Two patients undergoing hemodialysis for 19 and 13 yr, respectively, developed intestinal infarction with extensive amyloid deposits in the muscle layer and blood vessels. In 1 patient the deposit reacted positively with antiserum to beta 2-microglobulin by immunohistochemical stain, and therefore was classified as beta 2-microglobulin in origin. The amyloid protein of the other patient remains unclassified. In patients with gastrointestinal symptoms who have been undergoing hemodialysis for long periods of time, amyloidosis of the intestine should be considered.

The 1-year survival rates of around 70% that are now being achieved have resulted in the acceptance of liver transplantation as a treatment for end-stage liver disease. The number of patients undergoing transplantation is increasing rapidly and the indications are widening. More patients are being transplanted for acute liver failure following the recent encouraging reports of successful grafting in this condition. The proportion of patients transplanted for liver cancer is falling as it becomes apparent that 80% of patients will die from recurrent disease. The selection of candidates and timing of transplantation continue to pose difficult clinical problems. Although the surgical and anaesthetic aspects of liver transplantation have been greatly improved, the 30-day mortality remains high at around 30% and postoperative complications, especially infection and rejection, continue to be major problems. However, rehabilitation is excellent for most patients and liver transplantation should no longer be considered an experimental procedure.

A 52-yr-old woman developed exudative ascites 2 yr after the onset of peripheral neuropathy. Extensive evaluation revealed that the patient had no underlying liver disease, malignancy, infection, or cardiac or renal disease. The ascites initially responded to high-dose corticosteroid therapy. The patient had many clinical features of the recently described POEMS syndrome, including a persistent IgA lambda-paraprotein. Initially, her ascites responded to treatment with steroids. This is characteristic of the syndrome and should be considered in patients with POEMS syndrome and refractory ascites.

The maximal transport capacity (Vmax) for intestinal glucose absorption is increased in experimentally induced chronic diabetes mellitus. Using [3H]phlorizin radioautography, we examined the relation between this increase in transport Vmax and the number and distribution of sodium-glucose co-transporters on the luminal surface of rat ileum. Male Lewis rats were made diabetic with streptozocin. Ninety days later we measured 3-O-methyl-D-glucopyranose absorption and specific [3H]phlorizin binding to the ileal mucosa of the same rats. Net 3-O-methyl-D-glucopyranose flux was 6.9-fold greater in diabetic rats compared with age-matched controls. Specific binding of [3H]phlorizin to the luminal surface was 7.2-fold greater in the diabetic rats. Radioautography revealed that, in chronic diabetes, specific phlorizin binding extends into the midvillus region of the ileum, whereas in age-matched controls, it is confined to villus tips. We believe that, in untreated diabetes, a larger fraction of intestinal villus epithelial cells participate in glucose absorption.

The effect of endogenous prostaglandin inhibition on bile salt-induced colonic injury and secretion was studied microscopically and by measurements of [14C]mannitol clearance and transmural potential difference in vivo. Bile salt-induced mucosal damage and permeability increased sequentially with concentration, and these degenerative changes were accelerated with the cyclooxygenase inhibitor indomethacin. Mepacrine, a phospholipase inhibitor, gave similar results, whereas nordihydroguaiaretic acid, a lipoxygenase inhibitor, was ineffective. The effect of indomethacin was abolished by prostaglandin E2 replacement; however, exogenous prostaglandin or prior bile salt exposure failed to result in additional protection. Concentrations of bile salts below the threshold for damage elicited net secretion in the presence or absence of indomethacin, and indomethacin was also without effect on the bile salt-induced secretion at damaging concentrations. Restitution of a completely denuded surface was unaffected by indomethacin, and occurred within 30 min of recovery. The present evidence suggests that endogenous prostaglandins render the mucosa more resistant to acute injury by events independent of the repair process. In addition, the bile salt-induced secretion, which can be dissociated from increased mucosal permeability and microscopic damage, is unlikely to be the result of increased mucosal synthesis of prostaglandins.

