A patient with gastric outlet syndrome (Bouveret's syndrome) caused by a large gallstone impacted in the duodenal bulb was successfully treated by extracorporeal shock-wave lithotripsy. Thus, open abdominal surgery could be avoided. For disintegration of the stone, three consecutive lithotripsy procedures were necessary. Thereafter, stone fragments could be extracted endoscopically. Extracorporeal shock-wave lithotripsy could become a non-surgical alternative in patients with obstruction of the duodenum caused by a gallstone.

In this study the interaction of gallbladder mucin subunits was examined by gel permeation chromatography, quasielastic laser light scattering, and viscometry. Purified mucin eluted primarily in the void volume of a Sepharose 2B-Cl column, indicating a molecular weight above 2 x 10(6). Disaggregation of the mucin polymer resulted in the elution of glycoprotein in the included volume of the Sepharose 2B-Cl column. Gallbladder mucin had a hydrodynamic radius of 630 A that was independent of mucin concentration below 2 mg/ml. At mucin concentrations above 2 mg/ml, a concentration-dependent increase in both hydrodynamic radius and apparent viscosity of gallbladder mucin was observed. Mucin demonstrated a strong pH dependence in hydrodynamic radius and viscosity with the maximum occurring at approximately pH 5.5. These findings suggest that noncovalent interactions participate in bovine gallbladder mucin subunit associations. Furthermore, changes that occur in the physicochemical environment of the gallbladder during periods of stasis may enhance the viscoelastic properties of mucin and promote the accumulation of biliary sludge in the gallbladder.

The nature of gastric infiltrates consisting primarily of benign-appearing small lymphocytes is at present a controversial issue. Earlier reports of gastric lymphoma developing in gastric pseudolymphoma and more recent immunohistochemical studies demonstrating monoclonal B-cell populations in pseudolymphoma suggest that at least some cases represent low-grade lymphomas or clonal precursor lesions that may develop into lymphoma. Observations of a small lymphocytic infiltrate arising in the region of a gastric ulcer that lacked definitive morphologic evidence of malignancy (lymphoma) but was clearly a monoclonal B-cell proliferation by immunohistochemical and gene rearrangement studies support the notion that some gastric lymphoproliferative lesions that histologically have been called pseudolymphomas may include one or more clonal lymphoid expansions. A histopathologic/molecular model suggesting a potential pathway for the development of morphologically recognizable lymphoma from benign-appearing small lymphocytic infiltrates is presented, and the concept that for a variety of lymphoid proliferations clonality and malignancy may not be synonymous is discussed.

The ability of hypnosis to both stimulate and inhibit gastric acid secretion in highly hypnotizable healthy volunteers was examined in two studies. In the first, after basal acid secretion was measured, subjects were hypnotized and instructed to imagine all aspects of eating a series of delicious meals. Acid output rose from a basal mean of 3.60 +/- 0.48 to a mean of 6.80 +/- 0.02 mmol H+/h with hypnosis, an increase of 89% (p = 0.0007). In a second study, subjects underwent two sessions of gastric analysis in random order, once with no hypnosis and once under a hypnotic instruction to experience deep relaxation and remove their thoughts from hunger. When compared to the no-hypnosis session, with hypnosis there was a 39% reduction in basal acid output (4.29 +/- 0.93 vs. 2.60 +/- 0.44 mmol H+/h, p less than 0.05) and an 11% reduction in pentagastrin-stimulated peak acid output (28.69 +/- 2.34 vs. 25.43 +/- 2.98 mmol H+/h, p less than 0.05). We have shown that different cognitive states induced by hypnosis can promote or inhibit gastric acid production, processes clearly controlled by the central nervous system. Hypnosis offers promise as a safe and simple method for studying the mechanisms of such central control.

