Enterocutaneous Fistula From A Billroth II Afferent Limb: Successful Closure With Endoclips.

Recently, indications for endoscopic clips have expanded to include closure of gastrointestinal fistulae and perforations. A 62-year-old man with remote history of surgery for peptic ulcer underwent right hemicolectomy for a large hepatic flexure mass with proximal colonic dilatation. During surgery, inadvertent pinpoint duodenotomy of the afferent Billroth II limb resulted in a duodeno-cutaneous fistula.

Anatomic classification of the endoscopic appearance of the normal appendiceal orifice: a novel tool for recognition and documentation of cecal intubation.

Complete colonoscopy for cancer screening requires cecal intubation. Failure to reach and examine the cecum may result in missed right colon pathology. We developed and validated a novel classification scheme for the endoscopic appearance of the normal appendiceal orifice (AO).

Long-term mortality and morbidity of transfusion-associated non-A, non-B, and type C hepatitis: A National Heart, Lung, and Blood Institute collaborative study.

Persons with non-A, non-B hepatitis (cases) identified in 5 transfusion studies in the early 1970s have been followed ever since and compared for outcome with matched, transfused, non-hepatitis controls from the same studies. Previously, we reported no difference in all-cause mortality but slightly increased liver-related mortality between these cohorts after 18 years follow-up. We now present mortality and morbidity data after approximately 25 years of follow-up, restricted to the 3 studies with archived original sera.

Long-term mortality after transfusion-associated non-A, non-B hepatitis. The National Heart, Lung, and Blood Institute Study Group.

Background: Acute non-A, non-B hepatitis after blood transfusion often progresses to chronic hepatitis and sometimes culminates in cirrhosis or even hepatocellular carcinoma. However, the frequency of these sequelae and their effects on mortality are not known.

Methods: We traced patients with transfusion-related non-A, non-B hepatitis who had been identified in five major prospective studies conducted in the United States between 1967 and 1980.

Differential inhibition of individual human liver cytochromes P-450 by cimetidine.

Cimetidine binds to cytochrome P-450 and inhibits hepatic metabolism of various drugs in humans. However, cytochrome P-450 is a family of enzymes rather than a single protein, and effects of cimetidine on individual human liver cytochromes P-450 have not been previously characterized. Metabolism of selected substrates and cimetidine-binding assays have been performed using human liver microsomes, purified human liver cytochromes P-450, and cytochrome P-450 complementary DNA-expressed yeast proteins to probe interaction of cimetidine with these individual enzymes.

Nodular regenerative hyperplasia: a cause of ascites and hepatomegaly after chemotherapy for leukemia.

Tender hepatomegaly and ascites occurred in a young woman receiving cytosine arabinoside and daunorubicin for acute myelogenous leukemia. Whereas veno-occlusive disease was suspected clinically, liver biopsy showed nodular regenerative hyperplasia with no evidence of hepatic vein abnormalities. It is postulated that nodular regenerative hyperplasia can be initiated by hepatotoxicity of chemotherapy agents used to treat leukemia and/or that these agents exacerbate clinical manifestations of this histological abnormality.

Caseating hepatic granulomas in Hodgkin's lymphoma.

A 68-year-old man presented with recurrent Hodgkin's lymphoma after a 9-year disease-free interval induced by chemotherapy. In addition to histological evidence of recurrent Hodgkin's disease, the liver biopsy specimen showed extensive caseating granulomas. Cultures of bone marrow and liver tissue tested negative for Mycobacterium tuberculosis.

Resolution of inferior vena cava syndrome after embolization of a hepatic adenoma.

A 77-year-old man presented with severe pruritus and massive lower body edema. Computerized axial tomography of the abdomen showed a large hepatic mass compressing the inferior vena cava, and a liver biopsy specimen showed hepatic adenoma. Embolization of vessels feeding the hepatic tumor resulted in complete resolution of pruritus and ascites, and clinical remission has persisted for 1 year following partial obliteration of tumor vasculature.

Influence of hyperalimentation on rat hepatic microsomal fluidity and function.

Total parenteral nutrition with an amino acid-glucose solution has previously been shown to decrease rat hepatic drug metabolism compared with drug metabolic activity observed in rats receiving the same solution enterally and chow-fed animals. Because changes in membrane fluidity and lipid composition are reported to influence activity of a number of liver enzymes, effects of parenteral and enteral nutrition on hepatic microsomal membrane fluidity and lipid composition were assessed and compared with hepatic mixed-function oxidase activity. Both parenteral and enteral hyperalimentation produced a significant decrease in microsomal membrane fluidity (fluorescence anisotropy = 0.

Effects of formula composition on hepatic and intestinal drug metabolism during enteral nutrition.

Significant compositional differences in protein and lipid content are present in currently available enteral nutrition preparations. Since variations in dietary protein and/or lipid have previously been shown to produce alterations in liver and gut drug metabolism, effects of five commonly used enteral nutrition regimens on several drug metabolic parameters were assessed in rats. Study formulations included: 1) Vivonex: low protein -no lipid; 2) High Protein Vivonex: normal protein -no lipid; 3) Vital: normal protein -normal lipid; 4) Sustacal: high protein -high lipid; 5) Isocal: normal protein -high lipid.

