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Background & Aims: Intrasphincteric injection of botulinum toxin has been suggested as an alternative treatment modality in esophageal achalasia. A controlled trial comparing botulinum toxin, placebo, and pneumatic dilation is reported., Methods: Sixteen patients received random intrasphincteric injections of either botulinum toxin or saline. The efficacy of treatment was assessed by symptom score, esophageal manometry, and scintigraphy. In case of failure, pneumatic dilation was performed., Results: One month after injection, symptoms had improved in all patients treated with botulinum toxin (symptom score, 0.9 +/- 0.6 vs. 5.5 +/- 1.4; P < 0.02). In the placebo group, symptoms were unchanged in all patients, who were all dilated. Lower esophageal sphincter pressure decreased by 49% after treatment with botulinum toxin (P < 0.03) and by 72% after dilation (P < 0.01). Similarly, esophageal retention decreased by 47% after treatment with botulinum toxin (P < 0.02) and by 59% after dilation (P < 0.02). No significant difference in symptom score and esophageal function test results was found between patients treated with botulinum toxin injections and those undergoing dilation. However, 7 of the 8 patients in the botulinum toxin group required a second injection because of recurrent dysphagia., Conclusions: Treatment of achalasia with botulinum toxin was as effective as pneumatic dilation in relieving symptoms and improving esophageal function. The effect of the first injection was temporary, but the effect of the second injection lasted longer.

Background & Aims: Gastroesophageal reflux frequently occurs during spontaneous transient lower esophageal sphincter relaxations (TLESRs). The aim of this study was to determine the motor activity in the body of the esophagus during TLESRs in 10 healthy subjects., Methods: Esophageal contractions were recorded 13,8,and 3 cm above a sleeve that measured LES pressure. A balloon was inflated 8 cm above the sleeve to induce an esophageal tonic contraction (artificial high-pressure zone)., Results: No relaxation of the artificial high-pressure zone was detected at the onset or during spontaneous TLESRs before gastroesophageal reflux. Esophageal acidification provoked no changes or increased the pressure in the artificial high-pressure zone by 47.9% +/- 12% When gastroesophageal reflux abruptly distended the esophagus (common cavity), a relaxation of the artificial high-pressure zone of 51.1% +/- 6.6% was observed in 78% of the instances. Deglutitive or secondary contractions during spontaneous TLESRs traveled down the esophagus in 96.5% of the instances., Conclusions: Stimuli that induced spontaneous TLESRs did not by themselves inhibit muscle contractility in the body of the esophagus. Acidification without distention of the lower esophagus frequently increased esophageal tonic contractility. Abrupt lower esophageal distention by reflux of air or acid partially relaxed the artificial high-pressure zone in the esophageal body, probably to assist gastric venting.

Background/aims: Defining risk factors for ulcerative colitis (UC) is important to better understand the pathogenesis of this idiopathic disease. One factor modulating the disease is smoking. A pilot study showed the absence of appendectomy in the medical history of patients with ulcerative colitis. The aim of the present case control study was to compare the relative risk of developing UC after appendectomy with the relative risk of developing UC with an intact appendix., Methods: One hundred seventy-four (84 females and 90 males, mean age 34.9 years) consecutive UC patients examined at our inflammatory bowel disease clinic or hospital ward, were included. Fifty-six had pancolitis (32%) and 118 (68%) suffered from left-sided colitis. The control group consisted of 161 consecutive patients examined at the orthopedic clinic (86 females and 75 males, mean age 40.9 years)., Results: Two parameters, absence of appendectomy and smoking, were closely related to the development of UC. Before the onset of UC, only 1 of the 174 patients (0.6%) had undergone an appendectomy. Of the 161 controls, 41 (25.4%) had undergone an appendectomy. The difference between the two groups was highly significant with an odds ratio of 59.1 (95% CI, 18-189; P < 0.001). The relative risk of getting the disease associated with nonsmoking was 2.95 (95% CI, 1.69-5.17)., Conclusions: Appendectomy is a protective factor against UC.

