The effect of trospium chloride on oesophageal motility.

Trospium chloride is a muscarinergic antagonist acting on oesophageal smooth muscle and on ganglionic and/or myenteric neurons. The effect of this drug on oesophageal motility was tested in 16 healthy male subjects in a double-blind randomized cross-over examination of trospium chloride or placebo following phentolamine or placebo application. Each subject underwent two separate investigations at least one week apart. Trospium chloride was effective in the oesophagus to reduce contractile activity (amplitude and duration of peristalsis) in all parts of the oesophageal body, and this effect was not blocked by phentolamine. Its potent action and its minor side-effects appear to be promising for clinical use in patients with motility disorders such as the hypercontractile oesophagus.

The effect of cisapride on defaecation in normal human subjects--lack of effect on faecal excretion of water, fat, and bile acids.

In order to elucidate whether or not the increased stool frequency that occurs during cisapride treatment is a result of malabsorption of water, fat, and bile acids, 12 healthy volunteers were dosed with either tablets of placebo q.d.s. or tablets of 10 mg cisapride q.d.s. during two periods of 5 days in a double-blind, crossover study. Stool frequency, stool consistency, and side-effects were recorded each day. Total faecal mass, faecal water content, and faecal excretion of fat and bile acids were determined during the last 72 h of each study period. Mean daily stool frequency was 18.8% higher during cisapride [1.68 +/- 0.12 (S.E.M.)] administration than during placebo (1.42 +/- 0.12); P = 0.038. The stool consistency score increased by 11.8% towards softer stools during cisapride dosing (N.S.). There were no significant differences in total faecal mass (placebo 399.4 g/72 h; cisapride; 414.5 g/72 h), faecal water content (placebo; 75.6%: cisapride 76.2%), or faecal excretion of fat (placebo; 12.7 g/72 h: cisapride; 11.6 g/72 h) and total bile acids (placebo; 2212 mumol/72 h: cisapride; 2261 mumol/72 h). The side-effects reported during placebo were constipation (n = 3), and during cisapride meteorism (n = 4) and increased appetite (n = 2). The increased stool frequency during cisapride treatment is not caused by malabsorption of water, fat, or bile acids, but seems to be the consequence of a direct motor effect.

Dose finding study of mosapride in functional dyspepsia: a placebo-controlled, randomized study.

BACKGROUND: Prokinetic agents have shown variable efficacy in the treatment of functional dyspepsia. Mosapride is a new prokinetic 5-hydroxytryptamine-4 agonistic agent. AIM: To evaluate the efficacy of three dosage regimens of mosapride compared with placebo in the treatment of functional dyspepsia. METHODS: Patients were randomly allocated to treatment with placebo or mosapride (5 mg b.d., 10 mg b.d. or 7.5 mg t.d.s.) in a double-blind, prospective, multicentre, multinational study. The change in symptom severity score from an untreated baseline week to the sixth week of treatment was used to compare treatment efficacy. RESULTS: There were 141, 140, 143 and 142 patients valid for evaluation in the intention-to-treat population in the placebo, mosapride 5 mg b.d., mosapride 10 mg b.d. and mosapride 7.5 mg t.d.s. groups, respectively. The mean changes in the overall dyspeptic symptom score were - 0.90, - 0.94, - 0.88 and - 0.89, respectively, and the proportions of patients feeling better at the end of the treatment period were 60%, 59%, 59% and 61%, respectively. No statistically significant difference was seen. CONCLUSIONS: Treatment of functional dyspepsia with mosapride was not superior to placebo. The result raises the question of whether treatment with prokinetic agents is appropriate for functional dyspepsia.

Effects of nutrient solutions on concentration analysis of non-absorbable dilution markers--implications for studies of gastric emptying.

