Carlos Defilippi

Long-term treatment with cisapride and antibiotics in liver cirrhosis: effect on small intestinal motility, bacterial overgrowth, and liver function

OBJECTIVES:Altered small-bowel motility, lengthening of the orocecal transit time, and small-intestinal bacterial overgrowth have been described in patients with liver cirrhosis. These changes might be related to the progressive course and poor prognosis of the disease. We investigated the effect of a long-term treatment with cisapride and an antibiotic regimen on small-intestinal motor activity, orocecal transit time, bacterial overgrowth, and some parameters of liver function.METHODS:Thirty-four patients with liver cirrhosis of different etiology entered in the study. They were randomly allocated to receive cisapride (12), an alternating regimen of norfloxacin and neomycin (12), or placebo (10) during a period of 6 months. At entry and at 3 and 6 months, a stationary small-intestinal manometry was performed, and orocecal transit time and small-intestinal bacterial overgrowth were also investigated using the H2 breath test. Liver function was estimated with clinical and laboratory measurements (Child-Pugh score).RESULTS:After 6 months, both cisapride and antibiotics significantly improved fasting cyclic activity, reduced the duration of orocecal transit time, and decreased small-intestinal bacterial overgrowth. Cisapride administration was followed also by an increase in the amplitude of contractions. No statistically significant variations in these parameters were observed with placebo. An improvement of liver function was observed at 3 and 6 months with both cisapride and antibiotics.CONCLUSIONS:Long-term treatment with cisapride or antibiotics reversed altered small-intestinal motility and bacterial overgrowth in patients with liver cirrhosis. These findings suggest a possible role for prokinetics and antibiotics as a modality of treatment in selected cases of decompensated cirrhosis.

Altered Small Bowel Motility in Patients with Liver Cirrhosis Depends on Severity of Liver Disease

Abnormal small bowel motility has been describedin patients with liver cirrhosis but the mechanismsinvolved are unknown. The aim was to investigate apossible relationship between the severity of liver failure and the intensity of small intestinalabnormalities. Motility was studied during fasting, bymeans of perfused catheters and external transducers, on33 cirrhotics with different etiologies; 8 were at Child-Pugh stage A, 12 stage B, and 13 stageC. Both abnormalities of MMC and increased clusteredactivity were recorded. Absence of cycling activity wasmost frequently observed in Child-Pugh stage C patients compared to Child-Pugh stage Acirrhotics. A significant increase in clusteredcontractions from 4.7 ± 0.4/hr in stage Apatients to 11.3 ± 1.1 in stage C was recorded.The frequency and amplitude of contractions was also increased fromChild-Pugh stage A to stage C. Our findings might berelated to a delayed transit time observed in thesepatients and a higher prevalence of bacterial overgrowth in cirrhotics with more advanced liverdisease.

Inhibition of Gastric Emptying in Humans by Secretin, the Octapeptide of Cholecystokinin, and Intraduodenal Fat

Intraduodenal fat is a potent inhibitor of gastric emptying. Neural and hormonal mechanisms are probably involved. Secretin and cholecystokinin are among the hormones known to be released by fat in the intestine. In this study we investigated the effect of the octapeptide of cholecystokinin, secretin, and intraduodenal oleate on the inhibition of gastric emptying of liquids in humans. On different days the gastric emptying of a 250-ml saline meal was studied in 6 healthy volunteers under the following conditions: (a) during graded doses of the cholecystokinin-octapeptide alone; (b) during graded doses of secretin; (c) during graded doses of secretin with a background of the cholecystokinin-octapeptide; and (d) during intraduodenal oleate perfusion. All the subjects were also studied for pancreatic enzyme secretion in response to the hormones and intraduodenal oieate. With a secretin background, the octapeptide of cholecystokinin was a potent stimulant of pancreatic secretion; while alone, only the highest dose significantly delayed gastric emptying. Secretin at doses of 2.5 pmol kg -1 · h -1 and higher significantly inhibited gastric emptying (p

Manometric Studies on the Human Pyloric Sphincter: Effect of cigarette smoking, metoclopramide, and atropine

Pyloric sphincter pressure was assessed with water-perfused polyvinyl tubes. Smoking one cigarette significantly decreased the basal pyloric pressure, whereas 10 mg of metoclopramide as an intravenous bolus increased the pyloric pressure in normal subjects and in patients with gastric ulcer with low basal pressure. Duodenal acidification with 0.1 N HCl significantly increased pyloric pressure. Atropine 15 mug per kg, subcutaneously prevented the rise of pyloric pressure in response to acid infusion into the duodenum.

Small Intestinal Clustered Contractions and Bacterial Overgrowth: A Frequent Finding in Obese Patients

BackgroundSmall intestinal bacterial overgrowth (SIBO) has been observed in several disorders of the gastrointestinal tract. Studies have shown abnormalities of motor function in obese patients, and there is indirect evidence suggesting that SIBO is present in them.AimsTo study small intestinal motility and the prevalence of SIBO in obese patients and to determine whether there was any relationship between both parameters.MethodsThirty-nine patients scheduled for bariatric surgery were subjected to hydrogen breath test with lactulose and to a stationary small intestinal motility study with perfused catheters.ResultsSIBO was observed in 41% of obese patients and was not related to body mass index. Small intestinal manometry showed a marked increase of clustered contractions in obese patients with SIBO compared to obese subjects without SIBO, whereas all the other parameters of fasting cyclic activity were not different.ConclusionsSIBO was a frequent finding in obese patients and was associated with an increased pattern of clustered contractions, which was not observed in absence of SIBO.