Background/aims: Primary esophageal motility disorders (achalasia, diffuse esophageal spasm, and intermediate forms) are suggested to be caused by different degrees of inhibitory dysfunction; however, direct evidence for this hypothesis has never been presented in humans. The aim of this study was to measure the degree of inhibition that precedes deglutitive contractions in patients with primary motility disorders., Methods: Deglutitive inhibition was examined in patients with primary motility disorders: 9 with achalasia, 6 with symptomatic diffuse esophageal spasm, and 5 with intermediate forms. An artificial high-pressure zone was created in the esophageal body by inflating a balloon to a critical level, and pressure changes were measured at the interface between the balloon and esophageal wall. Inhibition was visualized as a relaxation of the artificial high-pressure zone., Results: An inverse relationship was found between the degree of inhibition and the propagation velocity of the deglutitive contraction (r = 0.75; P < 0.001). Normally propagated contractions were preceded by an inhibition of 84.2% +/- 3.6%; fast-propagating contractions were preceded by partial inhibition of 40.6% +/- 6.2%; and, in case of simultaneous contractions, inhibition was absent, i.e., 2.6% +/- 1.6%., Conclusions: The spectrum of primary motility disorders is an expression of a progressively failing deglutitive inhibition.

Background: 5-hydroxytryptamine-3 (5-HT3) receptor antagonists inhibit gastric phase-3 motor activity in the dog. This study examined the role of 5-HT3 receptors in the generation of gastric phase 3 of the migrating motor complex in humans., Methods: Interdigestive motor activity was recorded manometrically in 16 subjects before and after administration of ondansetron, a selective 5-HT3 receptor antagonist. Plasma motilin values were also assayed in 7 individuals. The incidence of gastric activity fronts before and after ondansetron was compared with a control group that had not received ondansetron. The ability of erythromycin to induce a gastric activity front in the presence of ondansetron was also evaluated in 7 subjects., Results: The incidence of gastric activity fronts was 69% before ondansetron vs. 19% after ondansetron. In contrast, in the control group there was no significant change in the incidence of gastric activity fronts over time. Activity fronts preceding ondansetron were associated with motilin peaks while activity fronts after ondansetron were not. Despite the previous administration of ondansetron, erythromycin induced gastric activity fronts in 89% of cases., Conclusions: Selective antagonism of 5-HT3 receptors suppresses the gastric component of phase-3 motor activity and simultaneously suppresses plasma motilin peaks. The results suggest that the suppression of gastric activity fronts is achieved via the suppression of plasma motilin peaks because in the presence of ondansetron a motilin agonist like erythromycin restores the gastric phase 3.

Background: The aim of the present study was to develop a breath test for measuring gastric emptying rate of solids that would induce less radiation exposure than radioscintigraphy and would be applicable to field testing., Methods: A test meal was used in which [14C]-octanoic acid was mixed with egg yolk and prepared as a scrambled egg. The test meal was labeled with a second marker, 99mTc-albumin colloid, and simultaneous radioscintigraphic and breath test measurements were performed in 36 subjects, 16 normal controls, and 20 patients with dyspeptic symptoms. Mathematical analysis of the excretion rate of labeled CO2 resulted in the definition of three parameters, i.e., gastric emptying coefficient, gastric half-emptying time, and lag phase., Results: There was an excellent correlation between the gastric emptying coefficient and the scintigraphic half-emptying time (r = -0.88); between the half-emptying time determined by the breath test and the scintigraphic half-emptying time (r = 0.89); and between the lag phases determined by scintigraphy and those determined by breath test (r = 0.92). 14C can be replaced by 13C for labeling the octanoic acid used in the breath test., Conclusions: It is concluded that the octanoic acid breath test is a reliable noninvasive test to measure gastric emptying rate of solids.

