Effect of chronic inflammation on ileal short-chain fatty acid/bicarbonate exchange.

Short-chain fatty acids (SCFA) have been demonstrated to at least partially ameliorate chronic intestinal inflammation. However, whether and how intestinal SCFA absorption may be altered during chronic intestinal inflammation is unknown. A rabbit model of chronic ileitis produced by coccidia was used to determine the effect of chronic inflammation on ileal SCFA/HCO(-)(3) exchange. SCFA/HCO(-)(3) exchange was present in the brush-border membrane (BBM) of villus but not crypt cells from normal rabbit ileum. An anion-exchange inhibitor, DIDS, significantly inhibited SCFA/HCO(-)(3) exchange. Extravesicular Cl(-) did not alter the uptake of SCFA, suggesting that SCFA/HCO(-)(3) exchange is a transport process distinct from Cl(-)/HCO(-)(3) exchange. In chronically inflamed ileum, SCFA/HCO(-)(3) exchange was also present only in BBM of villus cells. The exchanger was sensitive to DIDS and was unaffected by extravesicular Cl(-). However, SCFA/HCO(-)(3) exchange was significantly reduced in villus cell BBM vesicles (BBMV) from chronically inflamed ileum. Kinetic studies demonstrated that the maximal rate of uptake of SCFA, but not the affinity for SCFA, was reduced in chronically inflamed rabbit ileum. These data demonstrate that a distinct SCFA/HCO(-)(3) exchange is present on BBMV of villus but not crypt cells in normal rabbit ileum. SCFA/HCO(-)(3) exchange is inhibited in chronically inflamed rabbit ileum. The mechanism of inhibition is most likely secondary to a reduction in transporter numbers rather than altered affinity for SCFA.

Unique mechanism of inhibition of Na+-amino acid cotransport during chronic ileal inflammation.

In the chronically inflamed ileum, unique mechanisms of alteration of transport processes suggest regulation by different immune-inflammatory mediator pathways. We previously demonstrated that Na+-glucose cotransport in the chronically inflamed ileum was inhibited by a decrease in cotransporter number without a change in glucose affinity. The aim of this study was to determine the alterations in Na+-amino acid cotransport in chronically inflamed ileum produced by coccidial infection in rabbits. [3H]alanine uptake was performed in cells and vesicles by rapid filtration. In villus cells from chronically inflamed ileum, Na+-K+-ATPase was reduced 50% and Na+-alanine cotransport was also reduced (5.8 +/- 1.2 in normal and 1.4 +/- 0.5 nmol/mg protein in inflamed; n = 6, P < 0.05). [3H]alanine uptake in brush-border membrane vesicles was reduced in chronically inflamed ileum (73.2 +/- 1.2 in normal and 21.5 +/- 3.2 pmol/mg protein in inflamed; n = 3, P < 0.05), suggesting a direct effect on the cotransporter itself. Na+-amino acid cotransport in chronically inflamed ileum was inhibited by a decrease in affinity without a change in the maximal rate of uptake, and unaltered steady-state mRNA levels also suggested that the number of cotransporters was unchanged. Thus the mechanisms of inhibition of Na+-amino acid cotransport and Na+-glucose cotransport in chronically inflamed ileum are different. These observations suggest that different immune-inflammatory mediators may regulate different transport pathways during chronic ileitis.

Pulmonary infections in hospitalized patients with cirrhosis.

We have further characterized pulmonary infections by bronchoalveolar lavage in hospitalized patients with cirrhosis. Sixty-seven consecutive patients admitted to the Ohio State University Medical Center from 1992 to 1995 with liver disease who underwent bronchoscopy with bronchoalveolar lavage were identified. Twenty-one patients with cirrhosis and pneumonia were further analyzed. During the same period, we consecutively identified 23 patients without liver disease or immunosuppression, 19 patients with HIV infections, and 30 patients with cancer or pharmacologic immunosuppression who had bronchoscopy with bronchoalveolar lavage for pneumonia. These groups were included in these analyses as a control and immunosuppressed controls, respectively. Bronchoscopy isolated respiratory pathogens in 16 patients (76.2%) with cirrhosis and 6 patients (26.1%) in the control group (p = 0.002). Fungal organisms were most commonly found in patients with cirrhosis although several patients had more than one organism identified. The control group had mostly bacterial pathogens; the immunosuppressed controls were commonly infected with opportunistic organisms. Six (85.7%) of 7 patients with cirrhosis and fungal pneumonia died of their respiratory illness. Hospitalized patients with cirrhosis commonly have opportunistic pulmonary infections; diagnostic bronchoscopy and empiric antifungal therapy should be considered in those who do not respond to antibiotics.

