Urinary trypsinogen activation peptide (TAP) predicts severity in patients with acute pancreatitis.

CONCLUSIONS: Urinary TAP obtained within the first 48 h of the onset of symptoms can distinguish patients with severe acute pancreatitis. BACKGROUND: Urinary trypsinogen activation peptide (TAP) has recently been described as an early marker of severity in acute pancreatitis. METHODS: In a multicenter study, urine samples were collected for TAP concentration at 6-12, 24, and 48 h after admission from 139 patients with acute pancreatitis (99 with mild disease, 40 with severe disease) and from 50 control patients. Severity of acute pancreatitis was defined by the presence of organ failure and/ or pancreatic necrosis on dynamic contrast-enhanced computed tomography. RESULTS: Median urinary TAP in the 139 patients with acute pancreatitis compared to the 50 control patients was significantly higher at admission, 4.6 vs 0.8 ng/mL (p < 0.001), and 6-12 h, 1.9 vs 0.55 ng/mL (p = 0.04). Among patients who presented within 48 h of the onset of symptoms, the median urinary TAP for severe pancreatitis (9 patients) compared to mild pancreatitis (40 patients) was significantly higher at admission, 29.6 vs. 3.6 ng/mL (p = 0.001). Also, when obtained within 48 h of the onset of symptoms, all patients with severe pancreatitis had an admission urinary TAP level > 10 ng/mL. The sensitivity and specificity of an admission urinary TAP > or = 10 for severe pancreatitis was 100 and 85%, respectively. Given a cutoff of 10 ng/mL for an admission urinary TAP obtained within 48 h of the onset of symptoms, the negative predictive value was 100% for mild pancreatitis.

Comparison of once-daily doses of omeprazole (40 and 20 mg) and placebo in the treatment of benign gastric ulcer: a multicenter, randomized, double-blind study.

OBJECTIVE: The purpose of this multicenter, randomized, double-blind study, conducted in 520 patients, was to compare the efficacy and safety of omeprazole (40 and 20 mg once daily) with placebo in the treatment of benign gastric ulcer. METHODS: Treatment with omeprazole or placebo lasted 4 wk; those whose ulcers remained unhealed continued the same treatment regimen for an additional 4 wk. The effects of therapy were determined by endoscopy and assessment of GI symptoms. Safety and tolerability were evaluated through reported adverse events, physical examinations, and laboratory tests. RESULTS: At weeks 4 and 8, the proportion of patients with healed ulcers was significantly greater in the omeprazole 40- and 20-mg groups than in the placebo group (p < 0.01). At week 8, the healing rate was significantly greater in the 40-mg group than in the 20-mg group (82.7 vs 74.8%, p < 0.05). In patients with large ulcers (>1 cm), the 40-mg regimen was associated with a significantly higher healing rate (78.9%) than both the 20-mg regimen (61.4%) and placebo (34.6%) at week 8 (p < 0.05 vs omeprazole 20 mg; p < 0.01 vs placebo). Healing rates in patients with small ulcers were similar for the 40- and 20-mg groups. Omeprazole was well tolerated, with no significant differences versus placebo in the overall incidence of clinical or laboratory adverse events. CONCLUSIONS: Omeprazole 40 and 20 mg, administered once daily, healed a significantly greater proportion of patients than did placebo. The 40-mg regimen offered significant advantages over the 20-mg regimen in patients with large ulcers.

Effect of single and repeated doses of metoclopramide on the mechanisms of gastroesophageal reflux.

Decreased lower esophageal sphincter pressure, transient relaxations of the lower esophageal sphincter, and acute increases in intra-abdominal pressure are among the most common pathogenic factors in gastroesophageal reflux. This study examines the effect of metoclopramide on these factors in patients with gastroesophageal reflux disease. Six patients with clinical and endoscopic evidence of esophagitis underwent esophageal manometry and intraesophageal pH monitoring over a 5-h period (1 h basal, and 4 h postprandially). The study was done on three different days: on day 1, after placebo, on day 2, after 10 mg po metoclopramide (order randomized), and on day 3, after metoclopramide 10 mg po quid for 7 days. Metoclopramide given for 1 wk significantly increased the basal lower esophageal sphincter pressure as compared to placebo and a single dose (p < 0.05). It also significantly decreased reflux episodes during the 3rd and 4th hour postprandially when given both as a single dose or after 1 wk of treatment. There was no significant difference in the other parameters measured. Repeated metoclopramide doses decrease reflux episodes in patients with reflux esophagitis by increasing basal lower esophageal sphincter pressure and possibly by accelerating gastric emptying.