Gastrointestinal luminal contents may interfere with concentration analysis of non-absorbable dyes. However, non-absorbable markers are broadly used for studies of gastric emptying rates of nutrient solutions. This prompted us to evaluate the properties of non-absorbable markers to mark such nutrient solutions. In vitro concentrations of polyethylene glycol, phenol red, dextran blue, two anthroquinone dyes and inulin were determined spectrophotometrically in the presence or absence of a formula diet, single compounds of the diet or an oligo-peptide diet, and the reproducibility and validity of the analyses were evaluated. The presence of the formula diet or the oligopeptide diet seriously impaired the analyses of marker concentrations, whereas single nutrient compounds did not uniformly interfere. The analysis of polyethylene glycol and phenol red concentrations was impaired by proteins, while the analysis of inulin concentration was impaired by carbohydrates. Dextran blue and the anthroquinones were completely eliminated by protein-precipitation procedures. In conclusion, phenol red and polyethylene glycol should only be used as marker substances for protein-free meals or nutrient solutions, while inulin should not be used with meals or nutrient solutions containing carbohydrates. Marker dilution techniques cannot be recommended for measurements of gastric emptying rates of complete meals.

Repeated noninvasive measurement of gastrointestinal transit in rats.

A technique for repeated and noninvasive measurement of oro-cecal transit time in rats and other small animals is described. It is based on the incomplete digestion of carbohydrates such as lactose fed orally to the animals. Since the activity of the enzyme lactase is low in almost all species, lactose is fermented by colonic bacteria after it arrived in the cecum, thus producing hydrogen. Hydrogen is delivered to the lungs via the circulation and exhaled by the animal. An increase in breath hydrogen measured by means of an electrochemical cell or a gas-chromatograph indicates the arrival of the nutrient bolus in the cecum. The method can be used repeatedly in individual animals under various experimental conditions such as investigations of stress effects on gastrointestinal transit.

Postprandial gastric relaxation in achalasia.

BACKGROUND: In achalasia the incidence of autonomic neuropathy is increased, indicating that achalasia is not a disease of the oesophagus only. Little information is available concerning the function of the stomach in achalasia. We compared the postprandial gastric fundus relaxation in patients with achalasia to that of healthy controls. METHODS: In six patients with achalasia and six healthy controls postprandial fundus relaxation after a liquid test meal (500 ml, 500 kcal) was studied using an intragastric bag connected to an electronic barostat. The postprandial gastric relaxation was measured as an increase of intragastric bag volume; bag pressure was set at a constant level of 1 mmHg above the intra-abdominal pressure. All data are given as means +/- SEM, and the Mann-Whitney test was used for statistical analysis. RESULTS: The intragastric volume before ingestion of the test meal was not different between groups. The maximum relaxation in patients with achalasia was significantly lower than in controls (132+/-46 ml vs 238+/-70 ml, P< 0.02). Postprandial relaxation was diminished and shortened in patients with achalasia as compared with controls. Similarly, the area under the volume curve was significantly smaller in patients with achalasia than in controls (29.8+/-28.9 ml/h vs 102.9+/-58.4 ml/h, P< 0.03) consistent with a diminished postprandial relaxation. CONCLUSION: Patients with achalasia show a decreased postprandial gastric relaxation compared with healthy controls. We hypothesize that the neural damage in achalasia is not restricted to the oesophagus, but also involves the proximal stomach.

Gastric emptying in liver cirrhosis. The effect of the type of meal.