We have investigated a negative feedback mechanism in the intestinal phase of pancreatic exocrine secretion in dogs with gastric cannulas and Thomas duodenal cannulas in whom pancreatic juice was collected by cannulation of the main pancreatic duct. Intraduodenal infusion of oleic acid emulsion in a dose of 18 mmol/h resulted in a significant increase in pancreatic secretion of water, bicarbonate, and protein, which was accompanied by increased plasma concentrations of both secretin and cholecystokinin. Infusion of pancreatic juice or bovine trypsin into the duodenum significantly inhibited the oleic acid-stimulated pancreatic secretion. This inhibition coincided with a significant decrease in plasma secretin level, whereas plasma cholecystokinin concentration was not affected by either pancreatic juice or trypsin. Neither pancreatic secretion nor plasma secretin concentration was affected by intraduodenal administration of NaHCO3 solution. The trypsin-induced suppression of pancreatic secretion was prevented by intravenous administration of secretin in a dose that achieved a plasma secretin level comparable to that during the oleic acid administration. This study indicates that a negative feedback mechanism is operative in the intestinal phase of pancreatic exocrine secretion in dogs, and endogenous secretin plays a significant role in the mechanism.

Studies were performed to determine the mechanism by which short-chain fatty acids increase colonic Na and Cl absorption by determining unidirectional 22Na and 36Cl fluxes across isolated stripped mucosa from the rat distal colon under voltage clamp conditions. Mucosal butyrate (25 mM, in the absence of bicarbonate) significantly enhanced both net Na and net Cl absorption by 7.0 +/- 1.3 and 6.9 +/- 1.0 microEq/h.cm2, respectively, without increasing the short-circuit current. Net Na and Cl absorption in butyrate-Ringer's solution and HCO3-Ringer's solution were identical. Butyrate stimulation of Na (and Cl) absorption was Cl-dependent and prevented by 1 mM mucosal amiloride, an inhibitor of Na-H exchange, but was HCO3-independent and not inhibited by acetazolamide, a carbonic anhydrase inhibitor. In contrast, bicarbonate-stimulated Na (and Cl) absorption was also Cl-dependent and amiloride-sensitive, but was significantly inhibited by acetazolamide. The effect of mucosal butyrate on net Na and Cl absorption was substantially greater than serosal butyrate, which in the presence of bicarbonate did not alter ion transport. The stimulation of Na and Cl absorption by mucosal butyrate was significantly greater than by propionate and acetate, whereas mucosal formate did not alter Na transport. The results of this study permit the following model: short-chain fatty acid stimulation of active Na and Cl absorption involves uptake of the nonionized form of butyrate and the coupling of Na-H and Cl-butyrate exchanges.

We investigated a possible role of secretin in the mechanism of exocrine pancreatic secretion after exclusion of pancreatic juice from the intestine in anesthetized rats. Diversion of pancreatic juice from the duodenum resulted in a significant increase in plasma secretin concentration from 0.76 +/- 0.39 pM at 0 time to 3.09 +/- 0.30 pM at 4 h after diversion. This increase in secretin coincided with a steady but significant increase in pancreatic secretion of volume and bicarbonate. Intraduodenal administration of fresh pancreatic juice completely reversed the diversion-induced increases in both plasma secretin and pancreatic secretion. Intravenous injection of a rabbit-antisecretin serum blocked the increase of pancreatic secretion during diversion of pancreatic juice from the duodenum. Thus, we conclude that endogenous secretin is involved in a hormonal mechanism regulating increased pancreatic exocrine secretion in pancreatic juice-diverted rats.