Bismuth subsalicylate suppression of Helicobacter pylori in nonulcer dyspepsia: a double-blind placebo-controlled trial.

Gastritis caused by Helicobacter pylori (HP) is common in patients with nonulcer dyspepsia (NUD), but an etiologic relationship between the histologic lesion and clinical symptoms is unproven. HP is inhibited by bismuth subsalicylate (BSS), a traditional remedy for dyspeptic complaints. The aim of this study was to assess the short- and long-term effects of BSS on HP, gastritis, and symptoms in patients with NUD. One hundred twenty-six patients with NUD who were shown to be infected with H. pylori (HP+) were enrolled. There was a two-week placebo run-in period to eliminate placebo responders. Fifty patients remained symptomatic and were randomly assigned to therapy with either BSS liquid or a matching placebo. EGD, biopsy, and clinical evaluations were performed at entry, at week 5 (end of therapy), at week 9 (four weeks after therapy), or at time of symptomatic relapse. Twenty-seven patients received placebo and 23 patients received BSS. BSS suppressed H. pylori in 15/23 patients (65%) and eradicated it in one patient, whereas the placebo had no effect on H. pylori. Gastritis improved during therapy with BSS but relapsed by week 9. There was no significant change in level of dyspeptic symptoms during or after treatment, although one month after the end of treatment, the patients in the BSS group consistently had lower symptom scores and fewer symptomatic days for all symptoms measured. The study confirms that BSS given for three weeks suppresses but does not usually eradicate H. pylori. Such short-term suppression of H. pylori heals gastritis but does not result in clinical improvement.

Intestinal perforation due to Mycobacterium tuberculosis in HIV-infected individuals: report of two cases.

Intestinal perforation is an extremely uncommon complication of Mycobacterium tuberculosis (MTB) infection. We describe two cases of multiple intestinal perforations secondary to MTB in individuals infected with the human immunodeficiency virus (HIV) presenting at the Los Angeles County-University of Southern California Medical Center over a 2-month period. For each case, this was the first presentation of AIDS. One of the two patients had concurrent pulmonary involvement. One patient died, and the other responded to therapy and was discharged in stable condition. The most striking finding in both cases was the extremely large number of acid-fast bacteria seen transmurally on the pathological specimens. This might be related to impaired T-cell function. The resurgence of MTB infection in North America, in the presence of the AIDS epidemic, may result in an increasing frequency of unusual presentations, such as intestinal perforation. Intestinal perforation due to MTB should be considered in HIV-infected patients presenting with an acute abdomen.

Pancreatic secretion in chronic alcoholics. Effects of acute alcohol or wine on response to a meal.

To gain further insight on the effects of alcohol on human pancreatic enzyme secretion, we tested the effects of a 12% (v/v) alcohol solution, wine, and a glucose solution added to a meal on trypsin output in duodenal aspirate of nonalcoholic volunteers and compared the results to those of chronic alcoholics. Plasma concentrations of gastrin, cholecystokinin, and pancreatic polypeptide were monitored pre- and postprandially. Similar blood alcohol concentrations were determined in nonalcoholics and alcoholics following wine and the alcohol solution. Nonstimulated trypsin output (basal) was higher in alcoholics but not significantly so when compared to nonalcoholics. However postprandial trypsin output, 2014 +/- 301 mg/5 hr was significantly greater in alcoholics (P < 0.05) compared to nonalcoholics 1271 +/- 118 mg/5 hr. Alcohol and wine when added to the meal significantly (P < 0.05) inhibited trypsin output in both groups. Basal and postprandial levels of gastrin and cholecystokinin were similar in nonalcoholics and alcoholics. Basal plasma pancreatic polypeptide levels were similar in both groups, but the postprandial increments in pancreatic polypeptide levels observed in nonalcoholics were not observed in alcoholics. We conclude that chronic alcoholics have increased postprandial pancreatic enzyme secretion, and that this secretion, as that of nonalcoholics, can be affected by alcohol or wine. The postprandial hypersecretion of enzymes in alcoholics is not related to increased plasma levels of cholecystokinin or gastrin. It is possible that the impaired release of pancreatic polypeptide may participate in the mechanism for increased pancreatic enzyme secretion in chronic alcoholics.