Endoscopic appearance of cryptosporidial duodenitis.

Cryptosporidial oocyst infection is a common cause of diarrhea in patients with AIDS. Concomitant symptoms can include crampy abdominal pain, nausea, vomiting, and anorexia. Esophagogastroduodenoscopy is then useful for delineating potentially treatable pathogens. We report a case of cryptosporidial duodenitis with characteristic endoscopic findings, biopsy correlate, and a review of the current literature. The endoscopic appearance illustrated strongly suggests proximal small bowel mucosal involvement with cryptosporidial oocysts.

Upper-gastrointestinal bleeding from angiodysplasia of the minor papilla.

Angiodysplasia is an often unrecognized cause of upper-gastrointestinal bleeding, most commonly found in the antrum of the stomach but also in the duodenum and rarely in the esophagus. Small-intestinal angiodysplasia is the source of gastrointestinal bleeding of obscure origin in 30-40% of cases. The diagnosis is usually made by esophagogastroduodenoscopy, push enteroscopy, or selective angiography. We report the first case of angiodysplasia of the minor papilla diagnosed by side-viewing duodenoscopy.

Pancreatic tuberculosis.

Pancreatic tuberculosis is a rare clinical entity. It most often is associated with miliary tuberculosis or occurs in the immunocompromised patient and is extremely uncommon in nonendemic geographic regions. Described is a case of isolated infection of the pancreas by Mycobacterium tuberculosis occurring in an otherwise healthy individual from North America who presented with recurrent hyperamylasemia and fevers. Computerized tomography revealed a multiloculated lesion in the head of the pancreas. Intraoperative biopsies demonstrated granulomas. The diagnosis was confirmed by positive cultures. Triple drug therapy was effective in alleviating symptoms, and a follow up CT revealed a normal pancreas. One year following operation the patient remains well.

Metastatic Crohn's disease. A rare cutaneous manifestation.

Cutaneous extraintestinal manifestations of Crohn's disease are common. Lesions contiguous with the gastrointestinal tract, such as perianal, peristomal, and perifistular inflammation are characterized by the histologic demonstration of granulomas. Rarely a cutaneous granulomatous lesion occurs that is noncontiguous with the gastrointestinal tract and is separated from it by normal skin. We report axillary "metastatic" Crohn's disease that appeared with exacerbation of the inflammatory bowel disease and responded well to steroid therapy.

Gastroesophageal reflux disease: diagnosis and medical therapy.

Gastroesophageal reflux disease (GERD) is a common clinical condition that affects all age groups, particularly older adults. Its presentation is diverse and can range from occasional heartburn to disabling complications. A complete history can usually lead to the diagnosis, although further testing may be needed for refractory symptoms, complications, and atypical presentations. Multiple therapeutic options are available, and decisions governing their use are based on symptoms and severity of esophagitis. All patients should be instructed to make dietary and other lifestyle adjustments. Antacids may be needed for mild symptoms. Pharmacologic options for moderately severe cases include H2 blockers, a proton pump inhibitor, or others. Surgery is reserved for cases of severe refractory disease.

Familial Barrett's esophagus associated with adenocarcinoma.

A family with six cases of Barrett's esophagus over three generations is described. The Barrett's esophagus affected only males, and there were three associated adenocarcinomas. The mechanism of inheritance is compatible with an autosomal dominant pattern with nearly complete penetrance. Other case reports in the literature are compared with this familial case of Barrett's esophagus with associated adenocarcinomas.

Early surgical treatment of gastrinoma.

