readjustment were not associated with an increase in emptying rate. Prolonged hyperglycaemia could alter nerve metabolism and contribute to the development of neuropathy. Severity of cardiovascular autonomic neuropathy, but not actual blood-glucose and glycated haemoglobin level, has been found to correlate with the degree of emptying impairment. Drugs enhancing gastric emptying could improve the coordination between insulin administration and the onset of nutrient absorption and thus glycaemic control. Disappointingly, trials to study the long-term effects of such drugs are scarce and their results predominantly negative. In conclusion, many diabetic patients have impaired gastric motor function which could contribute to poor glycaemic control. Evidence suggests that autonomic neuropathy is the main underlying factor. This review aims to offer a critical survey of all the data available at present on these topics.

[Functional dyspepsia: philosopher's stone or much noise about nothing?]. / Funktionelle Dyspepsie: Stein der Weisen oder viel Lärm um nichts?

Does it make sense to diagnose functional dyspepsia? In 1998, a committee gathered in Rome recommended to diagnose functional dyspepsia in patients with persistent or recurrent pain or discomfort centered in the upper abdomen but no disease likely to explain the symptoms, which are not exclusively relieved by defecation or associated with changed stool frequency or form. Careful history taking, physical examination and upper endoscopy during a symptomatic period off anti-secretory therapy are recommended as minimum workup. Functional dyspepsia thus is a diagnosis of exclusion. The term is unfortunate: It suggests the presence of a manifest or yet covert organ dysfunction and also a fundamental difference between disorders with defined and with unknown cause, only the former being serious. However, that a limited number of investigations failed to reveal a cause does not mean that there is no cause. Further, functional often is used synonymous with vague and ideology-ridden terms such as "organ neurosis", "vegetative dystonia" and "psychosomatic disorder". There are no unequivocal data showing that patients with functional dyspepsia share pathophysiological, psychosocial or psychopathological characteristics or that there is a specific therapy. In the individual patient, therapy has to be tailored according to the symptoms. It thus seems doubtful whether the diagnosis functional dyspepsia can, for a patient's treatment or otherwise, be of value. If a categorization is deemed inevitable, the term idiopathic dyspepsia would be preferable, as it unequivocally makes clear that the symptoms' cause is unrevealed.

Cilansetron. Solvay.

Cilansetron is a 5-HT3 antagonist tinder development by Solvay Pharmaceuticals as a potential treatment for irritable bowel syndrome (IBS). The compound targets non-constipated men and women with IBS. Cilansetron is being evaluated in phase III trials, but up to now, only scarce information has been made available and most publications have appeared in abstract form only. In July 2001, it was reported that regulatory submissions were expected in 2003 [416185]. Also in July 2001, after discussion with the FDA, Solvay initiated a revised phase III program in diarrhea-predominant IBS and signed a five-year 'preferred-provider' clinical services agreement with Quintiles Transnational to conduct the trial. At this time, Solvay was also seeking marketing partners for cilansetron [416185]. By October 1999, Solvay was treating cilansetron as one of its main priorities, as it represented a novel class of compound [342434]. Solvay has predicted peak sales of euro 100 m to euro 1000 m [420654].

Epigastric fullness.

Epigastric fullness may be caused by a disordered gastric motor function, resulting in delayed gastric emptying, but may also be caused by rapid emptying, leading to a distention of the proximal small intestine. A rational diagnostic approach to a patient complaining of epigastric fullness is needed to reveal the underlying disorder or disease and to enable an adequate, targeted therapy. The clinical impression based on symptoms is unreliable and cannot distinguish function disorders and benign disease from severe conditions.

Gastric emptying: a contributory factor in gastro-oesophageal reflux activity?