Dysphagia. A practical approach to diagnosis.

Our diagnostic approach to a patient with dysphagia begins with detailed history taking and physical examination. On the basis of findings, a radiographic and/or endoscopic study of the esophagus is done. We usually have barium-swallow radiography done initially, and if the radiographs are equivocal, upper gastrointestinal endoscopy is performed. Manometric studies are reserved for patients with suspected motility disorders.

Chronic alcohol consumption intensifies caerulein-induced acute pancreatitis in the rat.

Rats were chronically fed either an ethanol-containing diet (36% of total calories derived from alcohol) or a pair-fed, control diet (no alcohol) for 8 wk, and acute pancreatitis (AP) was subsequently induced by a 3-h i.v. infusion of caerulein (CR) at a dose of 5 micrograms/kg/hr. CR-induced AP in control rats (no alcohol) was characterized by a significant elevation in serum lipase content, pancreatic interstitial edema, infrequent occurrences of karyorrhexis, and the appearance of vacuoles in acinar cells. Chronic feeding of the ethanol diet followed by treatment with CR resulted in increases in serum lipase content, interstitial edema, karyorrhexis, and acinar vacuolization that were significantly greater than that seen in rats fed the control diet and treated with CR. It is concluded that chronic ethanol intake in the rat intensifies AP that is subsequently induced by CR.

Variability of migrating motor complex in humans.

Fasting gastrointestinal motility in the human is characterized by the regular cycling activity of the migrating motor complex (MMC). Our purpose was to define the variability of the MMC within and between a group of six healthy subjects studied for 6-9 hr over six separate days with a perfused catheter system. A total of 88 phase III events was observed during 255 hr of recording in this group. The mean MMC cycling time varied significantly between subjects (range 113-230 min, P less than 0.001), and variation within subjects also was wide (SD range 58-70 min). Seventy-one percent of phase III events commenced in the gastric antrum, 18% in the proximal duodenum, 10% in the distal duodenum, and 1% in the proximal jejunum. For each subject, the velocity of propagation of phase III decreased significantly (P less than 0.001), and phase III duration increased significantly (P less than 0.001), with increasing distance from the os. In the antrum, phase I was predominant, and significant (P less than 0.006) variation between subjects was noted for percentage of MMC cycle occupied by phase I (overall mean +/- SD 55 +/- 23%). Phase II was predominant in both duodenum and jejunum (mean range 70-80%), and no significant variation was noted between subjects for percentage of MMC occupied by phase II. We conclude that human MMC activity varies widely between individuals and within the same individual when studied on separate days.

Role of fasting gastrointestinal motility in the variability of gastrointestinal transit time assessed by hydrogen breath test.

Gastrointestinal motility and transit time, measured by the hydrogen breath test, were simultaneously assessed in six healthy volunteers. Each subject underwent six studies on separate days. On each day motility was measured in the gastric antrum, duodenum, and proximal jejunum and 15 g of lactulose was given either by mouth during gastric phases I, II, III of the motor migrating complex or infused duodenally during duodenal phases I, II, III, one phase being studied each day in random order. Fasting activity was not interrupted by the lactulose. The lactulose transit time decreased significantly from a peak with phase I through phase II to a minimum with phase III (mean (SD) 155 (26) min v 120 (10) min v 94 (14) min, p less than 0.001). Similar results were noted when the lactulose was instilled intraduodenally (156 (23) min v 125 (19) min v 100 (17) min, p less than 0.001). No correlation was found between motility index and transit. These results suggest that different phases of fasting gastrointestinal motility are major determinants of the transit time estimated by the hydrogen breath test and explain the variability of this test in practice.

U.S. experience with omeprazole in duodenal ulcer. Multicenter double-blind comparative study with ranitidine. The Omeprazole DU Comparative Study Group.