Animal studies have shown that primary esophageal peristalsis is preceded by a wave of inhibition spreading rapidly down the esophagus and lasting longer in more distal segments. In humans, its presence in the esophageal body cannot be demonstrated manometrically because of the absence of tone. To study deglutitive inhibition in humans, an artificial high-pressure zone was created by inflating an intraesophageal balloon to a critical level. The pressure changes at the interface between the balloon and the esophageal wall at various levels along the esophagus were measured. In this artificial high-pressure zone, deglutition induced a relaxation beginning simultaneously at various levels of the esophagus but lasting progressively longer in progressively more distal segments. Latency from onset of deglutition to onset of relaxation at 13 cm and 8 cm above the lower esophageal sphincter and at the lower esophageal sphincter was 0.06 +/- 0.19 seconds, 0.10 +/- 0.31 seconds, and 0.89 +/- 0.53 seconds, respectively; latency to contraction was 4.45 +/- 0.54 seconds, 6.04 +/- 0.79 seconds, and 9.14 +/- 1.04 seconds, respectively. This is the first direct evidence that deglutition produces in the human esophagus a wave of inhibition that precedes the primary peristaltic contraction.

Widespread alterations of the gut autonomic nervous system have been described in Crohn's disease. Immunohistochemistry shows that these alterations are associated with the expression of major histocompatibility (MHC) class II antigens (HLA-DR) on enteroglial cells in the ganglia of the submucous and myenteric plexuses and on the enteroglial sheaths of the nerve extensions. Neuronal cell bodies and extensions do not express MHC class II antigens. The class II expression is associated with the presence of UCHL1-positive T lymphocytes. MHC class II expression can also be found on endothelial cells and vascular smooth muscle cells but not on smooth muscle cells of the muscularis mucosae or propria. The intensity of MHC class II expression on the glial cells of the enteric nervous plexus and on endothelial cells correlates well with the intensity of class II expression on epithelial cells.

The effect of three doses of erythromycin on interdigestive gastrointestinal motility and on plasma motilin levels was studied in healthy volunteers and patients with diabetic gastroparesis. Abnormalities of interdigestive motility were observed in 40% of the patients. In healthy volunteers, 40 mg erythromycin elicited a premature phase 3 that started in the stomach. In contrast to the spontaneous gastric phase 3, this erythromycin-induced phase 3 was not accompanied by a motilin peak. In patients with diabetic gastroparesis, 40 mg erythromycin induced a premature phase 3 in three patients, no response in one patient, and a burst of antral contractions in another patient. Doses of 200 and 350 mg erythromycin elicited a burst of antral phase-3-like contractions in both volunteers and patients, which was not accompanied by a motilin peak. This phase-3-like activity did not migrate to the small intestine and was not followed by a phase 1, but by a prolonged period of antral contractile activity. The number and amplitude of antral contractions after 200 or 350 mg erythromycin were significantly higher than after 40 mg. The motor patterns induced by different doses of erythromycin offer potential therapeutic applications.

Erythromycin has been shown to act as a motilin agonist by binding to motilin receptors on gastrointestinal smooth muscle and to improve the severely impaired gastric emptying in patients with diabetic gastroparesis. To elucidate the motor pattern that accounts for this accelerated emptying, the effect of 200 mg erythromycin vs. placebo on postprandial motility of the stomach and the upper small intestine was examined in 13 normal subjects. Erythromycin significantly increased the amplitude of the antral contractions during the 2-hour postprandial study period (maximal difference in mean amplitude of distal antral contractions between erythromycin and placebo recorded from 80 to 90 minutes after meal: 123 +/- 17 vs. 44 +/- 12 mm Hg; P less than 0.005). The total number of antral contractions was not affected, but the contractions could be recorded manometrically higher up in the stomach after erythromycin than after placebo (9-12 vs. 3-6 cm above the pylorus). Antroduodenal coordination was significantly improved during the first postprandial hour, and the first normal phase 3 of the migrating motor complex, indicating the reappearance of fasting motility, occurred earlier after erythromycin than after placebo (128.3 +/- 14.3 vs. 173.4 +/- 16.1 minutes; P less than 0.05). These changes in postprandial motility induced by erythromycin may well account for its accelerating effect on gastric emptying.