AIMS: To evaluate the impact of total and proximal stomach emptying on 24 hour and postprandial reflux as well as the number of reflux episodes per hour in relation to the impact of lower oesophageal sphincter (LOS) pressure, and oesophageal contractile and clearance function. METHODS: Seventy one outpatients (37 female, 34 male; age 23-82 years) with symptoms suggestive of both delayed gastric emptying and reflux referred for further investigations participated in the study. Gastric emptying of a semisolid 1168 kJ meal and oesophageal clearance of a water bolus (supine) were recorded scintigraphically, reflux by 24 hour pH monitoring, and oesophageal motility manometrically. RESULTS: Slow proximal but not slow distal or total stomach emptying correlated with increased 24 hour and postprandial acid exposure and increased number of reflux episodes/hour. No relationship was found between total or proximal emptying and LOS resting pressure, oesophageal contraction amplitude, percentage of failed contractions, or clearance. Multiple linear regression analyses showed that slow proximal emptying and low LOS pressure contributed significantly to both 24 hour (p=0.0007 and p=0. 0001) and two hour postprandial acid exposure (p=0.007 and p=0.0001). In contrast, the rate of total emptying contributed to neither 24 hour nor postprandial acid exposure. CONCLUSION: Our data suggest that in contrast with total stomach emptying, the rate of proximal stomach emptying contributes to the extent of 24 hour as well as postprandial acid exposure and the number of reflux episodes/hour.

Effects of the 5-HT3 antagonist cilansetron vs placebo on phasic sigmoid colonic motility in healthy man: a double-blind crossover trial.

AIMS: 5-hydroxytryptamine3 receptor antagonists act antiemetically and slow colonic transit. This study evaluated effects of the high-affinity 5-HT3 antagonist, cilansetron, on fasting, meal-and anticholinesterase-stimulated phasic contractile activity of the human sigmoid colon as well as on bowel habits and stool consistency. METHODS: Five female and seven male healthy volunteers received, during three 7 day periods separated by 7 day wash-out periods, 4 mg cilansetron, 8 mg cilansetron or placebo three times daily orally under random, double-blind, crossover conditions. On day 8 of each treatment period, motility 20-40 cm from the anal verge was recorded using five pressure sensors spaced at 5 cm intervals. After a basal 30 min, subjects swallowed a further dose of the scheduled treatment; 60 min later, blood was taken for the determination of plasma cilansetron levels. Thereafter, subjects ingested a 4200 kJ meal and 250 ml sweetened mallow tea (166 kJ); 90 min after meal onset, 1 mg neostigmine was administered intramuscularly and motility recording was continued for 60 min RESULTS: Phasic contractile activity and intraluminal base-line pressure increased postprandially and more so after neostigmine. With cilansetron, the area under the pressure curve as the primary outcome variable and the number of contractions were significantly greater than with placebo (P = 0.005), amplitude and duration of contractions and base-line pressure were not affected. The effects of the two cilansetron dosages did not differ. With cilansetron, stool tended to become firmer. No adverse effects were observed. Plasma levels were highest with 8 mg cilansetron. CONCLUSIONS: Cilansetron slightly augments meal-stimulated and markedly neostigmine-stimulated phasic motility of the sigmoid colon. When administered over 7 days, it tends to increase stool consistency and is well tolerated.

Cardiovascular autonomic function, autoantibodies, and esophageal motor activity in patients with systemic sclerosis and mixed connective tissue disease.

OBJECTIVE: To study cardiovascular autonomic nerve function and presence of autoantibodies in relation to esophageal motor activity in patients with systemic sclerosis (SSc) and mixed connective tissue disease (MCTD). METHODS: Twenty-five patients with SSc (13 limited, 12 diffuse cutaneous disease; disease duration 1-19 yrs) and 6 patients with MCTD (disease duration 1-10 yrs) were studied. Cardiovascular autonomic function was assessed using 5 standard tests and autoantibody status determined. Esophageal motor activity and lower and upper esophageal sphincter pressures were recorded manometrically. RESULTS: Five patients with SSc had definite, 7 borderline, and 13 no autonomic dysfunction; 23 had antinuclear. 9 anti-Sc170, 4 anticentromere, and 1 U1snRNP antibodies. Contraction amplitudes in the smooth muscle as well as the striated muscle esophagus and lower esophageal sphincter pressures were significantly lower and autonomic dysfunction more frequent in patients with than in those without anti-Sc170 (6 of 9 vs 6 of 16 patients); upper esophageal sphincter pressures did not differ. All patients with MCTD had antinuclear antibodies, 5 had definite autonomic dysfunction; their lower esophageal sphincter pressures were significantly lower than in SSc patients without anti-Sc170 and anti-U1snRNP. CONCLUSION: Esophageal motor dysfunction may be associated with the presence of anti-Sc170 and anti-U1snRNP autoantibodies and prevail in patients with cardiovascular autonomic neuropathy.