To assess the comparative efficacy of omeprazole 20 mg, a proton pump inhibitor, versus ranitidine 150 mg twice a day, an H2-receptor antagonist, in healing duodenal ulcers we performed a randomized, double-blind, multicenter trial in 309 patients with endoscopically diagnosed ulcers. Patients were treated for up to four weeks and were seen at week 2 and at week 4, if unhealed at week 2, for determination of ulcer status by endoscopy, review of daily self-assessment symptom diaries, and clinical laboratory including fasting serum gastrin. Gastrin levels were repeated two weeks after cessation of study medication. Evaluation of baseline demographic and laboratory parameters demonstrated no significant differences between the two groups at entry. At week 2, 42% of the omeprazole and 34% of the ranitidine-treated patients were healed (P = NS). At week 4, there was a 19% advantage in ulcer healing for the omeprazole-treated patients in comparison to those treated with ranitidine (82% vs 63%, respectively, P less than 0.05). Healing of ulcers greater than or equal to 1.0 cm occurred in 83% of those treated with omeprazole versus 37% treated with ranitidine (P less than 0.01). There were no significant differences in rate of pain relief or incidence of clinical laboratory abnormalities. Mean fasting serum gastrin value during treatment increased over the baseline in both groups, (P less than 0.05). The percent change was significantly greater with omeprazole but few patients had elevations above the upper limit of normal for the assay. Both drugs were well tolerated. Omeprazole 20 mg demonstrated superiority in healing duodenal ulcers at four weeks in comparison to ranitidine 150 mg twice daily and was more effective in healing ulcers greater than or equal to 1.0 cm.

Changes in the relative frequency of gastric adenocarcinoma in southern California.

The incidence of gastric cancer is decreasing in most counties of the developed world, but at the Los Angeles County-University of Southern California Medical Center, we diagnosed 99.8 cases of gastric adenocarcinoma per 10(5) discharges in the period 1982 to 1986 as opposed to 62.2 per 10(5) discharges in 1972 to 1976 (P less than .0001). This change involved primarily Hispanics younger than 30 years of age with 30 cases per 10(5) vs 4.2 cases per 10(5) (P less than .0001) and whites older than 30 years: 87 cases per 10(5) vs 54 cases per 10(5) (P less than .05) during 1982 to 1986 and 1972 to 1976, respectively. There was no change in the relative frequency rates of gastric adenocarcinoma among African Americans and Asians. Although these changes do not seem important enough to make the detection of gastric cancer a high-priority public health problem, they should alert physicians working in areas with high Hispanic populations of the relative possibility of the occurrence of gastric malignancy even in young patients. Also, we have found that gastric cancer is still prevalent in whites of low socioeconomic class.

Effect of bolus volume on the response of the human esophagus to a viscous bolus.

It is well known that increasing the volume of a non-viscous bolus has no significant effect on esophageal peristalsis. Viscous boluses, however, tend to remain more compact during passage through the esophagus; we therefore sought to determine whether increasing the volume of a viscous bolus would significantly affect esophageal peristalsis. Intraluminal pressure events were measured with a low-compliance-infused catheter system, and lower esophageal sphincter (LES) pressure was monitored continuously with a Dent sleeve. Each subject was given a series of 10 swallows of a water bolus (viscosity, 0.89 centipoise) and of a viscous bolus (syrup; viscosity, 102 centipoise). The volume of each bolus varied (5, 10, 15, 20 ml), and the order of administration of each set of swallows was randomized. Tracings were coded and analyzed blindly. Increasing the volume of the non-viscous bolus had no significant effects of esophageal peristalsis. Additionally, the viscous bolus at each volume was associated with significant (p less than 0.05) reductions in peristaltic wave velocity and significant (p less than 0.05) increments in durations of contraction and LES relaxation. However, increasing the volume of the viscous bolus did not significantly alter variables of esophageal peristalsis. It is concluded that altering the volume of a viscous bolus has no incremental effect on esophageal peristalsis over the effect of viscosity alone.

Esophageal function in humans. Effects of bolus consistency and temperature.

