Randomised double-blind comparison of simethicone with cisapride in functional dyspepsia.

AIM: To compare the efficacy of simethicone with cisapride in patients with functional (non-ulcer) dyspepsia. METHODS: After standardized diagnostic work-up and at least 6-days wash-out of medication, 177 patients with functional dyspepsia were enrolled; 173 of them (age 19-71 years) were randomized and treated using a double-dummy technique with simethicone (84 mg t.d.s.) or cisapride (10 mg t.d.s.). At baseline and after 2 and 4 weeks, the intensity of the symptoms was scored from 0 (absent) to 3 (severe) using a standardized symptom questionnaire. Efficacy of the treatment was judged by the patients as 'very good', 'good', 'moderate' or 'no effect'. RESULTS: A total of 166 patients completed the trial. After 2 and 4 weeks, 34% and 46% (respectively), of the patients treated with simethicone judged the improvement in symptoms to be excellent compared to 13% and 22% (respectively) of patients treated with cisapride (P < 0.01). After 2 weeks the difference in the improvement in the global symptom score was significantly better (Delta30.7%, P < 0.001) for simethicone than for cisapride, while this difference failed statistical significance after 4 weeks (Delta10.2%, P=0.11). CONCLUSIONS: In patients with functional dyspepsia, simethicone relieves symptoms during the first 2 weeks of treatment significantly better than cisapride.

Effects of CCK-receptor antagonist on colonic motor activity in dogs.

This study employed a cholecystokinin (CCK) antagonist to evaluate whether endogenous CCK regulates fasted and fed motor patterns of the colon. Experiments were performed in six conscious dogs, each in duplicate. Motor activity was recorded by four strain gauge transducers implanted on the colon. The effects of the CCK-analogue caerulein and the CCK-antagonist loxiglumide (Rotta, Italy) were studied in fasted and fed states. The motor activity was computed for the area under contractions. Caerulein given as an intravenous bolus of 50 ng kg-1 during a quiescent state caused a burst of phasic and tonic contractions resembling a regular non-migrating motor complex. Physiological doses of 10 ng kg-1 caerulein, which increases plasma CCK-immunoreactivity to postprandial levels, had no effect. Continuous intravenous infusion of 10 mg kg-1 h-1 loxiglumide completely abolished the effects of 50 ng kg-1 caerulein. The motor activity stimulated by the cholinesterase inhibitor neostigmine (10 micrograms kg-1) was not altered by loxiglumide. Loxiglumide given in the fasted state reduced the area under contractions in the proximal colon by 26.8 +/- 12.8% compared to the control without loxiglumide (P < 0.05). The postprandial increase in motor activity in the distal colon, the gastrocolonic response, was significantly inhibited by loxiglumide. Moreover, loxiglumide reduced the area under contractions in the fed state by 25.4 +/- 10.7% and 19 +/- 7.2% in the proximal and distal colon, respectively (P < 0.05). The present results show that loxiglumide acts as a specific antagonist of the actions of CCK on colonic motor activity in the dog.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of absorption rate, flow rate and fluid load on colonic motor activity in dogs.

We investigated the relationship between absorption rate, flow rate, fluid load and colonic motor activity in an in vivo isolated colonic loop model. Motor activity was recorded by implanted strain gauge transducers. Two electrolyte solutions were perfused at 0.4 and 1.6 mL min-1 through the open colonic loop (distal end open) or infused into the closed loop (distal end closed). The first solution resembled ileostomy fluid (ES1) and the second solution was an iso-osmolar mannitol solution (ES2). The absorption rate for H2O measured by 14C PEG concentrations of ES2, 0.2 +/- 0.03 mL min-1, was significantly less than that of ES1, 0.6 +/- 0.06 mL min-1. Infusion of ES1 under open loop conditions served as control. Motor activity was analysed for area under contractions and expressed as motor index ratio in comparison to the control. None of the solutions altered motor activity when perfused at the two rates through the open loop. Under closed loop conditions, the infusion of either solution at 0.4 mL min-1 had no significant effect on colonic motor activity. Infusion of ES1 or ES2 at 1.6 mL min-1 into the closed loop, however, increased the motor index ratio 2.5-fold and 3.6-fold, respectively (P < 0.01). The proximal half of the colon was less affected than the distal half during infusion of ES1 but not during infusion of ES2. We conclude that flow rate and absorption rate do not influence colonic motor activity as long as the fluids can leave the colon. When the distal end is closed, inflow, resulting in fluid accumulation and distension, leads to stimulation of colonic motor activity.