Medical treatment of the Zollinger-Ellison syndrome has been generally accepted because of the proven efficacy of the histamine (H2)-receptor antagonists in achieving symptomatic relief, and because of early reports indicating that few, if any, gastrinomas were resectable for cure. Gastrin radioimmunoassay (RIA) has made earlier and more certain diagnosis possible, and therefore reevaluation of the surgical management of gastrinomas is necessary. Experience with 60 gastrinoma patients is reported. Comparison between the pregastrin RIA years (before 1970) and post-gastrin RIA years was made to determine whether there was evidence to support the continuation of medical treatment without attempts to resect the gastrinoma. Twenty-five cases were diagnosed in the pre-RIA years. Age at diagnosis ranged from 17 to 68 years (median, 45 years). All patients were operated on. Metastases were found in 56 percent. No tumor was identified in 8 percent. Tumor was resected for "cure" (normal fasting gastrin levels for two years postoperatively) in one patient. Seventeen patients have died, and tumor was the cause of death in 70 percent. The five-year survival rate was 44 percent; the 10-year survival rate was 40 percent. Thirty-five cases were diagnosed after 1970. Age at diagnosis ranged from 39 to 61 years (median, 46 years). Thirty patients were operated on. Metastases were identified in 23 percent and no tumor was found in 17 percent. Tumor was resected for "cure" in 30 percent of patients. Seven patients have died and tumor caused death in 42 percent. The five-year survival rate was 82 percent; the 10-year rate was 64 percent. Advances in diagnosis and surgical technique since 1970 have made early operative treatment applicable in patients with gastrinoma. Because death in most cases is caused by progression of the tumor, an aggressive surgical approach to resect the tumor is advised soon after the diagnosis of Zollinger-Ellison syndrome is established.

Observations on the effect of a somatostatin analog in the Zollinger-Ellison syndrome: implications for the treatment of apudomas.

Somatostatin is known to inhibit hormone release and gastrointestinal secretion and hence may be useful in the treatment of amine precursor uptake, decarboxylase tumors. Clinical application has been limited by the short half-life, potency, and specificity of the natural hormone. Our study evaluated the effect of a synthetic analog of somatostatin, SMS 201-995 (Sandoz, Inc., E. Hanover, N.J.) on basal and stimulated gastrin release and gastric acid secretion in 10 patients with the Zollinger-Ellison syndrome. In experiment 1, H2-receptor antagonists were discontinued for 48 hours; SMS 201-995, 1 microgram/kg, was given subcutaneously; gastrin and SMS levels in plasma were determined by radioimmunoassay; and gastric secretion was measured and titrated at 0, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, and 18 hours. The mean +/- SEM baseline gastrin level (1526 +/- 733 pg/ml) was significantly inhibited for 16 hours (p less than 0.05, paired t test). Gastric secretion was neutralized for as long as 18 hours (p 0.05). In experiment 2, three patients received either a secretin (2 U/kg) or a calcium stimulation test (2 mg/kg) with or without pretreatment with SMS 201-995, 1 microgram/kg, subcutaneously. The mean +/- SEM interpreted change in gastrin (ng X 60 min/ml) without SMS 201-995, 36.8 +/- 11 (secretin), and 129 +/- 30 (calcium) were reduced with SMS 201-995 to -1.1 +/- 0.76 (secretin) and -29 +/- 28 (calcium) (p less than 0.05). In the Zollinger-Ellison syndrome, SMS 201-995 caused significant and long-lasting inhibition of both tumor gastrin release and gastric acid secretion, probably by direct action on both the gastrinoma and the stomach. SMS 201-995 blocks acid secretion and secretin- and calcium-stimulated gastrin release, indicating that SMS 201-995 inhibits peptide secretion by postreceptor mechanisms. SMS 201-995 will be useful in the palliative treatment of apudomas.

Endoscopic retrograde cholangiopancreatography in the management of pancreatic pseudocysts.

The value of ERCP was studied in 25 patients with pancreatic pseudocysts. There were no episodes of sepsis; however, acute pancreatitis developed in one patient for an overall complication rate of 4 percent. Results of ERCP were positive in 24 of the 25 patients (96 percent), with filling of the pseudocyst in 17 and pancreatic ductal obstruction in 7. Biliary tract abnormalities were found in seven patients and included common bile duct strictures in four, bile duct dilatation in two, and cystic duct obstruction in one. ERCP also detected six pseudocysts not diagnosed by ultrasonography, five of which were small and resolved with nonoperative therapy. ERCP is a safe diagnostic procedure for patients with pancreatic pseudocysts and may provide important information about coexistent biliary tract disease not otherwise available. It is also sufficiently sensitive to detect small pseudocysts that otherwise would be missed.