The present study compares rat liver preservation for 9, 12, and 24 h in the standard Eurocollins solution with preservation for the same time periods in the new UW-lactobionate solution. Pharmacologic manipulation with a potent platelet-activating factor antagonist, SRI 63-441, was also evaluated. After cold storage in each of the test solutions, the livers underwent 90 min of warm, oxygenated, sanguinous perfusion. A significant increase in liver weight was noted in Eurocollins-stored versus UW-lactobionate-stored livers. After 90 min of perfusion, livers preserved in UW-lactobionate produced significantly more bile and liberated significantly less glucose and transaminases when compared with Eurocollins-stored livers. Significant augmentation of bile production was observed when donor animals were pretreated with SRI 63-441 and the livers were then stored in UW-lactobionate for 24 h. Eurocollins-stored livers demonstrated increased hepatocyte vacuolization and endothelial disruption when compared with UW-lactobionate-stored livers after 12 and 24 h of preservation. This study demonstrates the superiority of UW-lactobionate solution in liver preservation and suggests that SRI 63-441 may be beneficial in the further reduction of cold ischemic injury.

The contractile effects of 5-hydroxytryptamine on isolated portal veins and superior mesenteric veins of portal hypertensive rats (portal vein constricted) were antagonized competitively by ICI 169,369. The equilibrium dissociation constant of 1-3 nM for ICI 169,369, estimated in the veins, agrees with affinity estimates for arterial 5-hydroxytryptamine2 receptors. The receptors of portal veins of sham-operated rats had the same affinity for ICI 169,369 as the receptors of portal hypertensive rats. The systemic administration of ICI 169,369 to portal hypertensive rats decreased portal pressure from 13.0 +/- 0.4 to 11.3 +/- 0.5 mmHg (p less than 0.01) but did not affect arterial pressure. ICI 169,369 induced nonsignificant changes in both portal venous inflow and portocollateral resistance, as estimated by the radioactive microsphere technique. It is estimated that the combined changes in portal flow and resistance could explain the decrease in portal pressure. The results are consistent with an involvement of 5-hydroxytryptamine, acting through 5-hydroxytryptamine2 receptors, in prehepatic portal hypertension.

Our previous studies suggested that crypt size enlarged and that proliferation rate might be greater in the small intestine of rats during senescence. Crypt cell numbers and crypt cell proliferation rates, using the vincristine-induced metaphase arrest technique, now have been measured in the colon of aging and young Fischer 344 rats. The proximal colon of 26-28-mo-old unfasted rats had 10% more crypt cells and a higher proliferative rate than 3-4-mo-old young controls. In the distal colon, the crypt cell proliferation rate in aging rats was 56% greater than in the young. A 3-day fast reduced crypt cell proliferation about fourfold in young rats but only by 20% in aging rats. One-day refeeding abruptly increased the crypt cell population and proliferation rate in rats of both age groups. The crypt zone of proliferating cells from aging rats was broader than that seen in young rats. In addition, starvation lowered colonic crypt cell cycling rate much less in aging than in young animals. We conclude that the colons of aging rats demonstrate a hyperproliferative state and a failure to adapt appropriately to changes in food intake. These observations may be relevant to states of altered proliferation that occur in the premalignant colon.

Severe linear growth retardation occurs in 20%-30% of children with Crohn's disease, yet, it is unknown how often decreased height velocity precedes the diagnosis. The height velocities of 50 children and prepubescent adolescents with Crohn's disease were reviewed. Decreased height velocity antedated the diagnosis in 44 patients. Twenty-one patients had a reduction in height velocity before intestinal symptoms were noted. Additionally, 17 of 32 patients with attenuated linear growth had a reduction in height velocity before any weight loss. Linear growth impairment in Crohn's disease, more common than previously recognized, may precede weight loss and can be the earliest indicator of disease.