Magnetic marker monitoring of disintegrating capsules.

Magnetic marker monitoring was studied for its applicability to investigate the in vivo fate and behavior of disintegrating magnetically marked dosage forms. As a model, hard gelatin capsules were filled with an effervescent mixture of lactose, ascorbic acid and sodium hydrogen carbonate containing 1.3 mg black iron oxide as a magnetic label. The accuracy of the localization procedure whilst calculating all parameters of the dipole in one fitting procedure was checked in phantom experiments where the capsules were moved in well-defined paths with respect to the measurement device. The calculated position coordinates of the capsules deviated between less than 2 mm up to 8 mm from the expected position values depending on the distance between the sensor area and the capsule's path. Further experiments on the in vitro disintegration of the capsules showed that the value of the magnetic moment of the capsules can serve as a measure for their disintegration behavior. In vivo monitoring of the capsules was performed in eight experiments where a healthy volunteer swallowed each time one of the capsules. It was found that the in vivo disintegration behavior of the capsules corresponds well to their disintegration observed in water of about 37 degrees C.

Magnetic marker monitoring of esophageal, gastric and duodenal transit of non-disintegrating capsules.

The purpose of the study was to investigate in detail the esophageal, gastric and duodenal passage of non-disintegrating capsules in a fasted, healthy volunteer using Magnetic Marker Monitoring (MMM). Five independent experiments were performed. In each case the same healthy male volunteer ingested one magnetically marked capsule after fasting for at least 8 h. The magnetic dipole fields of the capsules were recorded by biomagnetic multichannel measuring equipment. The positions of the capsules were calculated from the recorded data by methods established in magnetic source imaging. The esophageal, gastric and duodenal passages of the capsules were successfully reconstructed from all recorded data sets. The spatial resolution of the capsules' three-dimensional positions in the organs of the gastrointestinal tract was within a range of several millimeters, with a chosen temporal resolution of up to four milliseconds. The esophageal transit times were between 3-13 s, the gastric residence times were between 14-133 min and the duodenal transit times were between 7-245 s. The data demonstrate that Magnetic Marker Monitoring permits the detailed investigation of the gastrointestinal transit of solids.

CD4+ immune response as a potential biomarker of patient reported inflammatory bowel disease (IBD) activity.

BACKGROUND: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBDs) which are characterized by dysfunctional regulation of the immune system. A number of immune modifying drugs are used to treat CD and UC. Therapy is adjusted largely on the bases of subjective reports of disease activity and non-specific laboratory tests. Identification of a single or combination of immune markers of disease activity could be useful to select and monitor therapeutic responses. However, to date no reliable quantitative associations between IBD activity and laboratory measures of immune function have been identified. This study was designed to evaluate the usefulness of a commercially available laboratory measure of CD4(+) immune function, the Cylex® ImmuKnow®, as a surrogate marker of IBD activity. METHODS: Adult IBD patients with either CD (N=55, 27 males, mean, SD age=38.5, 11.5 years) or UC (N=45, 24 males, mean, SD age=41.7, 15.4 years) were enrolled. Patients both in clinical remission and with active disease provided responses to structured, validated questionnaires (CDAI and HBI for CD patients and SCCAI for UC patients) used to monitor IBD activity. Whole blood and plasma samples were collected to quantify various markers of disease status including routine cell counts and differentials (CBCs), CRP, and albumin (Alb), as well as CD4(+) immune response (Cylex® ImmuKnow®, N=98). Results were compared between all IBD patients as well as between CD and UC subgroups. RESULTS: There was a good correlation between the results of CDAI and HBI scores (r=0.811, p<0.01, Spearman-Rho) but HBI scores correlated slightly better (r=0.575, p<0.001) than the CDAI's (r=0.449, p=0.001) with CD patients' reported perception of their general condition. CDAI and HBI scores categorized 12/55 versus 36/55 of CD patients respectively as having active disease. SCCAI scores indicated that 25/45 of UC patients had active disease. Cylex® results (in ng/mL of ATP) were increased in 74/98 IBD subjects (≥525 ng/mL) but were influenced by the use of systemic corticosteroids (SCS) and infliximab. There were weak but statistically significant Spearman-Rho correlations between Alb concentrations and both CDAI (r=0.413, p=0.002) and HBI (r=0.325, p=0.017) scores as well as between CRP values and HBI scores (r=0.331, p=0.016). Correlations between CRP and both CDAI and SCCAI scores and between Alb and SCCAI scores were not significant and there were no significant positive associations between any of the three clinical scores and Cylex® results. CONCLUSIONS: CD4(+) immune responses were significantly elevated in IBD patients whether or not they were in clinical remission but were influenced by treatment. There were some significant correlations between the clinical scores and CRP or Alb but not with the CD4(+) results. Both other clinical scoring systems, other measures of immune function, and CD4(+) immune response changes over time should be examined to see if this or other laboratory measures of immune response are predictive of actual disease activity or symptoms in CD or UC patients.