Erythromycin markedly accelerates gastric emptying, possibly because it acts as a motilin agonist. In the present study, the effect of an equipotent dose of motilin was tested. In six patients with severe diabetic gastroparesis, gastric emptying of liquids and solids was examined scintigraphically after motilin or placebo in a double-blind crossover study. Motilin (10 pmol.kg-1.min-1) or saline was infused over a 90-minute period starting 5 minutes before breakfast. Motilin markedly accelerated emptying. For liquids, the half-emptying time was reduced from 51 +/- 6 to 22 +/- 11 minutes (P less than 0.01) and for solids from 111 +/- 4 to 51 +/- 12 minutes (P less than 0.01). The mean increase in plasma motilin levels was 1315 +/- 342 pg/mL, corresponding to an effective infusion rate of about 4 pmol.kg-1.min-1. In the control experiments, basal motilin levels (173 +/- 17 pg/mL) were within the normal range but increased steadily postprandially, reaching 321 +/- 25 pg/mL at the end of the study period, probably reflecting gastric distension. The postprandial increase in pancreatic polypeptide level was blunted compared with accepted normal values but was more pronounced during motilin infusion, i.e., 650 +/- 217 vs. 279 +/- 66 pg/mL (P less than 0.01), probably because of the improved emptying. Our data show that motilin accelerates gastric emptying in diabetic gastroparesis and support the hypothesis that erythromycin's effect is mediated through motilin receptors.

Patients with Roux-en-Y anastomoses may have chronic symptoms of nausea, vomiting, epigastric fullness, and abdominal pain. To investigate the mechanism of these symptoms, the electrical activity of the Roux limb was studied in five symptomatic and four asymptomatic patients with Roux-en-Y anastomoses. Slow-wave and spike activity in the Roux limb were recorded using six bipolar suction electrodes positioned 10 cm apart. Ten healthy volunteers were studied as a control. In the control subjects, the mean slow-wave frequency decreased from 11.27 +/- 0.2 cycles/min at 30 cm below the ligament of Treitz to 10.96 +/- 0.2 cycles/min at 80 cm past Treitz. By contrast, in five patients the slow-wave frequency in the Roux limb increased from 11.12 +/- 0.2 cycles/min 10 cm below the gastrojejunal anastomosis to 11.42 +/- 0.4 cycles/min 50 cm more distally. Four of these five patients had severe symptoms. In the other four patients, of whom three were completely symptom-free, an aborally decreasing slow-wave frequency was observed. In both the controls and the patients with Roux-en-Y anastomoses, the direction of propagation of phase 3 spike bursts of the migrating motor complex was always aboral. During phase 2, most spike bursts were uncoordinated at adjacent recording sites. Propagated spike bursts, single or repetitive, were rare. The propagation direction of these spike bursts was always aboral in healthy controls. In symptomatic patients with inverted slow wave frequency gradients, however, the rare propagated spike bursts always propagated orally. The observed electrical abnormalities may in part be responsible for the symptoms of patients with the Roux-en-Y syndrome.

The influence of metabolic substrates on the formation of volatile compounds by the colonic flora was measured in a fecal incubation system. The presence of carbohydrates (0, 25, and 50 mg/20 mL fecal suspension) led to a dose-related increase in the formation of alcohols and H2 and to a dose-related decrease in the formation of toxic mercaptans. This effect seemed to be independent of pH. The presence of albumin or fat (50 mg/20 mL fecal suspension) as substrates for the colonic flora gave rise to the formation of significantly higher amounts of methanethiol. Small amounts of pentane were found in the headspace after incubation with oil. These data show that the formation of volatile metabolites by the colonic flora is greatly influenced by the available substrates.

Eighty-nine patients who had been treated by ileal resection for Crohn's disease between 1979 and 1984 were included in a prospective cohort follow up to study the natural course of early postoperative lesions. Recurrent lesions were observed endoscopically in the neoterminal ileum within 1 year of surgery in 73% of the patients, although only 20% of the patients had symptoms. Three years after surgery, the endoscopic recurrence rate had increased to 85% and symptomatic recurrence occurred in 34%. The ultimate course of the disease was best predicted by the severity of the early postoperative lesions, as observed at ileoscopy. Clinical parameters that influenced outcome were preoperative disease activity, the indication for surgery, and the number of surgical resections. When patients were stratified for preoperative disease activity, the severity of lesions found at endoscopy remained a strong predictive factor for symptomatic recurrence. In 22 other patients submitted to "curative" ileal resection and ileocolonic anastomosis, the segment to be used as neoterminal ileum was carefully examined during surgery, and two large biopsies were taken before making the anastomosis. An ileoscopy was performed 6 months after surgery. Although all patients had a macroscopically normal neoterminal ileum and 19 had entirely normal biopsies at the time of surgery, 21 patients were found at ileoscopy to have developed ileitis involving a 15-cm segment (range, 4-30 cm), and 20 had unequivocal microscopic lesions on biopsies. These studies suggest that early lesions in the neoterminal ileum after Crohn's resection do not originate from microscopic inflammation present in this bowel segment at the time of surgery. The early postoperative lesions in the neoterminal ileum seem to be a suitable model to study the pathogenesis of Crohn's disease and also to evaluate new therapeutic modalities, either to prevent development of these early lesions or to treat progressive recurrence.