The aim of this study was to determine the range of activity and the location of lipase in the human stomach. The range of lipase activity in gastric mucosa of surgical specimens from the fundic area of 22 subjects was 594 to 3350 mU [mean, 1598 +/- 144 mU tri[3H]olein, (1 mU-1 nmol [3H]oleic acid released from tri[3H]olein per minute per milligram protein)]. For localization of activity, pinch biopsy specimens of gastric mucosa from 6 subjects were taken from the greater and lesser curvatures within 2 cm of the gastroesophageal junction (upper greater curvature and upper lesser curvature) and within 2 cm of the pylorus (lower greater curvature and lower lesser curvature). Lipase activity was higher in the upper greater curvature (405 +/- 92 mU) than in the upper lesser curvature (32 +/- 13 mU) and lowest in the antral area (16 +/- 9 mU in the lower lesser curvature and 10 +/- 2 mU in the lower greater curvature). The data show that in the human, lipase activity is localized primarily in the fundic area of the stomach. Comparison of the lipase activity levels in the gastric mucosa with lingual lipase activity levels in specimens of lingual serous glands indicates that in humans, gastric lipase is the main lipase active in the stomach.

To assess the reported association between colonic angiodysplasia and aortic stenosis, we performed a quantitative and methodologic analysis of the literature. In four controlled studies that support an association between aortic stenosis and idiopathic gastrointestinal bleeding there are major methodologic deficiencies including the following: nonblinded data collection, noncomparable diagnostic examination, nonblinded ascertainment of exposure, and noncomparable demographic susceptibility. None of the studies directly assesses angiodysplasia. Additional case reports about aortic valve replacement used to treat bleeding from angiodysplasia are limited in number and in duration of follow-up. We conclude that the existing literature does not demonstrate an association between aortic stenosis and angiodysplasia. Further controlled evaluation of this topic would be useful.

A 37-yr-old white woman from Australia presented with ascending cholangitis and jaundice and was found to have multiple brown, "earthy" pigment stones in the biliary tree, including the segmental ducts. Removal of these stones was accomplished via a subcutaneously placed afferent jejunal limb of a choledochojejunostomy using balloon dilators. The jejunal conduit also served as an access for periodic removal of newly formed stones. This combined surgical and radiologic approach is an effective way of removing recurring pigment stones. The afferent jejunal limb can also be used to perfuse dissolution agents, if necessary, via catheters placed in the biliary tree.

Anti-liver/kidney microsome1-positive sera from children with chronic active hepatitis were studied in an effort to identify the microsomal antigens selected during induction and progression of this autoimmune disease. Immunoblot analysis of sodium dodecyl sulfate gel-resolved microsomal proteins from human and rat liver using anti-liver/kidney microsome1-positive sera revealed a single polypeptide of 48 kilodaltons (human microsomes) or 50 kilodaltons (rat microsomes). Levels of the 50-kilodalton rat microsomal polypeptide were suppressed in vivo by several drugs known to modulate expression of individual forms (enzymes) of hepatic cytochrome P-450, with the largest decrease effected by phenobarbital. Dot blot analysis using a panel of 10 electrophoretically homogeneous rat liver cytochrome P-450 forms under nondenaturing conditions established that the two methylcholanthrene-inducible forms, P-450 BNF-B and P-450 ISF-G (P-450 gene subfamily IA), are selectively recognized by the anti-liver/kidney microsome1 antibodies. These findings demonstrate that sera associated with autoimmune (anti-liver/kidney microsome1) chronic active hepatitis are specifically reactive with select rat hepatic P-450 forms and suggest that these autoantibodies may be principally directed against one or more constitutive forms of the corresponding human liver cytochromes.