Pyloric-sphincter studies in peptic-ulcer patients

Pyloric pressure was assayed by a manometric procedure in the basal state and after intraduodenal infusion of HCl. 13 control subjects, 11 patients with benign gastric ulcer, 8 with duodenal ulcer, and 2 with coexistent gastric and duodenal ulcers were studied. Mean resting pyloric pressure in gastric-ulcer patients (5.17±0.71) mm Hg) was significantly lower than controls (9.40±0.85 mm Hg) and did not increase after HCl perfusion into the duodenum. Mean basal pyloric pressure in duodenal-ulcer patients (11.30±1.57 mm Hg) did not differ significantly from controls and increased after intraduodenal perfusion of HCl to 15.72±2.40 mm Hg. The two patients with coexistent ulcers had manometric patterns similar to gastric-ulcer patients. Decreased pyloric-sphincter pressure in gastric-ulcer patients may be the mechanism responsible for the increased duodeno-gastric reflux observed in these patients.

Small bowel motility in primary biliary cirrhosis

Objective:Previous studies have shown small bowel motor activity abnormalities in patients with liver cirrhosis of different etiologies, but motility has not been studied in patients with primary biliary cirrhosis. Our aim was to investigate proximal small bowel motility in these patients.Methods:Twenty-five female patients presenting clinical, biochemical, serological, and histological findings compatible with primary biliary cirrhosis, 10 female patients with nonalcoholic liver cirrhosis, and 10 normal female controls were studied. Motility of the upper small bowel was measured in the fasted state by means of perfused manometric catheters, connected to external transducers and positioned in the small bowel under fluoroscopy.Results:The average amplitude of contractions was significantly decreased in patients with primary biliary cirrhosis compared with other liver cirrhosis (20.2 ± 1.0 vs 32 ± 2.9 mm Hg). Also, a significantly increased frequency of cluster of contractions and an increased duration of phase II of the migrating motor complex as seen in liver cirrhosis was observed when compared with normals.Conclusions:We conclude that primary biliary cirrhosis patients present motor abnormalities of the small intestine similar to those of patients with liver cirrhosis of other etiologies. In addition, a decrease in the amplitude of small bowel contractions was also found in these patients, suggesting a myogenic involvement.

Effect of casein and casein hydrolysate on small bowel motility and D-xylose absorption in dogs.

Abstract Food administration is followed by the appearance of a small intestinal pattern of irregular contractions. Studies on the relationship between intestinal motor activity, transit and absorption have yielded contradictory results. Since previous studies have shown that casein and casein hydrolysate led to a decrease of small intestinal motor activity and transit, the aim was to evaluate the effect of these nutrients on small intestinal motility and D‐Xylose absorption. Studies were performed in five dogs with a duodenal fistula; motility was recorded by means of six infused catheters and external transducers. Three test solutions with the same osmolality, lactulose, casein and casein hydrolysate, were continuously infused through the duodenal cannula. D‐Xylose was injected in the duodenum and plasma levels determined at regular intervals. Absorption of D‐Xylose was greatest during the administration of casein hydrolysate, the lowest levels were seen with lactulose and intermediate levels were obtained with casein. The effect of casein hydrolysate on small intestinal motility was characterized by a decrease in the frequency of contractions. Propulsive contractions were decreased after the infusion of both casein and casein hydrolysate. Lactulose infusion was followed by the greatest motor activity of both frequency and propulsive contractions. These results suggest that the motor patterns observed with casein and casein hydrolysate lead to increased intestinal absorption of D‐Xylose.

Relationship between antropyloric and intestinal motility and duodenogastric reflux in fasting dogs

Duodenogastric reflux was studied in fasting dogs with gastric and duodenal cannulae, by means of recovery from the gastric cannula of phenol red infused into the duodenum and bile acids recovered from the gastric cannula. Simultaneously, antropyloric and intestinal motility was studied in order to establish a relationship between motility and duodenogastric reflux. A different pattern of duodenogastric reflux was observed, depending on the method utilized. While a significantly higher reflux was observed during phase II in bile acid studies, an irregular pattern not related to the different phases of the interdigestive motor complex was observed in experiments with phenol red. Antral motility estimated by an antral motility index showed a statistically significant correlation with DGR estimated by both methods. Pyloric pressure and intestinal motility did not show a correlation with DGR. We concluded that the results obtained in studying duodenogastric reflux depend on the method used. The main factor related to increased duodenogastric reflux was the decreased antral motility.

Nonsteroidal antiinflammatory drugs: Effect on pyloric sphincter and duodenogastric reflux

We have investigated the effect of nonsteroidal antiinflammatory drugs on canine pyloric sphincter pressure, mucosal potential difference (PD), and duodenogastric reflux in 5 dogs. Only intragastric aspirin at doses of 30 and 100 mg/kg caused a significant (P<0.05) decrease in pyloric sphincter pressure, an increase of duodenogastric reflux, and changed the mucosal PD. Neither intravenous aspirin, intragastric phenylbutazone, or intrarectal indomethacin produced these changes. The mechanism for the aspirin effect may be mediated by local pathways related to changes in mucosal PD. We postulate that increased duodenogastric reflux may be an aggravating factor for the gastric mucosal damage caused by intragastric aspirin.