Sonographic measurement of the extrahepatic bile duct before and after retrograde cholangiography.

The maximum diameter of the extrahepatic bile duct visible on cholesonograms was measured immediately before and immediately after endoscopic retrograde cannulation and injection of the biliary and pancreatic ducts (ERCP) in 24 patients. Sonographic bile duct diameter increased by 3 mm or more in nine patients, all of whom had had a previous cholecystectomy. Bile duct diameter was unchanged in the remaining 15 patients, six of whom had had cholecystectomy. The technical performance of ERCP alone will alter bile duct diameter in a significant proportion of patients having endoscopic cannulation of the biliary tree. This is particularly so for patients who have had their gallbladders removed. The true diameter of the extrahepatic bile duct cannot be determined in many patients by simple measurement of images obtained at ERCP, even when corrections are made for radiographic magnification.

Pancreatic cystadenoma in Von Hippel-Lindau disease: an unusual cause of pancreatic and common bile duct obstruction.

Pancreatic cystadenoma is an unusual lesion of the pancreas, typically occurring as an isolated lesion in a middle-aged woman with abdominal pain or an asymptomatic epigastric mass. Jaundice is unusual. Two types of pancreatic cystadenoma are distinguished: microcystic and mucinous; the latter has a tendency to malignant degeneration. A patient with Von Hippel-Lindau disease and pancreatic cystadenoma developed jaundice due to common bile and pancreatic duct obstruction. Cystic and adenomatous lesions of the pancreas are common in Von Hippel-Lindau disease, but jaundice due to common bile duct obstruction has not previously been reported.

Activation of the alternative complement pathway in ascitic fluid during spontaneous bacterial peritonitis.

We studied complement and immunoglobulin profiles on the serum and ascitic fluid of a patient before and during gram-negative spontaneous bacterial peritonitis (SBP). During the infection, activation of the alternative complement pathway in ascitic fluid was manifested by a 35% reduction in functional activity and depression of both properdin and factor B concentrations to nondetectable levels. Activation of the complement cascade was also demonstrated by a 50% reduction in the C3 concentration and depression of total hemolytic complement. There was no evidence of complement activation of a functionally intact complement system in the ascitic fluid of cirrhotic patients. Complement consumption in ascitic fluid may predispose the cirrhotic to SBP.

Spontaneous bacterial peritonitis associated with acute viral hepatitis.

Spontaneous bacterial peritonitis (SBP) occurs most frequently in patients with cirrhosis and preexistent ascites; SBP has not been previously recognized in association with acute liver disease. We report two patients with acute hepatitis B infection who developed SBP. Patient 1 had Streptococcus pneumoniae peritonitis and bacteremia, but did not have ascites until after the peritoneal infection was evident. Subsequent liver biopsy and follow-up studies confirmed the clinical diagnosis of acute hepatitis. Patient 2 had submassive hepatic necrosis due to hepatitis B and developed ascites before Streptococcus fecalis SBP. Although the association of SBP with acute hepatic injury is rare, these two patients illustrate that the syndrome of SBP does occur with acute liver disease.

Surgical management of pancreas divisum.

Pancreas divisum is a congenital anatomic variant characterized by nonunion of dorsal and ventral pancreatic ducts in an otherwise fused pancreas. Of 21 patients with divisum documented by endoscopic retrograde cholangiopancreatography, 6 (28 percent) were found to have no reason other than divisum to account for multiple attacks of pancreatitis. Cholelithiasis was present in one patient, who remains free of recurrent pancreatitis after cholecystectomy only. The remaining five patients underwent surgical treatment directed at pancreas divisum in the belief that stenosis of the duct of Santorini at the entrance into the duodenum is responsible for recurrent attacks of pancreatitis. Four of five have done well with follow-up of 12, 13, 18 and 28 months. Successful sphincteroplasty of the duct of Santorini appears to prevent recurrent attacks of pancreatitis due to pancreas divisum. Pancreaticojejunostomy is reserved for those with markedly dilated ducts secondary to chronic pancreatitis.