OBJECTIVE: Contradictory reports have been published on gastric emptying in patients with liver cirrhosis. The differences have been attributed to differences in the innervation of the stomach or in the behaviour of the gastric wall. The type of test meal used may, however, have its importance. We looked for the role of the test meal in the assessment of gastric emptying in cirrhosis. DESIGN: In a prospective study, we included 15 patients with liver cirrhosis who had no symptoms of autonomic neuropathy, portal hypertensive gastropathy or antral vascular ectasia and 15 controls. In these subjects we estimated the gastric emptying and varied the type of test meals. METHODS: An ultrasonographic method was used for the estimation of gastric emptying. Antral area was monitored in the aorto-mesenteric plane in the fasting condition and at 0, 15, 30, 45, 60 min after a test meal. Each patient was tested twice on 2 consecutive days in randomized order with a liquid meal (220 kJ) and a semisolid meal (1472 kJ). RESULTS: Fasting antral areas (mean +/- SD) had similar size in both groups with both meals. Gastric emptying (expressed by the area under the curve and half-time (T1/2)) of the semisolid meal was not different in cirrhosis (2347 +/- 1648) compared to controls (2840 +/- 1983). Postprandial antral distension was also similar in both groups (312.2 +/- 133.6% in cirrhosis vs. 397.9 +/- 155.6% in controls). But emptying of the liquid meal was accelerated in the cirrhotic patients with respect to the area under the curve (AUC: 882 +/- 548) and half-time (12 +/- 2 min) vs. controls (AUC: 1863 +/- 1088, P<0.01; T1/2: 18 +/- 7 min, P<0.05). Postprandial antral distension with the liquid meal was decreased (299.4 +/- 76.5% vs. 431.5 +/-154.0%, P<0.01, in controls). CONCLUSION: These data suggest that in patients with liver cirrhosis free of autonomic neuropathy and without portal hypertensive gastropathy or vascular antral ectasia, gastric emptying of liquid low calorie meals is accelerated. The gastric emptying of a semisolid meal richer in calories is normal. Thus, the physical and chemical properties of a meal are major determinants of gastric emptying and may account for the large divergence of results hitherto published on this topic.

24-hour oesophageal motility in gastro-oesophageal reflux disease (GORD): increased occurrence of simultaneous contractions.

Impaired oesophageal peristalsis may play a major pathogenetic role in gastro-oesophageal reflux disease (GORD). Therefore 55 patients with suspected GORD were studied simultaneously by ambulatory 24-hour pH and pressure monitoring with three pressure transducers (3, 8 and 13 cm above the lower oesophageal sphincter) in order to to test for a relationship between oesophageal motility and GOR. Twenty-one patients (38%) had pathological reflux; these patients had significantly more simultaneous contractions than patients without pathological GOR (30.1 +/- 3.3% vs. 19.0 +/- 1.8%, P = 0.002, mean +/- SEM). Further analysis revealed a significant difference between groups in the occurrence of simultaneous contractions in the mid-oesophagus (33.7 +/- 3.8% vs. 23.9 +/- 1.8%, P = 0.012), but not in the distal oesophagus (34.4 +/- 2.7% vs. 33.9 +/- 3.1%, P = 0.90). In addition, a moderate but highly significant correlation between the rate of simultaneous contractions and reflux time was found (r = 0.463, P = 0.0005). Mean amplitude and mean duration of the contractions were no different between groups, neither in the proximal (43.4 +/- 3.3 mmHg vs. 44.9 +/- 1.9 mmHg, P = 0.68 and 2.4 +/- 0.2s vs. 2.5 +/- 0.1s, P = 0.50, respectively) nor in the distal oesophagus (48.8 +/- 4.6 mmHg vs. 54.2 +/- 3.4 mmHg, P = 0.34 and 3.0 +/- 0.2s vs. 2.9 +/- 0.2s, P = 0.71, respectively). It was concluded that pathological GOR is associated with an increased occurrence of simultaneous contractions in the mid, but not in the distal, oesophagus.

The effect of cisapride on dysmotility-like functional dyspepsia: reduction of the fasting and postprandial area, but not of the postprandial antral expansion.