[Anorectal manometry]. / Empfehlungen zur Anorektalen Manometrie im Erwachsenenalter.

This document contains the guidelines of the German Societies of Neurogastroenterology and Motility, Gastroenterology (committee for proctology), Abdominal Surgery (coloproctology working group), and Coloproctology for anorectal manometry in adults. Recommendations are given about technical notes, study preparation (equipment; patient), technique for performing manometry and data analysis, reproducibility, and indications. Minimum standards for anorectal manometry are measurement of resting and squeeze pressure, testing of rectoanal inhibitory reflex, determination of rectal sensation (first perception and urge), and calculation of rectal compliance. Anorectal manometry is indicated in patients with fecal incontinence and constipation in the context of a structured programme.

The effects of deoxycholic and ricinoleic acid on the isolated circular muscle of the cat colon are modified by leucine-enkephalin.

The mechanism of the diarrheogenic effect of bile acids and fatty acids is incompletely understood. In order to study their effects on motility we tested sodium deoxycholate and sodium ricinoleate in their actions on the spontaneous mechanical and myoelectrical activity of the isolated circular muscle of the cat colon in a perfusion apparatus. Sodium deoxycholate activated the muscle in concentrations from 10(-9) to 10(-5) M. ED50 was 6.3 X 10(-9) M, ED100 10(-6) M. Sodium ricinoleate similarly stimulated muscle contractions. ED50 was 2.3 X 10(-7) M, ED100 5.1 X 10(-6) M. Both agents increased the occurrence of oscillating potentials in the myoelectrical records. Oscillations probably correspond to the migrating electrical complexes in diarrhea. The addition of leucine-enkephalin augmented primarily the number of brief spike potentials which may correspond to segmenting contractions. Thus, bile acids and fatty acids cause profound changes in colonic motility which by themselves may promote diarrhea. The endogenous opiate leucine-enkephalin could possibly counteract these effects.

Effects of CCK receptor blockade on intestinal motor activity in conscious dogs.

This study employed a cholecystokinin (CCK) antagonist to evaluate whether endogenous CCK regulates fasted and fed motor patterns of the small intestine. Experiments were performed in six conscious dogs, each in duplicate. Motor activity was recorded by six strain-gauge transducers implanted along the small intestine. The effects of the CCK analogue caerulein and the CCK antagonist loxiglumide were studied in fasted and fed states. Computer analysis determined contractile frequency and area under contractions. Caerulein given as an intravenous bolus 30 min after phase III dose dependently caused a burst of phasic contractions preceded by a retrograde giant contraction. Continuous intravenous infusion of 10 mg.kg-1.h-1 loxiglumide completely abolished the effects of 10 ng/kg caerulein, which increases plasma CCK immunoreactivity to postprandial levels. Loxiglumide, at 10 mg.kg-1.h-1, markedly reduced the increase in phasic contractions due to a supraphysiological dose of 50 ng/kg caerulein to 14 +/- 6(SD)% of the control without loxiglumide (P less than 0.01). The motor activity stimulated by the cholinesterase inhibitor neostigmine (10 micrograms/kg) was not altered by loxiglumide. Loxiglumide given in the fasted state decreased contractile frequency from 9.5 +/- 0.7 to 8.1 +/- 0.6/min and reduced the area under contractions during phase II to 81 +/- 5% of the control without loxiglumide (P less than 0.05). Loxiglumide also decreased contractile frequency during the fed state from 9.7 +/- 0.6 to 8.3 +/- 0.5/min and reduced the area under contractions to 78 +/- 6% of the control without loxiglumide (P less than 0.05). Thus loxiglumide acts as a specific antagonist of the actions of CCK on small intestinal motor activity in the dog. Loxiglumide, at a dose that abolishes actions of endogenous CCK, significantly decreased fasting motor activity during phase II. Loxiglumide also significantly reduced motor responses to feeding but did not prevent interruption of migrating motor complex cycle by a meal. CCK plays a physiological role in regulation of fasting and fed motor activity of small intestine, although other factors in addition to CCK mediate meal-induced motor activity.