The development of the motilin receptor was studied through contraction and binding studies of groups of three rabbits aged between 2 and 289 days. The contractility of small intestinal smooth muscle strips was measured isotonically. The aborally decreasing gradient in response to motilin, known to exist in adult rabbits, was already present at day 8 (maximum contractile responses expressed as a percent of the maximal response to acetylcholine were 77% +/- 9%, 34% +/- 10%, and 25% +/- 8% for duodenal, jejunal, and ileal strips, respectively). Throughout the observation period, the doses of motilin and its agonist erythromycin that were required to induce 50% of the response remained constant and were not significantly different from doses required for adults (their negative logarithms were 8.55 +/- 0.35 and 5.70 +/- 0.25, respectively). The correlation between the maximum contractile response toward motilin and erythromycin was almost perfect (r2 = 0.82). Binding studies with iodinated norleucine13-porcine motilin were performed using antral smooth muscle tissue homogenates. The maximum number of binding sites increased rapidly after 8 days (3.3 +/- 0.4 fmol/mg protein) and reached a peak at 21 days (20.7 +/- 1.4 fmol/mg protein), but decreased at that point toward the adult value (40 days, 10.6 +/- 1.3; 289 days, 9.8 +/- 1.1 fmol/mg protein). The dissociation constant, however, remained unchanged. The peak value of receptor density occurred at about the time that the rate of increase of the length of the intestine and of the weight of the antrum were at maximum levels (at 18 and 27 days, respectively). Motilin receptors are expressed early postnatally, and the regional gradient in sensitivity towards motilin is also established soon after birth. If applicable to humans, an early response to erythromycin may have therapeutic value.

From 1972 to 1977, the authors observed 156 patients with primary esophageal motility disorders which caused such a severe degree of dysphagia that treatment by pneumatic dilatation was deemed necessary. Before dilatation, 24% of the patients presented with motility disorders that did not fit well into the two classical disease entities, diffuse esophageal spasm and achalasia (absence of peristalsis with presence of lower esophageal sphincter (LES) relaxations or presence of peristalsis with absence of LES relaxations). After treatment with pneumatic dilatation, these "intermediate" forms constituted 45% of the motor disorders. This was due mainly to the reappearance, on manometric tracings, of peristaltic contractions and of LES relaxations. Radiologic and manometric observations suggest that in many patients, this "return of peristalsis" may be an apparent change in pressure pattern rather than a real change in motility. In 6 of the 156 patients, a deterioration of the esophageal motility disorder was observed, which was characterized by the loss of peristalsis and of LES relaxations over a period of a few months or years. The frequent occurrence of intermediate types of motility disorders and the transition from diffuse spasm to achalasia suggest that achalasia and diffuse esophageal spasm are part of a spectrum of related motor disorders.

Sixty patients with anginalike chest pain of noncardiac origin were studied to determine the diagnostic value of 24-h ambulatory esophageal pH and pressure monitoring. The results of these 24-h studies were compared with those obtained by established methods, including x-rays, endoscopy with biopsy, conventional esophageal manometry, and acid perfusion test. Esophageal origin of the chest pain was considered to be likely if the familiar pain sensation was reproduced by the acid perfusion test, or if the pain occurred during an episode of gastroesophageal reflux, severe motor disorders, or both. When the results of established methods were combined and interpreted according to predetermined criteria, esophageal origin of the pain was shown to be likely in 27% of the patients. The 24-h recordings, alone, showed the esophagus to be the likely cause of the pain in 35% of the patients. Combination of all conventional examinations and of 24-h recordings made esophageal origin of the pain likely in 48% of the patients.