Amoxicillin-clavulanate potassium, a semisynthetic penicillin-beta-lactamase inhibitor combination drug, is a widely used oral antibiotic. Since the marketing of this drug in 1984, more than nine million prescriptions have been dispensed. Several cases of jaundice and hepatic dysfunction have been observed and reported to the Food and Drug Administration and the pharmaceutical company (Beecham Laboratories). A review of 18 of these cases revealed a predominantly cholestatic syndrome in 7 cases, a mixed hepatocellular-cholestatic picture in 6 cases, a hepatocellular pattern in 4, and in 1 case the injury could not be clearly defined. No fatalities were observed, and all cases had reversal of hepatic dysfunction upon cessation of the drug. Fever was present in 2 patients and eosinophilia in 6 of 10 patients tested, suggesting a hypersensitivity phenomenon contributing to hepatic dysfunction in some of the cases. A percutaneous liver biopsy had been performed in 7 of 18 patients and four of these were reviewed by the authors. Prominent centrizonal cholestasis was seen in all four biopsies. Additionally, 1 patient had periportal and another had midzonal cholestasis. Although infrequent, recognition of an often benign cholestatic syndrome associated with amoxicillin-clavulanate potassium will help avoid unnecessary, invasive, and expensive diagnostic studies and also ameliorate symptoms upon withdrawal of the drug.

Electronic (video) endoscopes are a significant new development in gastroenterology, offering the potential of enhanced teaching and permanent storage of pictorial data. The primary concern of gastroenterologists is the resolution and color performance of these instruments, as these parameters have important bearings on the ability to discern pathological changes in mucosa. We sought to determine the resolution and color capabilities of electronic colonoscopes and compare them with a conventional fiber colonoscope. Resolution was determined using a standard test chart at various distances and the number of picture elements (a measure of resolution) was calculated. The mean number of picture elements was Fujinon (219), Fiber (172), Pentax (169), Toshiba (142), Olympus (140), and Welch Allyn (133). In close focus examination (target distances less than 1 cm), the Fujinon and Toshiba endoscopes had significantly higher resolution than the other instruments. Color was measured quantitatively using a standard color chart and a color analyzer. Color polygons were plotted for each endoscope on a reference chromaticity diagram. All systems had an acceptable overall performance but color was undersaturated with some systems. The optical performance of electronic endoscopes has improved considerably since the inception of electronic endoscopy.

Steatorrhea can result from maldigestion or malabsorption. As the pathophysiology underlying impaired digestion differs from impaired absorption, it is important to differentiate these two disorders. It is generally accepted that patients with maldigestion excrete an excessive amount of triglyceride and patients with malabsorption excrete an excess of the lipolytic product of triglyceride, fatty acid. The two-step Sudan stain has been used as a simple test to differentiate these disorders. The validity of the test has not yet been established. In this study, fecal fatty acid and triglyceride were measured after extraction and thin-layer chromatographic separation. Our results indicate that in adult patients with pancreatic insufficiency, the fecal triglyceride content does not differ from the controls. However, a fivefold to sixfold increase in fecal fatty acid content in patients with pancreatic insufficiency was revealed. As patients with maldigestion do not excrete an excess of undigested triglyceride, it is not possible to differentiate maldigestion from malabsorption by quantifying fecal triglyceride and fatty acid.

The development of a large animal model of fulminant hepatic failure produced with acetaminophen that should be useful in the development and evaluation of potential medical therapies for the important clinical problem of fulminant hepatic failure is described. Acetaminophen in dimethyl sulfoxide (600 mg/ml) given as three subcutaneous injections, with the first dose (750 mg/kg body wt) being given at noon, the second dose (200 mg/kg body wt) being given 9 h later, and the third dose (200 mg/kg body wt) being given 24 h after the initial dose consistently produces fulminant hepatic failure in dogs. The dimethyl sulfoxide vehicle, injected intramuscularly, does not influence either animal survival or hepatic function in control-treated dogs. No deaths occur within the first 36 h. By 72 h after initial drug administration, the mortality is 90%. Histopathological and biochemical investigations demonstrate a high degree of hepatocellular necrosis in nonsurviving animals without appreciable damage to the kidneys, lungs, or heart. The drug schedule and preparation outlined avoids the administration of large volumes of vehicle and results in prolonged high levels of acetaminophen in the blood sufficient to induce severe hepatic injury. Ranitidine (120 mg/kg body wt i.m.) given 30 min before each acetaminophen dose significantly reduces the mortality and hepatic necrosis produced using this model. This model satisfies all criteria established by Miller et al. for the production of a suitable large animal model of fulminant acute hepatic failure.