OBJECTIVE: To test the effect of cisapride on symptom score and on fasting and postprandial antral area in patients with dysmotility-like functional dyspepsia compared with controls. METHODS: Nineteen consecutive patients with dysmotility-like functional dyspepsia (13 females, six males, aged 18-79 y) and 12 control subjects (six females, six males, aged 19-68 y) were investigated. A symptom score including six upper digestive symptoms rated from 0 to 3 was applied. The patients received in a randomized order cisapride 10 mg t.i.d. (n = 10), or placebo (n = 9) for 3 days. The controls also received cisapride (n = 6) or placebo (n = 6) in the same way. The antral area in fasting condition and immediately after a semiliquid test meal (250 ml, 342 kcal) was assessed by real-time ultrasonography in front of the aorta and mesenteric vein. The measurements were carried out before starting and after finishing the trials with cisapride and placebo. RESULTS: The symptom score (mean +/- SD) was 7.1 +/- 2.4 in dysmotility-like functional dyspepsia vs 0.5 +/- 0.2 in controls (P < 0.0001). The fasting antral area was 4.5 +/- 0.9 cm2 in dysmotility-like functional dyspepsia vs 2.2 +/- 0.2 cm2 in controls (P < 0.0001). Postprandial antral area was also larger in dysmotility-like dyspepsia than in controls (6.2 +/- 1.0 vs 3.0 +/- 0.3 cm2, Pb= 0.0001). Symptom score correlated with fasting antral area in dysmotility-like functional dyspepsia (rb= 0.38, Pb= 0.05). Cisapride decreased the symptom score to 4.5 +/- 2.5 (P = 0.0009) and placebo to 5.3 +/- 2.4 (P = 0.02). Cisapride significantly reduced the fasting antral area and the postprandial antral area in the dyspeptic group, but not in the control group. Postprandial antral expansion was not influenced by cisapride. Placebo did not change the sonographic parameters in both groups. CONCLUSIONS: In dysmotility-like functional dyspepsia, fasting and postprandial antral areas are wider than in controls. Despite a good placebo response, cisapride is effective in improving the symptoms in dysmotility-like functional dyspepsia, associated with the reduction of fasting and postprandial antral areas.

Eradication of Helicobacter pylori in peptic ulcer disease with amoxycillin, 2.0 g, and omeprazole, 80 or 120 mg: a prospective randomized trial.

BACKGROUND: The appropriate dose of proton pump inhibitors needed for eradicating Helicobacter pylori by dual therapy is still controversial. DESIGN: The study was conducted as a single-blind, single-centre trial. METHODS: Fifty-four patients with active duodenal ulcers were treated with amoxycillin tablets, 750 mg three times daily, and omeprazole, either 40 mg twice daily (group 1) or 40 mg three times daily (group 2), for 14 days in a prospective randomized trial. H. pylori eradication was assessed 10 weeks after starting treatment. Biopsies were taken for rapid urease tests and histological analysis and 13C-urea breath tests were ordered. RESULTS: In both groups ulcer healing was complete in 96.3% of patients after 10 weeks. Ten weeks after starting treatment, Helicobacter pylori was eradicated in 76.9% of the patients in group 1 and 74.1% of those in group 2, as shown by rapid urease tests and histological analysis. In the subgroup of fully compliant patients (n = 49) the eradication rates were 80% and 79.2%, respectively. Hyperacidity significantly reduced the eradication rates. Patients showing successful H. pylori eradication were significantly older (59 +/- 14.0 years vs. 49 +/- 15.6 years; P = 0.025). Eradication rates were lower in smokers than in non-smokers (36.4% vs. 83.9%; P = 0.006). CONCLUSION: It is concluded that higher omeprazole doses should be reserved for younger patients and smokers; in others they are not needed.

Pneumatic dilation in achalasia.

Pneumatic dilation is the most common first-line therapy for the treatment of achalasia. The aim of dilation is a controlled disruption of circular muscle fibres of the lower esophageal sphincter to reduce the functional obstruction. Several types of dilators and different dilation techniques are used, but the achieved results are similar. The mean success rate is about 80% in the short term, but some patients need redilation in the further course (particularly young patients). Best long term results are obtained if the lower esophageal sphincter pressure can be reduced below 10 mmHg. Major complications are rare after pneumatic dilation; the most serious complication is esophageal perforation, which occurs at a mean rate of about 2.5%. Considering the pros and cons of other effective forms of treatment of achalasia (esophagomyotomy and intrasphincteric injection of botulinum toxin), pneumatic dilation is still the treatment of choice in the majority of patients with achalasia.