Cisapride versus placebo for 8 weeks on glycemic control and gastric emptying in insulin-dependent diabetes: a double blind cross-over trial.

In insulin-dependent diabetes mellitus, slow gastric emptying may make absorption unpredictable and foster glycemic instability. Cisapride accelerates emptying, but controlled long term studies are scarce, and effects on glycemic control unknown. We investigated, in patients with insulin-dependent diabetes mellitus and unstable glycemia, the effects of 10 mg cisapride 4 times daily for 8 weeks vs. placebo on glycemic control and gastric emptying under random, cross-over, double blind conditions. In 14 patients with delayed and 9 with nondelayed emptying, blood glucose variability over 28-week treatment periods separated by a 4-week wash-out and gastric emptying of a semisolid 1168-kJ meal immediately after the treatment periods were assessed. Cisapride did not affect glycemic control [SD of within-patient mean blood glucose, 4.2 mmol/L +/-0.1 (+/- SEM) vs. 4.0+/-0.1 mmol/L after placebo; hemoglobin A1c, 8.3+/-0.2% vs. 8.5+/-0.2%]. Emptying was faster after cisapride than after placebo in 8 of 14 patients with delayed vs. 7 of 9 with nondelayed emptying (P = NS) and in 11 of 15 without vs. 4 of 8 with cardiovascular autonomic neuropathy (P = NS). Autonomic neuropathy prevailed in 7 of 14 patients with delayed and 1 of 9 with nondelayed emptying. Blood glucose immediately before and during assessment of emptying was unrelated to the emptying rate, whereas blood glucose increases over fasting levels were greater with faster emptying (P<0.002). In conclusion, cisapride's effects were not different from those of placebo on glycemic control and gastric emptying, it did not differently affect patients with delayed vs. nondelayed emptying, and it slightly accelerated emptying (P = NS) in patients without, but not in those with, cardiovascular autonomic neuropathy. Blood glucose levels before and during assessment of emptying did not affect emptying, but the glucose rise over fasting levels was greater with faster emptying.

Gastric emptying in Type II (non-insulin-dependent) diabetes mellitus before and after therapy readjustment: no influence of actual blood glucose concentration.

AIMS/HYPOTHESIS: Hyperglycaemia that is induced short-term slows gastric emptying in healthy subjects and patients with diabetes mellitus. Little information is available on the impact of longer-lasting, naturally occurring blood glucose increases and their reduction to euglycaemic values. We studied the relation between gastric emptying and pre-prandial and postprandial blood glucose concentrations in patients with Type II (non-insulin-dependent) diabetes mellitus and secondary failure to respond to oral hypoglycaemic treatment (a) before readjusting hypoglycaemic therapy and (b) 1 week thereafter. METHODS: We studied 9 female and 1 male patient (age 60-78 years, BMI 21.9-32.5 kg/m2, diabetes duration 3-33 years, HbA1c 8.8-13.2%). Gastric emptying of a radiolabelled semisolid 1168 kJ meal was recorded scintigraphically. RESULTS: Blood glucose concentration pre-prandial and postprandial was considerably lower subsequent to than before therapy readjustment in all patients (fasting, 7.9 mmol/l+/-1.5 SD vs 11.7+/-1.7 mmol/l; 60 min postprandial, 11.7+/-2.0 vs 15.4+/-2.2 mmol/l). By contrast, gastric emptying was unchanged (residual radioactivity in stomach 50 min postprandial 65.7+/-14.1% vs 66.5+/-12.9%). There was no relation between emptying and either fasting blood glucose concentration or its postprandial increase. CONCLUSION/INTERPRETATION: The data do not support a major impact of actual, longer-lasting, naturally occurring blood glucose concentrations upon the rate of gastric emptying in patients with Type II diabetes.

Radiographic detection of achalasia: diagnostic accuracy of videofluoroscopy.

AIMS: To retrospectively evaluate the accuracy of videofluoroscopy in the diagnosis of achalasia. MATERIALS AND METHODS: Videofluoroscopic studies of the oesophagus of 53 patients (25 males, 28 females; mean age, 49 years) with manometrically revealed diagnosis of achalasia were retrospectively evaluated. The videofluoroscopic examinations had been carried out with one swallow of low-density barium suspension in the erect and up to three swallows in the prone oblique position. Videofluoroscopically, a diagnosis of achalasia was made in 31 of the patients (58%) with manometrically proven achalasia, of whom only nine had oesophageal dilatation. Non-specific oesophageal motor abnormalities were diagnosed radiographically in 18 patients (34%) and a normal motility in four patients (8%). CONCLUSION: Videofluoroscopy is a valuable and sensitive technique for the detection of disordered oesophageal motility in achalasia.