Colon motility and myoelectric slow wave activity were compared in 10 patients with progressive systemic sclerosis and 18 controls. Recordings were made in the rectosigmoid and rectum, 25-30 cm and 10-15 cm from the anal margin, respectively, during two 4-min baselines and in response to stepwise distention of the colon with an air-filled balloon. During baseline, the motility (activity index, defined as cumulated areas of all waves divided by recording time) of the rectosigmoid was similar in patients with progressive systemic sclerosis (0.38 +/- 0.61 in baseline 1, 0.86 +/- 1.33 in baseline 2) and controls (1.15 +/- 2.02 in baseline 1, 0.77 +/- 1.01 in baseline 2). Rectal motility was also similar during baseline in patients with progressive systemic sclerosis (1.43 +/- 2.56 in baseline 1, 1.65 +/- 2.47 in baseline 2) and controls (0.56 +/- 0.80 in baseline 1, 0.62 +/- 0.94 in baseline 2). Patients showed a lower tolerance for balloon distention of the colon (average, 130 vs. 184 ml) and a greater amount of contractile activity than controls after balloon distention (rectosigmoid activity index, 1.05 +/- 1.24 vs. 0.07 +/- 0.14; rectal activity index, 2.75 +/- 3.71 vs. 0.13 +/- 0.31). Maximum tolerable volume of balloon distention was inversely correlated to complaints of diarrhea in patients. Slow wave myoelectric activity did not differentiate patients from controls. These findings suggest that diarrhea, and possibly other gastrointestinal symptoms associated with progressive systemic sclerosis, may be due to decreased compliance of the bowel.

The thesis of this paper is that gastropathy associated with nonsteroidal antiinflammatory drugs (NSAIDs) is the most frequent and, in aggregate, the most severe drug side effect in the United States. This work is based on a consecutive series of 2400 patients with rheumatoid arthritis followed prospectively for an average of 3.5 yr by ARAMIS, the American Rheumatism Association Medical Information System. We present a preliminary exploration of the magnitude of the problem, the population at risk, and the patients within that population who are at particularly high risk. Patients on NSAIDs had a hazard ratio for gastrointestinal (GI) hospitalization that was 6.45 times that of patients not on NSAIDs. Characteristically, high-risk patients for GI hospitalization and GI death are older, have had previous upper abdominal pain, have previously stopped NSAIDs for GI side effects, and have previously used antacids or H2-receptor antagonists for GI side effects. They also are frequently on corticosteroids. In contrast, patients attributing relatively minor symptoms to the drug tend to be younger and more frequently female. Our preliminary analysis is univariate and, as these variables are interdependent, firm conclusions regarding the relative importance of these risk factors will require reevaluating our data base as it is expanded using multivariate analysis. The syndrome of NSAID-associated gastropathy can be estimated to account for at least 2600 deaths and 20,000 hospitalizations each year in patients with rheumatoid arthritis alone.

Two infants under 3 mo of age who presented with obstructive jaundice secondary to cholelithiasis are reported. Neither infant had any congenital anatomic abnormality of the biliary tract leading to stasis, yet both had cultures of gallbladder bile that grew abundant bacteria. In both, recovery of gallbladder bile and sludge or actual stones allowed a detailed analysis of bile and stone composition. Bile was not saturated with cholesterol. In both cases, unconjugated bilirubin accounted for a large percentage of the total bile biliary pigments measured, and stercobilin was present in gallbladder bile. Bile beta-glucuronidase activity was higher when measured at the optimal pH of bacterial rather than tissue beta-glucuronidase. Analysis of stone morphology and composition showed characteristics of brown pigment gallstones with a layered appearance and the presence of calcium palmitate. This is the first report of detailed bile and stone analysis in infants and supports the hypothesis that brown pigment gallstones form spontaneously in infants who have bacterial infections in the biliary tract.