Colonic motility in humans--a growing understanding.

As yet, there is limited information about the relationship of colonic motility to colonic flow or transit. The overall flow in the colon is slow and highly variable. The measurement of total and segmental transit time is essential for the differentiation of motor disorders associated with delayed transit. Rapid movements of colonic contents (mass movements) occur only a few times during the day. Their motor equivalent is the giant contraction which migrates in the aborad direction at relatively high velocity. Motor activity in the colon is highly variable, with periods of contraction and motor quiescence. Contractions occur at different frequencies ranging from 2 to 13 cycles per minute. High frequency contractions are stationary. Their myoelectrical equivalent is short spike bursts. Long spike bursts result in sustained, low frequency contractions, which may migrate in both directions. Technological advances now make it possible to obtain ambulant manometric recordings from the colon for 24 h. Such studies show a circadian variation in colonic motility with increases of activity after meals and after awakening. Motor disorders of the colon are not associated with specific abnormal motor patterns. Rather, they are due to changes in the occurrence of motor patterns seen in health. In constipated patients with slow colonic transit the suppression of strong peristaltic activity is the most plausible common pathogenetic mechanism. In diarrhoeal states, propulsive activity such as the giant migrating contractions may be a major mechanism which promotes the passage of stools. There is no agreement that there is disordered basal colonic motor activity in IBS. There is, however, increasing evidence that in IBS the colon responds abnormally to eating, certain forms of stress and distension, and that this may relate to symptoms. The psychopathology of IBS patients is apparently the most important factor in the health care-seeking behaviour of the patients. No specific therapy has yet been shown to be convincingly effective.

[Motility of the large intestine]. / Dickdarmmotilität.

Colonic motility has a number of tasks to fulfill: mixing, storage and slow transportation of intestinal contents, and rapid evacuation of feces. All this requires complex motor patterns. Phases of contraction alternate with phases of motor inactivity. Contractile activity is controlled by the myoelectric activity. Spikes and oscillations are superimposed on the electrical control activity. Short spike bursts are associated with contractions of short duration and serve for mixing; long spike bursts and oscillations are accompanied by tonic contractions of long duration, and are mainly propulsive. Giant migrating contractions occur sporadically and result in the emptying of large sections of the colon. Disturbances of colonic motility are of pathogenetic significance in a number of diseases. This has diagnostic and therapeutic consequences.

[Pharyngitis, massive ESR elevation and hyperthyroidism in a 71-year-old female patient]. / Pharyngitis, Sturzsenkung und Hyperthyreose bei einer 71-jährigen Patientin.

We present a 71-year-old female patient suffering from a sore throat with unilateral neck swelling, pain on swallowing, subfebrile temperatures and general fatigue persisting for several weeks without any clinical signs of hyperthyroidism, although laboratory findings show high concentrations of T(3) and T(4) and a low TSH. A massive ESR elevation is found as well. Ultrasound reveals an inhomogeneous pattern of the thyroid gland with low echogenicity. (99m)Tc pertechnetate uptake is suppressed. The diagnosis of acute/subacute thyroiditis de Quervain is concluded. Therapeutic application of prednisone leads to a swift improvement, yet two weeks later asymptomatic hypothyroidism is diagnosed, requiring substitution of thyroxine. We discuss de Quervain's thyroiditis and the differential diagnosis of inflammatory disorders of the thyroid gland.

[Neural regulation of the secretion of the small and large intestines]. / Nervale Regulation der Dünndarm- und Dickdarmsekretion.

The small bowel and the colon are supplied by a dense network of nerves. Nervous control of secretion is influenced by peripheral and central nerves. The small and large intestine are tonically inhibited by the enteric nervous system, in particular by the submucous plexus, to maximally absorb fluid and electrolytes. Choleratoxin induced intestinal secretion may be suppressed by central opiate receptors, and central gamma-aminobutyric acid receptors may inhibit intestinal absorption. Besides the classical neurotransmitters acetylcholine and noradrenalin, which stimulate and inhibit, respectively, secretion, a large number of regulatory peptides and other substances which mainly act as cotransmitters and neuromodulators affect mucosal transport in the small and large intestine. Secretion induced by nerves appears to play a major role in diabetic and infectious diarrhea. The nervous control of secretion in the small and large intestine is an interesting area of current research in intestinal transport. So far already, the results shed new light in a better understanding of intestinal pathophysiology, and they point towards new therapeutic modalities in diarrhea and constipation.