Autonomic nervous system evaluation: diagnosis of rectal and lower gut dysfunction.

The main symptoms of autonomic dysfunction of the lower gut are diarrhoea, constipation and faecal incontinence, but these symptoms are not specific. The main diagnostic procedures in the evaluation of the lower gut are transit studies with radiopaque markers, hydrogen breath tests, tests for the differentiation between osmotic and secretory diarrhoea (fasting test and/or stool analysis for electrolytes and osmolality), anorectal manometry and EMG of the anal sphincters.

A hitherto unknown pattern of pathologic gastrointestinal motility--a cause of repeated vomiting?

We report the case of a 20-year-old woman with functional vomiting who presented with symptoms of anorexia nervosa. Antroduodenal and upper jejunal perfusion manometry was performed using an eight-lumen catheter. The investigation revealed a hitherto unknown motility pattern consisting of continuous simultaneous contractions at high frequency from the antrum down to the upper jejunum. The observation suggests that this disorder was related to the patients symptomatology.

Breath hydrogen as a test for gastrointestinal transit.

Intestinal transit is an important indicator of small-bowel function. This study served to investigate oro-cecal and duodeno-cecal transit times of different carbohydrate test meals and to evaluate intra- and interindividual variability of the breath hydrogen test. Breath hydrogen was analysed by an electrochemical cell in 25 healthy volunteers. Oro-cecal transit time of lactulose was much shorter than that of a standardized normal test meal. Duodeno-cecal transit was approximately one hour shorter than oro-cecal transit. Considerable intra- and interindividual differences were observed. It is concluded that results of lactulose test meals do not permit conclusions as to the physiological situation. Large intra- and interindividual variability of transit times must be taken into account in any study using the breath hydrogen test.

[Surgical indications in cricopharyngeal dysfunction]. / Operationsindikation bei cricopharyngealer Dysfunktion.

In 1989, five patients were treated for a cricopharyngeal dysfunction by cervical myotomy. In the past, due to extremely limited indications for surgery, repeated efforts of conservative treatment had been attempted in patients with idiopathic cricopharyngeal dysfunction and tracheopulmonary aspiration and/or permanent inability of oral nourishment. These patients underwent surgery after an interdisciplinary clinical assessment. Four out of five patients showed immediate improvement of their serious symptoms. Cervical myotomy is not expected to be successful in patients with insufficient oropharyngeal propulsion, as we could see in one female patient with severe upper oesophageal sphincter spasm. According to the literature and to our results, approximately 70 to 90% of the patients with idiopathic dysfunction of the cricopharyngeal muscle, who underwent surgery, showed significant improvement or even recovery. Due to the multifactoral genesis of the cricopharyngeal dysfunction it is understandable, that the surgical result is heavily dependent on the preoperative interdisciplinary diagnosis. In summary, for idiopathic cricopharyngeal dysfunction with complications we recommend the early and technically simple operation.

[Bedside determination of clinical-chemical quantities using dry chemistry in an emergency admission]. / Patientennahe Bestimmung klinisch-chemischer Kenngrössen mittels Trockenchemie in einer Notaufnahme.

We evaluated the clinical relevance and reliability of a solid phase chemistry apparatus (Seralyzer) installed for near-patient testing of CK, GOT, glucose and potassium in the emergency admission of our hospital. Calibrations and quality controls were done by technologists of the central laboratory, the analyses were performed by the nursing staff after appropriate training. The rapid availability of the laboratory tests shortened the diagnostic process in only 8% of the patients. Clinical chemistry test results, therefore, appear to be of minor importance in making the diagnosis in an emergency room. The coefficients of variation of the inter-operator imprecision varied between 2.1 and 8.8% (means = 5.06%), when the measurements were performed by persons with no professional laboratory training, and between 2.7 and 8.5% (means = 3.98%) for skilled laboratory personal. In order to test the accuracy we correlated the dry chemistry values measured by the nurses in the daily routine with the results of a wet chemistry system. The Spearman rank correlation coefficients ranged between 0.916 and 0.950. Thus after appropriate training non-laboratory personal is able to perform dry chemistry testing with adequate precision and accuracy provided a competent supervision is guaranteed.

