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Recently, we developed a disposable acid exposure sensor whose in vitro response to acid below pH 4 is linearly determined by the duration of exposure and the degree of acidity. The aim of the present study was to compare the SR to simultaneous esophageal pH and duodenogastroesophageal reflux (DGER) monitoring (Bilitec) in patients investigated for presumed gastroesophageal reflux disease (GERD). Twenty-six patients (16 men, mean age 46 +/- 2 years) with symptoms suggestive of GERD underwent 24-hr ambulatory pH monitoring and SR monitoring at 5 cm proximal to the LES. DGER monitoring was performed in 21 patients. Exposure of the esophagus to acid and to DGER were analyzed. These data were compared to SR. A significant correlation was found between the exposure of the distal esophagus to acid and SR (R = 0.85; P < 0.0001). Similarly, the area below a cutoff pH 4 was significantly correlated to SR (r = 0.81; P < 0.0001). SR was not correlated to DGER (r = 0.16; NS). At a cutoff of 50, the sensitivity and specificity of SR to predict esophageal acid exposure > 5% of time were 91% and 93%, respectively conclusion, the response of the acid exposure sensor is strongly correlated with the results of simultaneous esophageal pH monitoring. The sensor seems able to reliably predict pathological esophageal acid exposure. These findings warrant larger studies of the clinical potential of the acid exposure sensor in the diagnosis and quantification of GERD.

Twenty-four normal subjects and 64 symptomatic patients with various degrees of reflux disease (24 with reflux symptoms without esophagitis and 21 with mild and 19 with severe esophagitis) underwent quantitative 24-hr intraesophageal pH monitoring. Various reflux parameters during supine, interprandial, and postprandial periods were examined by binary logistic regression and by CART analysis to determine the sensitivity and specificity to separate the various groups of subjects and patients. The distinction was excellent between asymptomatic controls and patients with severe erosive esophagitis (sensitivity and specificity both 100% by logistic regression and 95% and 88%, respectively, by CART), but discrimination was poor when asymptomatic controls were compared to symptomatic patients without esophagitis (71% and 79% by logistic regression and 75% and 92% by CART), which is the most important indication for pH recording in clinical practice. A 3-hr postprandial pH recording was inadequate to distinguish the various groups. The acidity of the reflux episodes during the night appeared to be a crucial factor in the development of severe erosive esophagitis. The duration of esophageal acid exposure was another important factor in the development of reflux lesions.

We have developed a breath test to measure solid gastric emptying using a standardized scrambled egg test meal (250 kcal) labeled with [14C]octanoic acid or [13C]octanoic acid. In vitro incubation studies showed that octanoic acid is a reliable marker of the solid phase. The breath test was validated in 36 subjects by simultaneous radioscintigraphic and breath test measurements. Nine healthy volunteers were studied after intravenous administration of 200 mg erythromycin and peroral administration of 30 mg propantheline, respectively. Erythromycin significantly enhanced gastric emptying, while propantheline significantly reduced gastric emptying rates. We conclude that the [*C]octanoic breath test is a promising and reliable test for measuring the gastric emptying rate of solids.

To investigate permeability alterations of the macroscopically normal jejunum in Crohn's disease, the permeation of two probes was measured during perfusion of an isolated jejunal segment. The data were compared with the results obtained by the standard per oral test in the same patients. Test probes were PEG-400 and [51Cr]EDTA. Ten normal individuals, 12 patients with Crohn's ileitis or ileocolitis, and seven patients with isolated Crohn's colitis all with normal jejunum on x-ray series were studied. Upon perfusion of the proximal small bowel, the 3-hr [51Cr]EDTA excretion was significantly increased in ileitis patients (P = 0.023) as compared to normals. The excretion exceeded the highest value of normals in eight of 12 ileitis patients. The excretion in Crohn's colitis patients was not significantly increased (P = 0.24) and abnormal excretion was found only in one of the Crohn's colitis patients. PEG-400 permeation during perfusion did not differentiate between the groups, but five of the seven patients with isolated Crohn's colitis had PEG-400 excretion exceeding the highest value in normals. Overall, 13 of the 19 patients had increased permeation of one of the two probes through jejunal mucosa during perfusion. These data suggest that the permeability is increased in the majority of patients even in segments that seem normal on x-ray.