Globus sensation: pharyngoesophageal function, psychometric and psychiatric findings, and follow-up in 88 patients.

BACKGROUND: The globus sensation has been widely regarded as psychogenic, but organic disorders were found to be etiologically significant. OBJECTIVE: To investigate the structural, functional, psychological, and psychiatric factors possibly eliciting the globus sensation and influencing its course. METHODS: Eighty-eight patients, 67 women and 21 men (aged 22-71 years), referred to 2 tertiary care centers underwent history taking, otolaryngological examination, pharyngoesophageal videofluoroscopy and manometry, psychosocial evaluation, psychometric tests, psychiatric interview, and when indicated, esophagogastroduodenoscopy, esophageal bolus transport, gastroesophageal reflux, and gastric emptying studies. According to revealed disorders, therapy was initiated, and the outcome was studied. RESULTS: Only 15 patients had normal pharyngoesophageal function; of these 15, 6 had chronic tonsillitis or pharyngitis, 3 had thyroid adenomata, 4 had cervical spondylosis, and 1 each had dry oropharyngeal mucosa and chronic bronchitis. Of the other 73 patients, 2 had pharyngeal dysfunction, 24 had achalasia, 1 had diffuse esophageal spasms, 3 had "nutcracker esophagus," 30 had nonspecific esophageal motor disorders, and 13 had gastroesophageal reflux. Psychometry revealed no more anxiety and depression than in general medical outpatients. Of 58 patients interviewed, 37 met criteria for psychiatric disorders. Psychometric scores and psychiatric characteristics were unrelated to the sensation's course. Therapy was recommended, but only 26 patients were treated accordingly; 22 received nonspecific treatment. Follow-up 3 to 59 months later revealed that the sensation had vanished in 13 patients who had received specific treatment, 5 who had received nonspecific treatment, and 6 who had received no treatment; it was alleviated in 10 who had received specific treatment, 13 who had received nonspecific treatment, and 9 who had received no treatment; and it was unchanged in 3 who had received specific treatment, 5 who had received nonspecific treatment, and 23 patients who had received no treatment. CONCLUSIONS: Pharyngoesophageal disorders may be sensed only vaguely, inducing the globus sensation. Psychological and psychiatric characteristics could be relevant to the discomfort experienced but are unlikely to be etiologically significant.

Effects of 3-days' intake of a sustained-release preparation of the nitric oxide donor, isosorbide dinitrate, on oesophageal motility.

BACKGROUND: Nitric oxide plays an important role in gastrointestinal motility. We evaluated the effects of a sustained-release preparation of the nitric oxide donor isosorbide dinitrate on swallow-initiated oesophageal contractions and the lower oesophageal sphincter. METHODS: Twelve healthy men, aged 23-32 years, received, at 1-week intervals and under random double-blind conditions, for 3 days either 20 mg isosorbide dinitrate, 40 mg isosorbide dinitrate or placebo twice daily (b.d.). One hour after a further dose on day 4, oesophageal motility was recorded for 30 min using a multilumen catheter with a Dent sleeve straddling the lower oesophageal sphincter and side-hole openings 0, 3, 6 and 9 cm proximal to the sleeve. Contractile responses to twelve 5-mL water swallows were evaluated. RESULTS: Amplitude, duration, propagation velocity and onset latency of oesophageal contractions were not affected by either dosage of isosorbide dinitrate. Lower oesophageal sphincter resting pressure was significantly lower after 40 mg (15.1 mmHg +/- 1.2 S.E.M.) and 20 mg isosorbide dinitrate b.d. (15.0 +/- 1.0 mmHg) than after placebo (17.9 +/- 1.7 mmHg; P < 0.025). Headache was reported by all subjects on 40 mg isosorbide dinitrate, seven subjects on 20 mg and by one on placebo. CONCLUSIONS: Twenty and 40 mg sustained-release isosorbide dinitrate twice daily had no effect on swallow-initiated oesophageal contractions but decreased lower oesophageal sphincter resting pressure.