We conducted a double-blind, placebo-controlled, randomized treatment study in Peruvian adults with antral gastritis associated with Campylobacter pylori. Patients received either 400 mg of furazolidone (n = 14), 400 mg of nitrofurantoin (n = 24), or a placebo (n = 31) for 14 days. Endoscopy was carried out at baseline, 1 day after ceasing therapy, and 6 wk after the end of treatment to verify colonization by C. pylori and determine the extent of gastric inflammation. Treatment with nitrofurantoin or furazolidone markedly reduced or, in some cases, cleared C. pylori from the antrum (p less than 0.0005 compared with placebo). Resolution of acute gastric inflammation, as evidenced by decreased polymorphonuclear leukocyte infiltration and regeneration of the mucus layer, paralleled the reduction in bacterial colonization (p less than 0.005 compared with placebo). A high percentage of patients experienced relapse (recolonization by C. pylori and return to pretreatment levels of gastritis) within 6 wk after cessation of treatment. Significant relief of dyspeptic symptoms was not evident during the study.

A 15-yr-old girl had a life-threatening episode of toxic megacolon at age 6 yr and a life-long history of constipation and abdominal distention. A diagnosis of chronic intestinal pseudoobstruction was made. Her clinical course was that of repeated bouts of pseudoobstruction, multiple episodes of intestinal volvulus at different sites, and progressive cachexia. Histologic examination of specimens of jejunum, ileum, appendix, and colon revealed progressive fibrotic changes in intestinal smooth muscle. The abnormalities observed are most consistent with those described in progressive systemic sclerosis, but no cutaneous manifestations of this disorder have been noted in this child, and no abnormalities in other organs have been detected. Thus, this patient represents a childhood case of chronic intestinal pseudoobstruction caused by a disorder closely resembling progressive systemic sclerosis confined to the gastrointestinal tract.

The effect of nifedipine on sphincter of Oddi (SO) motor activity was determined by endoscopic manometry. Sphincter of Oddi pressures and motor function were compared in 21 healthy volunteers and in 9 patients with SO dyskinesia. The effects of sublingual doses of 10 or 20 mg of nifedipine were compared with placebo. Neither placebo nor 10 mg of nifedipine produced any effect on SO motor activity. In healthy volunteers 20 mg of nifedipine produced a moderate but significant decrease in basal SO pressure from 12.0 to 6.7 mmHg as well as in the amplitude, duration, and frequency of phasic contractions. In patients with SO dyskinesia 20 mg of nifedipine also resulted in a significant but more profound decrease of the basal SO pressure from 47.1 to 17.3 mmHg as well as in a decrease of amplitude, duration, and frequency of the phasic contractions. Neither placebo nor 10 or 20 mg of nifedipine has any effect on the sequence of phasic contractions. In summary, nifedipine may have a possible therapeutic role in the treatment of SO dyskinesia.

Recent studies of human donor livers indicate an association between ex vivo hepatocellular adenosine triphosphate and posttransplant graft function. To test the hypothesis that prior glucose loading of donor liver would optimize its adenosine triphosphate production and adenylate energy charge during ex vivo organ preservation, adult male rats were randomized to receive either intravenous dextrose or saline for 44 h. After this infusion, a liver lobe was exposed and freeze-clamped (time 0). The remaining liver was quickly flushed, excised, and stored in Collins' II solution at 2 degrees C for 8 h. Additional lobes were freeze-clamped at 1, 4, and 8 h. Liver adenosine triphosphate, total nucleoside triphosphates, and energy charge losses were significantly reduced in the dextrose-treated rats in comparison with saline-treated rats during the first 4 h of preservation. Although the livers from rats receiving intravenous dextrose were able to generate lactate, their glycogen stores were not utilized appreciably, suggesting that exogenous glucose served as a substrate for anaerobic glycolysis. Unesterified choline levels of the fasted rat livers were significantly higher than those from the rats receiving intravenous dextrose by the first hour, indicative of increased membrane breakdown. These results indicate that prior infusion of glucose enhances the capacity of the ex vivo liver, presumably through the induction and stabilization of key glycolytic enzymes, to anaerobically generate adenosine triphosphate. Administration of glucose to liver donors before organ procurement may improve post-transplant graft function by reducing the loss of hepatocellular energy, retarding membrane damage, and fostering glycogen storage for use in the early postoperative period.