This study examined the effects of changes in body position on different swallowing parameters derived from manofluorographic examinations. Quantitative data were obtained in a group of 12 young healthy volunteers. They were all tested in the upright position; six of them were also evaluated in the supine position, and the other six in the upside down position. In the different positions all volunteers were able to swallow a liquid bolus without aspiration or stasis. However, the dynamics of the swallow became different. Lying down resulted in a pharyngeal transit time comparable with the upright position. The tongue driving force was higher and the hypopharyngeal suction power weakened. In the upside down position, the pharyngeal transit time became longer and the tongue driving force was even more powerful. There was no apparent difference in the traditional manometric parameters; the amplitude, duration, and propagation velocity of the pharyngeal contraction on swallowing did not change obviously in the different body positions.

The effect of acarbose on hydrolysis of a pure starch meal was investigated in normal subjects and ileostomy patients by means of 13CO2 breath tests and blood glucose levels as parameters of absorption, and of H2 breath tests, serum acetate levels, and ileal loss of carbohydrate as parameters of malabsorption. Additional information on the effect of acarbose on alpha-amylase activity was obtained by in vitro experiments. Acarbose (200 and 400 mg) significantly delayed starch absorption. Serum acetate was found to be a less sensitive marker of malabsorption than breath H2 excretion. After intake of 50 g starch plus 400 mg acarbose, 23-71% of the starch load was lost in the ileostomy effluent, for a large part as starch. This suggests that acarbose considerably inhibits alpha-amylase, and not only brush-border enzymes. In vitro experiments confirm that an inhibition of two thirds of alpha-amylase activity can be expected from pharmacologically used doses of acarbose.

The prevalence of esophageal chest pain was studied prospectively in patients referred on an elective basis to a cardiac unit for suspected myocardial ischemia. A group of 248 consecutive patients without previously documented heart disease was admitted for elective diagnostic coronary angiography. The clinical history classified 185 patients as having anginal pain and the coronary angiogram was normal in 48 of them. In 37 of these 48 patients full esophageal testing was performed including 24-hr intraesophageal pH and pressure recordings with indication of chest pain episodes as well as a number of esophageal provocation tests, ie, acid perfusion, edrophonium stimulation, balloon distension, and ergonovine stimulation, all performed under continuous esophageal manometric and electrocardiographic monitoring. In 19 of these 37 patients, the familiar chest pain could be reproduced by esophageal provocative testing without ischemic ST-T segment alterations; six of these 19 patients had also a positive 24-hr pH and pressure recording. These data strongly suggest an esophageal origin of chest pain in half the patients with typical angina and a normal coronary angiogram.

The effect of intestinal bacteria on the interdigestive myoelectric complex (IDMEC) was studied by recordings of the electrical activity of the proximal and distal small bowel in fasting germ-free (n = 6), gnotobiotic (n = 7), and conventional (n = 6) rats in vivo. Germ-free and gnotobiotic rats were operated and studied in germ-free or gnotobiotic conditions. The IDMEC period (mean +/- SD) in the proximal and distal small bowel was significantly longer in germ-free rats (20 +/- 2 min and 102 +/- 14 min) as compared to conventional rats (13 +/- 1 min and 58 +/- 5 min). Association of germ-free rats with a limited flora (gnotobiotic rats) decreased the IDMEC period significantly (15 +/- 1.5 min and 75 +/- 14 min). The migration velocity of the IDMEC was inversely related to the IDMEC period. These observations confirm previous data suggesting that the interdigestive motor complex has a role in the homeostasis of the bacterial content of the small bowel.