We determined the effect of increased bolus consistency on esophageal motor function in 11 healthy volunteer subjects. Further, we sought to define the esophageal response to boluses with a wide range of temperatures in nine healthy volunteers. Intraluminal pressure events were measured with an infused catheter system, and lower esophageal sphincter pressure was monitored continuously with a Dent sleeve. Boluses (10 swallows each) consisting of 5 ml of a solid suspension (yogurt), 5 cm3 of a soft solid (gelatin), and 5 ml of water were given in a randomized order. In a separate study, boluses with temperatures of 1 degree C, 5 degrees C, 10 degrees C, 15 degrees C, room temperature, 30 degrees C, 40 degrees C, 50 degrees C, and 60 degrees C were given in a randomized fashion. Compared to the water bolus, the solid boluses elicited a significant (P less than 0.05) reduction in peristaltic wave velocity, which was accompanied by significant (P less than 0.05) increments in the durations of wave contraction and lower esophageal sphincter relaxation. The magnitude of the response elicited by the solid boluses was comparable to that noted with boluses of high viscosity suggesting that the esophagus response to increments in bolus viscosity and consistency in a similar fashion. Alterations in bolus temperature did not elicit any significant changes in the parameters of esophageal peristalsis. It is concluded that bolus temperature does not have a significant role in the modulation of human esophageal peristalsis except under conditions that cause a change in esophageal wall temperature.

Effect of alcohol and alcoholic beverages on meal-stimulated pancreatic secretion in humans.

Alcohol and alcoholic beverages may have different effects on pancreatic secretion and hormone release in humans. To test this hypothesis we studied the effects of an alcohol solution and a glucose solution and compared them with those of alcoholic beverages on postprandial pancreatic secretion and release of gastrin, trypsin, and cholecystokinin in 6 healthy nonalcoholic male volunteers. Pancreatic enzyme secretion was measured in duodenal aspirate, plasma trypsin, and gastrin by radioimmunoassay and cholecystokinin by bioassay. The meal plus glucose significantly stimulated pancreatic enzyme secretion, release of gastrin and cholecystokinin, and caused no changes in plasma trypsin. The alcohol solution and all beverages added to the meal caused similar increases in alcohol blood levels and significantly less pancreatic enzyme secretion compared with the meal plus glucose. Plasma trypsin levels remained unchanged. Compared with the meal plus glucose, wine and beer caused a significantly higher release of gastrin, and beer also released significantly more cholecystokinin. Inhibition of pancreatic enzyme secretion stimulated by a meal in nonalcoholics is a common effect of alcohol and alcoholic beverages despite some differences on release of gastrointestinal peptides. This effect may have some implications in the pathogenesis of alcoholic pancreatitis.

A multicenter, randomized, double-blind trial of somatostatin in the management of acute hemorrhage from esophageal varices.

A prospective, randomized, placebo-controlled, double-blind, multicenter clinical trial of intravenous somatostatin (Stilamin; Serono Laboratories, Inc., Randolph, MA) was performed in 102 patients with actively bleeding esophageal varices from August, 1985, to November, 1986. Patients had major hemorrhage indicated by hematemesis or melena and evidence of significant blood loss. For entry, patients had to have endoscopic demonstration of active bleeding from esophageal varices or stigmata of recent hemorrhage and bright red blood in the gastric aspirate with no other source of bleeding found. Randomized patients received identical-appearing somatostatin or placebo for a 30-hr study period. Those given somatostatin received a 250-micrograms bolus and a 250-micrograms per hr infusion with repeat bolus and doubling of the infusion if the bleeding was not controlled. In retrospect, 18 patients could not be evaluated. Of the 84 evaluable patients, 48 received somatostatin and 36 placebo. They were comparable in age, gender, severity of liver disease and history of variceal bleeding. Transfusion requirements were similar in both groups. Bleeding stopped for 12 consecutive hr during 30 hr of the study period in 31 (65%) of the somatostatin group vs. 30 (83%) of the placebo group (p = 0.06). The median time to cessation of bleeding was 2 hr in the placebo group and 3 hr in the somatostatin group. Deaths following the study period were nine (25%) in the placebo group and 15 (31%) in the somatostatin group. Within the limitations of the present study, we conclude that somatostatin was ineffective in the management of active bleeding of esophageal varices.

Modulation of esophageal peristalsis by alterations of body position. Effect of bolus viscosity.