A multicenter study was conducted on 173 patients with active, endoscopically proven duodenal ulcers (158 men, 15 women). They were randomly assigned, in a double-blind manner, to two groups: those receiving placebo capsules (91 patients) and those receiving capsules containing 100 microgram of 15(R)-15-methyl prostaglandin E2 (arbaprostil) (82 patients). Each drug was ingested four times a day (1 h before meals and at bedtime) for 28 days. Endoscopy was performed on days 0, 14, and 28 after the trial began. At each examination, the ulcer size was measured and whether the ulcer had healed was recorded. Arbaprostil increased the incidence of ulcer healing to approximately the same degree as reported in most extensive studies with cimetidine. At 14 days, three times as many patients were totally healed in the arbaprostil-treated as in the placebo-treated group (37% vs. 12%, p less than 0.001). At 28 days, 67% of patients receiving arbaprostil were healed compared with 39% in the group receiving placebo (p less than 0.001). Similarly, the ulcer size, measured endoscopically, was much smaller after arbaprostil administration than in the group receiving placebo after both 14 and 28 days (p less than 0.001). Side effects attributable to treatment consisted primarily of loose stools and diarrhea (34%). Smoking retarded healing in the placebo-treated group (p less than 0.05), but did not significantly retard healing in patients treated with arbaprostil. We conclude that arbaprostil markedly accelerates the healing rate of active duodenal ulcers. This effect may be due to inhibition of acid secretion as well as gastric cytoprotection.

Four patients who developed acute viral hepatitis in the course of active Crohn's disease are reported upon. Three of these patients (1 with hepatitis A and 2 with hepatitis B) had a very striking and unusual clinical remission or apparent healing on regression of the hepatitis. These observations suggest that intercurrent hepatitis may have a beneficial effect on the course of active Crohn's disease.

Fluctuations of plasma motilin and gastrin levels were analyzed in relation to the interdigestive motor complex in humans, taking the onset of a duodenal activity front (phase 3 of the complex) as a reference point and the time lapse between two fronts as a time base. Statistical analysis showed a close relation between motilin fluctuations and the occurrence of duodenal activity fronts.

To study the peripheral effect of somatostatin in dogs a tiny Silastic catheter was implanted in an almost terminal branch of the mesenteric artery, providing blood supply to a jejunal segment of 5-10 cm. In 4 dogs one catheter was implanted, perfusing a small bowel segment about 60 cm below the angle of Treitz; in 3 dogs two catheters were implanted, perfusing two small bowel segments about 30 and 60 cm below the angle of Treitz. The catheter was kept open by continuous perfusion with a diluted heparin solution by means of a portable insulin infusion pump fixed to the animal's protection jacket. Small bowel motility was recorded electromyographically. Experiments were started 2 wk after surgery and were performed in conscious fasted animals. Control experiments using intraarterial saline perfusion showed normal migrating motor complexes in the perfused segment. Intraarterial perfusion of somatostatin (50-200 ng/kg X h) induced ectopic activity fronts, which always started just distal to the perfused segment and progressed down the small bowel at a normal propagation velocity. During the occurrence of ectopic fronts no activity fronts were observed in the small bowel proximal to the perfusion site. Apart from ectopic fronts, normal activity fronts, starting in the duodenum and passing the perfused segment, were also observed. The most proximal part of the jejunum was more sensitive to intraarterial somatostatin than the more distal jejunum. Intravenous infusion of the same doses of somatostatin had no effect. Somatostatin, therefore, seems to induce ectopic fronts via a local mechanism. We propose that somatostatin is able to relieve the intestine locally from an inhibitory mechanism that prevents the development of activity fronts.