In order to assess the possible role of the new candidate gut hormone, motilin, in controlling the interdigestive migrating motor complex (MMC) in man, 14 normal subjects were studied after an overnight fast by means of three pressure-recording catheters with orifices 25 cm apart in the upper small intestine. The typical aboral progressing bursts of pressure waves occurred at a mean interval of 137 minutes and were preceded by a peak motilin level 25 pmol/liter higher than the lowest level in the postactivity-front quiescent period. To study the effect of exogenous motilin, an infusion of pure porcine motilin at various dose levels was given to 16 normal volunteers shortly after the onset of the phase I quiescent period. Motilin infusion induced an activity front in 12 of the 16 subjects. The mean activity front interval was reduced to 46 min (P less than 0.001). This effect could be obtained even at the low dose level of 0.4 pmol/kg/min, which produced an increase in plasma motilin level of only 57 pmol/liter. These data suggest that a cyclic rise in plasma motilin levels is one of the factors involved in the production of the activity front of the migrating motor complex in man.

The efficacy and safety of omeprazole, 40 mg once daily for four to eight weeks of treatment, were studied in 61 patients with ulcerative reflux esophagitis. A double-blind controlled study design was used, and the patients were randomly allocated to treatment with either omeprazole 40 mg once daily or ranitidine 150 mg twice daily. Endoscopy was performed prior to inclusion into the study, after four weeks and, if unhealed, again after eight weeks. Healing of esophagitis was defined as complete disappearance of all esophageal ulcerations. Symptoms were recorded before entry, after four weeks, and again after eight weeks in unhealed patients. Fifty-one patients were included in the per-protocol analysis at day 29, and 50 patients at day 57. The healing rate after four weeks of treatment was 22 of 26 patients (85%) treated with omeprazole and 10 of 25 patients (40%) treated with ranitidine (P less than 0.001). The corresponding figures after eight weeks were 24 of 25 (96%), and 13 of 25 (52%) (P less than 0.001). These results were confirmed in the intent-to-treat analysis. Patients treated with omeprazole showed a significantly faster and more profound relief in heartburn than patients treated with ranitidine: 85% had no heartburn after four weeks of treatment with omeprazole compared to 24% in patients treated with ranitidine (P = 0.00007). The percentage of patients who were free of all reflux symptoms was significantly greater in the omeprazole-treated group as compared to the ranitidine-treated group (62% and 12% respectively; P = 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Arachis oil and a mixture of arachis oil with bile and pancreatic enzymes were infused into the duodenum and ileum of dogs via surgically positioned catheters in order to study the mechanism of disruption of the migrating complex by intraluminally infused triglycerides, the importance of cholecystokinin and neurotensin in this event, and the pattern of digestive myoelectrical activity during fat digestion. When infused into the duodenum both arachis oil and the oil-bile-pancreatic enzyme mixture disrupted the migrating myoelectric complex (MMC). When infused into the ileum, only the oil-bile-pancreatic enzyme mixture disrupted the MMC. The duration of the disruption lasted as long as when the same amount of oil was administered orally. Triglyceride-induced digestive activity was characterized by the frequent alternation of short periods of spiking activity and short periods of quiescence. It is concluded that the triglyceride-induced disruption of the MMC-pattern is not caused by the triglyceride itself but by some emulsion or digestion product. We further suggest that the disruption is hormonally mediated and due to fat-stimulated neurotensin, rather than cholecystokinin (CCK), release.

A 70-year-old woman with secretory diarrhea was studied with a novel technique of recording small intestinal myoelectrical activity which allowed us to obtain long, uninterrupted records of slow waves and spikes at eight or more different intestinal levels simultaneously. Typical migrating action potential complexes (MAPCs) were observed, consisting of spike bursts that extended over more than one slow wave and migrated distally at the same propagation velocity as the slow waves. This motility pattern occurred frequently during the period the patient presented with secretory diarrhea and disappeared with the disappearance of the diarrhea. It was observed only once in a series of 10 normal control subjects. This is the first report on MAPC activity in man and on the association of this myoelectrical pattern with secretory diarrhea in man.