Previous studies have demonstrated that nonviscous liquids traverse the esophagus more rapidly with the subject in the upright rather than the supine position. Conversely, similar studies have shown that viscous liquids traverse the esophagus at similar rates for both upright and supine positions. Our purpose was to define the motor correlates of these differing responses. Six normal volunteers were studied with an infused catheter system incorporating a Dent sleeve for monitoring lower esophageal sphincter pressure. The subjects were given a series of swallows of a water and a viscous (52 centipoise) bolus in both the supine and upright positions. In the upright position, the water bolus caused an increased velocity of propagation in the proximal esophageal segment that was associated with a shortening of lower esophageal sphincter relaxation time and reductions in amplitude and duration of contraction. No significant changes in the peristaltic wave were noted with the viscous bolus during alterations of body position. We conclude that the more rapid transit of a nonviscous water bolus through the esophagus in the upright position is reflected in specific alterations of esophageal peristaltic parameters. The possible mechanisms for these differing responses are discussed.

Response of lower esophageal sphincter to alterations of intraabdominal pressure.

It is well documented that lower esophageal sphincter pressure increases significantly in response to increases in intraabdominal pressure in order to maintain the gastroesophageal barrier. The mechanism by which this response is elicited is controversial. It has been suggested that the response of the sphincter persists after the intraabdominal pressure stimulus is removed. The present study sought to define the response of the sphincter to increased intraabdominal pressure (achieved by straight leg raising) by continuously monitoring it with the Dent sleeve in a group of 10 normal volunteers. A reproducible pressure profile was observed in both the sphincter and the stomach, characterized by an initial peak, a sustained plateau, and a second peak. The pressure profiles of the stomach and the sphincter were closely approximated and peak and plateau pressures for both did not differ significantly. The onset and offset of the pressure increase were simultaneous in the stomach and the sphincter. No significant changes in sphincter pressure were noted when the rapid pull-through technique was used. This study defines the pressure profiles of the stomach and the lower esophageal sphincter zone during increased intraabdominal pressure in man. Our data suggest that the response of the sphincter is passively mediated.

Cisapride stimulates antral motility and decreases biliary reflux in patients with severe dyspepsia.

Duodenogastric reflux has a deleterious effect on the gastric mucosa. It was the aim of this study to assess the acute effects of cisapride on antroduodenal motility and duodenogastric reflux in seven patients with severe dyspepsia and increased biliary reflux, as evidenced by increased bile salt output in their gastric aspirates. Each patient underwent two studies on separate days. On each day, after an overnight fast, each patient swallowed a multilumen tube for manometric recording of gastroduodenal motility. Phenol red was infused into the second portion of the duodenum, gastric juice was aspirated, and motor activity was monitored for 90 min. At the end of this period, the patient received either cisapride or placebo intravenously in a double-blind randomized fashion. Antroduodenal motility and duodenogastric reflux were monitored for the subsequent 90 min. A significantly (P less than 0.01) higher motility index was found in the antrum after cisapride (2678 +/- 712 vs 1110 +/- 412 in the basal period) while placebo had no effect. The duodenal motility index was not affected by cisapride or placebo. Bile salt outputs in gastric aspirates were significantly (P less than 0.05) reduced following cisapride injection (0.42 +/- 0.6 mmol vs 1.6 +/- 1.2 mmol during basal period). Conversely, outputs of phenol red in the gastric aspirates were unaffected by cisapride. In conclusion, cisapride stimulates antral motility and decreases biliary reflux in patients with dyspepsia and increased duodenogastric reflux.

Effect of bolus osmolality on human esophageal function.

The effect of bolus osmolality on human esophageal function is undefined. We sought to define the response of the human esophagus to boluses with a wide range of osmolalities in 10 healthy male volunteers. Intraluminal pressure events were measured with an infused catheter system, and lower esophageal sphincter pressure was monitored continuously with a Dent sleeve. Each subject was given a series of 10 swallows of each of seven boluses, which consisted of water, mannitol solutions with osmolalities of 142, 296, 449, 704, and 1481 mOsm/kg, and orange juice (585 mOsm/kg), in a randomized fashion. Tracings were coded and analyzed blindly. Alterations in bolus osmolality did not elicit any significant changes in amplitude and duration of contraction, velocity of wave propagation, or the duration of relaxation of the lower esophageal sphincter. We conclude that bolus osmolality does not play a significant role in the control of human esophageal motility, and that this lack of effect is explained by consideration of esophageal muscle mechanics.