Evaluation of the Crohn's Disease Activity Index (CDAI) and the Dutch Index for severity and activity of Crohn's disease. An analysis of the data from the European Cooperative Crohn's Disease Study.

In the European Cooperative Crohn's Disease Study a general documentation of clinical and laboratory data was made at the entry into the study in 452 patients. These patients were in different states of their disease from quiescent to very active. In all patients the Crohn's Disease Activity Index of Best (CDAI) and the Dutch Index of van Hees was calculated. Three gastroenterologists did a global clinical rating and a separate laboratory rating without knowledge of the indices. The ratings were then correlated with the indices in the individual patients. The clinical rating correlated well with the CDAI (r = 0.88) and less with the Dutch Index (r = 0.672). On the other hand the laboratory rating showed a better correlation with the Dutch Index (r = 0.742) than with the CDAI (r = 0.573). This demonstrates that the CDAI preferably is an estimate of the clinical severity of the disease and not of the activity of inflammation. Vice versa the Dutch Index is mainly reflecting the activity of the inflammatory process.

[Therapeutic strategy in constipation]. / Therapeutische Strategie bei Obstipation.

Therapy of constipation is complex. It is mainly based on general rules and treatment with dietary fibres. If drugs are necessary they should be applied according to the type of constipation as evidenced by the results of special diagnostic procedures. Surgical treatment is only the last choice. The aim of therapy is to relieve the patient from his symptoms and achieve a habit of regular defecation, if possible without the application of laxatives. The foremost problem in the treatment of constipation is to interrupt the vicious circle 'constipation/abuse of laxatives.' Many patients only consult a physician when they are already in that problem. Therapy then becomes difficult. Information on bowel movements and on how to prevent constipation by the way of living, therefore, should be widely spread in the general population in order to minimize constipation as a medical problem.

Esophageal disorders in the etiology and pathophysiology of dyspepsia.

Dyspepsia may be caused by reflux esophagitis. We evaluated the symptoms of 45 patients aged 52 +/- 14 years who had a follow-up of 1 to 5 years. Endoscopy and histology demonstrated microscopic inflammation in 14, isolated mucosal defects in 12 and severe inflammation in 19 of the 45 patients. Belching was the leading symptom in patients with microscopic and severe esophagitis, heartburn in mild esophagitis. Upper abdominal pain, nausea and vomiting were present in 31%, 24% and 22% of the patients, respectively. Thus, reflux esophagitis is frequently accompanied by symptoms of dyspepsia which resemble those of other causes of dyspepsia. In contrast, disorders of gastric and intestinal motility may be associated with esophageal motor disturbances, particularly in gastric dysrhythmia, diabetic gastroenteropathy, irritable bowel syndrome, and idiopathic intestinal pseudo-obstruction. How much the esophagus contributes to the clinical symptomatology of dyspepsia awaits further elucidation.

Epidemiology of reflux disease and reflux esophagitis.

Symptomatic gastroesophageal reflux is a common medical problem. But only few data exist on the epidemiology of reflux disease (without inflammation) and reflux esophagitis. The literature is critically reviewed and ecological causes of gastroesophageal reflux are discussed. The prevalence of reflux esophagitis in Western countries is estimated to be 2% and that of reflux disease 5%. Sparse reports exist on the natural history of both diseases. They appear to have little if any effect on life expectancy. The main complications of reflux esophagitis are Barrett's esophagus, peptic stricture, ulceration and bleeding.