The purpose of these experiments was to characterize the pattern of digestive myoelectric activity produced by four different test meals in dogs. A new approach for the analysis of the myoelectric activity of the small intestine was used. In contrast with methods dividing the tracings into present time periods, the present method respected the "motor entities," hence the continuity, of the tracing. Two types of motor entities occurred: "activity units" which are groups of consecutive slow waves with spiking, and "rest units," which are groups of consecutive slow waves without spiking. The frequency of occurrence and frequency of alternation of the various activity and rest units occurring during digestion was calculated. Digestive myoelectrical activity was characterized by the frequent occurrence and alternation of short activity and rest units. Three different patterns of digestive activity could be discriminated, ie, a fat, a protein and carbohydrate, and a canned food pattern.

The effects of interruption of the enterohepatic circulation of bile acids on biliary lipid secretion have only been studied experimentally, and quantitative data in patients are lacking. Therefore, biliary lipid secretion during steady-state meal perfusion of the duodenum was studied in six patients with partial ileocolectomy, five patients with Crohn's disease, and five normal subjects. Bile acid outputs in the resection patients were significantly lower than in normal controls, (6.87 +/- 2.10 mmol/6 hr and 13.5 +/- 2.16, respectively; P less than 0.001) and were also decreased in two of the five Crohn's disease patients. Bile acid outputs in patients with resection progressively decreased in the course of the perfusion study; phospholipid and cholesterol secretion did not decrease to the same extent, and cholesterol saturation gradually increased. Bile of these patients, therefore, was frequently supersaturated due to uncoupling of bile acid secretion and outputs of the other biliary lipids. Bile acid outputs, although decreased, did not reach very low values, which shows that the enterohepatic circulation was not totally interrupted. Chenodeoxycholic acid was the main bile acid component of bile in patients with ileocolonic resection. Deoxycholic acid was absent from bile of four resected patients and two Crohn's patients. Two patients with active Crohn's disease had low bile acid outputs despite only moderate fecal bile acid losses. Therefore, decreased outputs may be caused by decreased bile acid pool not compensated for by increased bile acid synthesis in severely ill patients.

Lipid composition of fasting duodenal bile was studied in 56 patients with nonoperated Crohn's disease, 21 normals matched for age and sex, 13 patients with cholesterol cholelithiasis, and 9 patients with ileal resections. Crohn's patients had a significantly higher mean saturation index, calculated according to Thomas (0.84 +/- 0.51) when compared to normal (0.63 +/- 0.25). Patients with ileocolonic Crohn's disease and patients with severe bile acid malabsorption, particularly, showed an increased incidence of cholesterol saturated bile. Saturation in patients with nonoperated Crohn's disease was not increased to the levels found in patients with ileal resection or cholesterol gallstones. Bile acid composition of gallbladder bile was characterized by a significant decrease of the deoxycholate fractions in patients with Crohn's ileocolitis and colitis as well as in ileal resected patients. These qualitative changes of bile acid composition may influence cholesterol solubility. It is concluded that patients with nonoperated Crohn's disease may have an increased risk of developing cholesterol gallstones.

The effects of cisapride on upper gut motility were studied in seven healthy volunteers by means of a novel intraluminal electromyographic technique in a placebo-controlled study. In the interdigestive state, cisapride (10 mg intravenous bolus injection) markedly increased the number of spike bursts. The most obvious effect was observed during the first 5-min period when a nonmigrating phase-3-like activity (stationary phase 3) occurred, which lasted for 2.6 +/- 0.4 min. This initial pattern was followed by an intense phase 2 activity, characterized by a 10-fold increase in the number of groups of repetitive spike bursts and a sixfold increase in the number of ultrarapid single propagated spike bursts (ultrarapid peristaltic rushes). Cisapride induces in the human upper gut a remarkable pattern of aborally propagated (peristaltic) contractions, which are very likely responsible for the active propulsion of intestinal contents in the interdigestive state.

A classification of gastrointestinal motility disorders is offered based upon the type of disorder in transit (delay or acceleration), and the region of the gastrointestinal tract affected. Specific abnormalities of myoelectrical patterns are identified when possible and related to disturbances in transit in the stomach and small bowel.