A trial of neodymium-yttrium-aluminum-garnet laser treatment was conducted in 152 patients with upper gastrointestinal hemorrhage. Laser photocoagulation was applied in 0.5- to 1-s pulses of 55-80 W power. A first part of the trial studying patients with arterial bleeding was uncontrolled. Spurting arterial bleedings could be stopped in 87% of the 23 patients with acute arterial hemorrhage. The recurrence rate after endoscopic treatment of this type of bleeding was high (55%). The operation rate of 61% was, however, lower than the operative indications amounting to 95% in patients with arterial spurters admitted previously to our department. One hundred twenty-nine patients were included in a controlled randomized trial of laser photocoagulation. In 86 patients with active, nonspurting bleeding, the laser was significantly better (p less than 0.001) at stopping the bleeding than conservative treatment in randomized controls, and there was a numerical although not significant reduction of the rate of bleeding recurrence and the necessity for surgery (both p less than 0.1). In 43 patients with fresh stigmata of bleeding (i.e., fresh clot or visible vessel) laser treatment resulted in a numerical reduction in the rate of rebleeding and in the operative indications, but the difference did not reach statistical significance. The mortality rates were not influenced in any of the groups.

The influence of acoustic stress on postprandial gastrointestinal motility, gastric emptying, and plasma gastrin, pancreatic polypeptide, motilin, and somatostatin was evaluated in conscious dogs. Six dogs were equipped with strain-gauge transducers and were exposed from 1-3 h after the meal to prerecorded music (80-90 dB broad frequency noise), which produced a significant (p less than or equal to 0.05) lengthening of the gastric (31.2%) and jejunal (37.0%) postprandial pattern. In 4 other dogs with gastric cannula, a 2-h session of acoustic stress beginning just after eating a radiolabeled standard meal induced a slowing of gastric emptying of both liquid (45.7%) and solid (47.1%) phases of the test meal when measured 0.5 h after feeding. In contrast, when measured 2 h after feeding, similar values of gastric emptying of liquids and solids were observed in stressed and control animals. Compared with controls, the postprandial increases of plasma gastrin and pancreatic polypeptide levels were significantly enhanced in stressed animals and occurred early (15 min after the meal). Although postprandial decrease in plasma motilin was unchanged by acoustic stress, the rise in plasma somatostatin level was significantly (p less than or equal to 0.05) prolonged in stressed dogs. These results indicate that acoustic stress affects gastric and intestinal postprandial motility in dogs, delaying the recovery of the migrating motor complex pattern, inducing a transient slowing of gastric emptying, and enhancing the feeding-induced release of gastrin, pancreatic polypeptide, and somatostatin. Such hormonal changes might be due to a direct effect of stress rather than being the consequence of acoustic stress-induced slowing of gastric emptying.

A 13CO2 starch breath test was developed to study starch digestion in 13 healthy volunteers and 16 patients with pancreatic disease. As starch is hydrolyzed to glucose that is subsequently oxidized to CO2, the excretion of 13CO2 after starch intake, compared with the excretion of 13CO2 after glucose intake, should be a measure of starch hydrolysis. In normal subjects both the hourly 13CO2 excretion rate and the cumulative percentage of 13CO2 excretion after starch ingestion were significantly different from those after glucose ingestion. Comparable differences were found with the patient group. In addition, the 13CO2 excretion after starch intake in normal subjects was markedly different from that of patients with pancreatic disease. Even after correction for endocrine pancreatic insufficiency by calculating the ratio of 13CO2 excretion after starch intake over 13CO2 excretion after glucose intake, the difference between the control group and the patient group was statistically significant. This study indicates that starch hydrolysis is the rate-limiting step in starch digestion. It also confirms recent findings suggesting that starch digestion is impaired in some patients with pancreatic disease. The 13CO2 starch breath test may prove to be useful in evaluating the digestibility of various starch preparations in physiologic and pathological conditions.

The effect of the metenkephalin analogue Hoe 825 on esophageal motility, fundic accommodation to distention, and migrating myoelectric complex was studied in 17 healthy volunteers. The metenkephalin analogue (40 micrograms i.v.) significantly increased the duration, amplitude, and propagation velocity of the postdeglutitive esophageal peristaltic contraction waves. It had no effect on the basal lower esophageal sphincter pressure but significantly decreased the completeness of the sphincteric relaxation from 85% +/- 5% on placebo to 70% +/- 7% (p less than 0.01). The metenkephalin analogue (40 micrograms i.v.) significantly decreased the fundic accommodation to distention. In doses ranging from 20 to 60 micrograms i.v. it induced a premature phase III of the migrating motor complex that started ectopically in the duodenum (without a gastric component) and migrated distally at a significantly higher velocity than a spontaneous phase III. It is hypothesized that the metenkephalin analogue induces these effects via an inhibition of the inhibitory nervous system.