The 1982-1984 Hispanic Health and Nutrition Examination Survey used ultrasonography to investigate the epidemiology of gallstone disease. Mexican American, Cuban American, and Puerto Rican men and women, aged 20-74 yr, were selected from household samples in Texas, New Mexico, Arizona, Colorado, California, Connecticut, New Jersey, New York, and Florida. Ultrasonography was performed on 2299 persons. The age-adjusted prevalence of gallstone disease (gallstones + cholecystectomy) among Mexican American men (7.2%) was 1.7 times that of Cuban American men and 1.8 times that of Puerto Rican men. The prevalence for Mexican American women (23.2%) was 1.5 times that of Cuban American women and 1.7 times that of Puerto Rican women. Rates were about three times higher among women than men and increased with age in both sexes and all ethnic groups except older Puerto Rican women. Among Mexican American women aged 60-74 yr, the prevalence of gallstone disease reached 44.1%. These results support the hypothesis that Mexican Americans are at increased risk of gallstone disease.

This paper describes experiments that were designed to study postuptake modification by isolated rat Kupffer cells of a 3H,14C-biosynthetically labeled endotoxin purified from Escherichia coli J5 as assessed by cesium chloride isopyknic density gradients and gel permeation chromatography. Pulse-chase experiments demonstrated that half as much of the endotoxin's lipid, relative to polysaccharide, was released by the cells. Density gradients revealed that native endotoxin equilibrated at a density of 1.412 g/ml, whereas endotoxin retained by Kupffer cells equilibrated at densities of 1.274 and 1.295 g/ml. Gel permeation chromatography indicated that endotoxin retained by Kupffer cells formed a larger micelle than either exocytosed or native endotoxin. Endotoxin exocytosed by Kupffer cells fractionated into two peaks, one with a smaller and one with a larger apparent micelle size than native endotoxin but both smaller than the retained lipopolysaccharide. Both systems indicated that the Kupffer cell modified endotoxin by enriching the lipid content of the molecule and shortening the length of the O-antigen. Thus, the Kuffer cell, in its mode of action on the endotoxin molecule, appears to play a prominent role in the initial phase of a biochemical process for endotoxin clearance and detoxification.

The purpose of this investigation was to characterize the nature of peptide histidine isoleucine (PHI) and vasoactive intestinal polypeptide (VIP) receptors, and to examine the role of PHI in internal anal sphincter (IAS) relaxation. The studies were performed on opossums anesthetized with alpha-chloralose. The pressures in the IAS were recorded using continuously perfused catheters. The IAS responses to PHI analogues, PHI-27, PHM-27, PHI-(14-27)-NH2, PHI-(1-13), to VIP, to rectal balloon distention, sacral nerve stimulation, and local intramural stimulation were evaluated before and after PHI-(14-27)-NH2, PHI tachyphylaxis, and the VIP antagonists [4 Cl-D-Phe6, Leu17] VIP (VIP analogue) and (N-Ac-Tyr1, D-Phe2)-GRF(1-29)-NH2 (growth hormone releasing factor analogue). The inhibitory responses by all of the PHI analogues and VIP were not modified by tetrodotoxin. PHI-(14-27)-NH2 and PHI tachyphylaxis caused significant antagonism of the fall in internal anal sphincter pressure by PHI-27 and PHM-27 without modifying the IAS responses to VIP and rectal balloon distention, sacral nerve stimulation, and local intramural stimulation. On the other hand, VIP and growth hormone releasing factor analogues caused significant antagonism of VIP responses without modifying the responses to PHI-27. We conclude that distinct PHI and VIP receptors are present in the IAS smooth muscle and that PHI may not play a significant role in the IAS relaxation via the rectoanal reflex.