Giant migrating contractions during defecation in the dog colon.

The colonic motor correlates of defecation were studied in 5 conscious dogs. A set of six strain-gauge transducers were implanted on the colon of each dog. An implanted cannula gave access to the terminal ileum. During a total control recording period of 230 h we observed 12 large-amplitude contractions that occurred spontaneously in the proximal colon and migrated caudad. We called them giant migrating contractions. The mean amplitude of these contractions was 2.8 times larger than the mean peak amplitude of phasic contractions during colonic motor complexes. The following stimuli were applied to induce defecation: 2 mg/kg guanethidine (i.v.), 30 micrograms/kg neostigmine (i.v.), 1-4 ml/kg castor oil (p.o.), 200 ml of 25% glucose (into ileum), and rectal distention by a balloon (120 ml). In 85% of experiments with guanethidine, neostigmine, glucose, and castor oil, giant migrating contractions occurred before defecation. The giant migrating contractions migrated over the entire colon or a part of its length. The migration velocity varied from 0.2 to 3.2 cm/s (mean +/- SE, 0.82 +/- 0.1 cm/s). In 11% of the experiments, giant contractions occurred almost simultaneously at different recording sites at the time of defecation. In 4% of the experiments giant contractions occurred only at a single site. Balloon expulsion was only rarely accompanied by giant contractions in the colon, and then occurred only at a distal site and did not migrate. We conclude that the colon has spontaneous but infrequent large-amplitude caudad-migrating contractions. These contractions may be the motor equivalent of mass movements. Defecation is usually preceded by colonic giant migrating contractions. The giant migrating contractions may provide a major force for defecation and be partially responsible for the evacuation of the colon during defecation. However, evacuation of contents such as a balloon seems to be possible without giant migrating contractions.

Cholecystokinin's role in regulation of colonic motility in health and in irritable bowel syndrome.

Colonic motor activity and plasma concentrations of cholecystokinin (CCK) both increase after oral intake of a meal. Thus, CCK had been thought to mediate the postprandial increase in colonic motor activity, which is termed gastrocolonic response. The present study used the substance loxiglumide, which acts as a specific antagonist at the CCK-A receptor, to evaluate this hypothesis. In the first set of experiments, eight healthy subjects were studied four times on separate days. A multilumen catheter was endoscopically placed with its tip lying in the descending colon. Motor activity was recorded by a low-compliance perfusion manometry system at six locations 60-45 cm from the anus. Basal activity was recorded for at least 2 hours to achieve steady-state conditions. The order of the following four experiments was randomized: (a) intravenous infusion of the CCK analogue cerulein at increasing doses (7.5, 15, 30, and 60 ng/kg.h, each given for 30 minutes); (b) intravenous cerulein plus 5 mg/kg.h loxiglumide; (c) a 1000-kcal solid/liquid meal consisting of regular German food; and (d) a meal plus 5 mg/kg.h loxiglumide. In the second set of experiments, eight patients with irritable bowel syndrome were studied twice on two separate days, and two experiments were performed n randomized order: (a) a 1000-kcal solid/liquid meal consisting of regular German food; or (b) a meal plus 5 mg/kg.h loxiglumide. The motor index was calculated as the area under contractions by a computerized system. The 1000-kcal meal markedly increased colonic motor activity. This gastrocolonic response was significantly greater in patients with irritable bowel syndrome than in healthy volunteers. Cerulein stimulated motor activity only at pharmacological doses (30-60 ng/kg.h), which resulted in plasma CCK levels markedly exceeding postprandial values. Loxiglumide abolished the effects of cerulein even at pharmacological doses. However, loxiglumide did not inhibit the gastrocolonic response to a regular meal either in healthy volunteers or in patients with irritable bowel syndrome. Loxiglumide also failed to alter the interdigestive colonic motor activity. Therefore, effects mediated by the CCK-A receptor do not play a major physiological role in the regulation of the interdigestive and postprandial motility of the left colon.