Efficacy and tissue effects of injection therapy for nonvariceal upper gastrointestinal bleeding were studied in 16 mongrel dogs. The results were compared with those obtained by neodymium-yttrium-aluminum-garnet laser, bipolar electrocoagulation, and heater probe. Epinephrine (1:10,000), absolute ethanol, and 1% polidocanol were used as injection solutions. In acute, severely bleeding experimental ulcers as well as in transected submucosal arteries, injection methods were not as effective as thermal methods in achieving complete hemostasis, although injection therapy, especially with large volumes of epinephrine (1:10,000), very quickly decreased the rate of bleeding. Chronic experiments showed that epinephrine (1:10,000) caused almost no tissue injury, but also did not induce vessel thrombosis. In contrast, absolute ethanol and 1% polidocanol caused tissue necrosis, ulceration, and vessel thrombosis, the former by acute dehydration and fixation of the tissue, the latter by acute edema and subsequent inflammation and sclerosis. These data suggest that although epinephrine injection may slow or temporarily stop bleeding, this modality is not as efficacious as injection with 1% polidocanol or absolute ethanol in inducing definitive vessel thrombosis. In the present experimental conditions sclerotherapy was not as effective as thermal methods in achieving hemostasis. These data also show that injection therapy with 1% polidocanol and absolute ethanol is by no means safer than thermal methods.

The importance of the continuity of the muscle coat and of the presence of an intraluminal bolus for the peristaltic performance of the Rhesus monkey esophagus was studied. Transection and reanastomosis with muscle-to-muscle contact in the striated muscle part of the esophagus did not interfere with the progression of primary peristaltic contractions. However, when the transection with reanastomosis was performed in the smooth muscle part of the gullet the peristaltic progression of the deglutitive contraction waves in the segment below the transection was affected. After deviation of the swallowed bolus either in the cervical striated esophagus or in the smooth muscle part of the thoracic esophagus, primary peristaltic contractions were seen to progress over the entire length of the gullet; however, in the thoracic esophagus the presence of a bolus facilitated the peristaltic progression of primary waves. These studies also indicate that the extramural vagal innervation is involved in secondary peristaltic contractions of the smooth muscle esophagus.

Bile acid output in the duodenum was studied in relation to the interdigestive migrating motor complex in normal subjects and in cholecystectomy patients. In normal volunteers the bile acid output preceding a duodenal activity front (217 +/- 89 mumol/30 min) was 374% of the output following a front (58 +/- 24 mumol/30 min) (P < 0.05). In cholecystectomy patients the prefront output (354 +/- 64 mumol/30 min) was 195% of the value obtained in the postfront period (234 +/- 59 mumol/30 min) (P < 0.05). These results indicate that the bile acid output into the duodenum during the interdigestive phase in fluctuating in accordance with the interdigestive motility complex.

The clinical, radiological, and endoscopic aspects of Yersinia enterocolitica infections in man were studied in a group of 37 adult patients observed in a 4-year period in a single gastrointestinal unit. The diagnosis was based on isolation of the bacterium in all but 1 patient. Abdominal pain and diarrhea were the most prominent symptoms, occurring in 80% of the patients. A syndrome simulating appendicitis was observed in 40%. The duration of symptoms before diagnosis varied from 1 or 2 weeks in 32 patients to several months in 5. On radiological examination the terminal ileum was involved over a distance of 10 to 20 cm in 21 of 24 patients. A coarse, irregular, or nodular mucosal pattern and pictures suggestive of ulcerations were the most prominent and early radiological signs. Endoscopic observations in 13 patients with marked diarrhea showed signs of colitis in 6 and aphthoid ulcers in 2 patients. On pathological examination, ulcerations and a nonspecific acute inflammatory cell infiltrate were observed. Although treatment with tetracycline or chloramphenicol resulted in 4 to 6 weeks in the disappearance of most symptoms and signs, pictures of "follicular ileitis" persisted for several months.