Selective alteration of constitutive hepatic cytochrome P-450 enzymes in the rat during parenteral hyperalimentation.

Decreased drug metabolism and hepatic cytochrome P-450 levels have been shown previously to occur in rats receiving total parenteral nutrition (TPN) compared to animals receiving the same hyperalimentation solution enterally (TEN). In the present studies, animals received a 7-day infusion of a 25% glucose-2.75% crystalline amino acid solution via a catheter in the jugular vein or stomach; hepatic microsomal levels of four major constitutive cytochromes P-450 were determined subsequently by immunoquantitation and correlated with metabolism of selected substrates biotransformed by these enzymes.

Oxidative metabolism of hexobarbital in human liver: relationship to polymorphic S-mephenytoin 4-hydroxylation.

The major route of hexobarbital metabolism in humans involves hydroxylation at the 3'-position followed by oxidation to a 3'-keto metabolite. Studies were performed to characterize the form of cytochrome P-450 responsible for the initial oxidation. In vitro studies indicated that P-450MP purified from human livers, involved in the 4-hydroxylation of S-mephenytoin, efficiently catalyzed the 3'-hydroxylation of hexobarbital; moreover, polyclonal antibodies raised to this enzyme extensively inhibited such activity in human liver microsomes.

Primary malignant melanoma of the rectum. Evidence for origination from rectal mucosal melanocytes.

Reports of rectal melanoma often attribute the lesion to tumor extension from anal melanocytes which have undergone malignant transformation while the existence of true primary melanoma of the rectum has been disputed. This dispute primarily relates to past inability to demonstrate normal melanocytes in rectal mucosa. In this case report, two polypoid melanomas clearly located in the rectum were discovered at sigmoidoscopy.

Newer agents available for treatment of stress-related upper gastrointestinal tract mucosal damage.

Results of animal studies and human clinical trials assessing the efficacy of newer agents in the treatment of stress-related mucosal damage have been reviewed. Currently available data suggest that prostaglandin treatment is as effective in preventing and treating stress-induced mucosal injury as more established therapeutic modalities, but that the proposed efficacy of somatostatin infusion and tranexamic acid administration is highly suspect. Promising agents yet to be evaluated include omeprazole, allopurinol, and epidermal growth factor.

Influence of gastrointestinal peptides on bile acid transport by isolated rat hepatocytes.

While numerous effects of gut peptides on gastric, pancreatic, and intestinal secretion have been described, there has been little investigation of the influence of these peptides on hepatic function. In the present studies, effects of vasoactive intestinal peptide (VIP), somatostatin, thyrotropin-releasing hormone (TRH), and bombesin on taurocholate transport by isolated rat hepatocytes have been examined. Somatostatin, TRH, and bombesin in incubation media produced no change from control incubations with regard to either uptake of taurocholate by hepatocytes or efflux of bile acid from preloaded cells.

Hepatic bile formation in the rat. Addition of vasoactive intestinal peptide to the equation.

While changes in gastric, pancreatic, and intestinal secretion in response to more recently identified gastrointestinal peptides have been characterized, there has been less investigation into effects of these hormones on hepatic bile production. The isolated perfused rat liver model has been used to examine effects of vasoactive intestinal peptide (VIP), somatostatin, bombesin, and thyrotropin-releasing hormone (TRH) on bile flow and bile acid transport. No changes were seen following bolus administration of bombesin (3 X 10(-8)-1.

Hepatic metabolism of tolbutamide: characterization of the form of cytochrome P-450 involved in methyl hydroxylation and relationship to in vivo disposition.

In vitro investigations suggest the same human liver cytochrome P-450 that catalyzes S-mephenytoin 4-hydroxylation, P-450MP, is responsible for methyl hydroxylation of the oral hypoglycemic agent tolbutamide. Tolbutamide hydroxylase activity copurified with P-450MP; electrophoretically homogenous P-450MP catalyzed both tolbutamide and S-mephenytoin hydroxylation. Each substrate competitively inhibited hydroxylation of the other, and anti-P-450MP inhibited tolbutamide hydroxylation in human liver microsomes.

Polymorphism of human cytochrome P-450.

The cytochrome P-450 forms involved in debrisoquine 4-hydroxylation (P-450DB), phenacetin O-deethylation (P-450PA), S-mephenytoin 4-hydroxylation (P-450MP), and nifedipine 1,4-oxidation (P-450NF) have been purified to electrophoretic homogeneity from human liver microsomes. All of these reactions show in vivo polymorphism in humans. Evidence for the roles of the purified proteins in these processes comes from in vitro reconstitution and immunoinhibition studies.

Stress-related mucosal damage: critical evaluation of potential new therapeutic agents.

Cell injury produced by hydrochloric acid is the final common denominator for stress-related mucosal damage. Actions of therapeutic agents designed to prevent such damage are directed toward either inhibiting acid secretion or stimulating protective mechanisms. Newer agents that fall into the former category include omeprazole, an inhibitor of the H+-K+-ATPase pump, prostaglandins, and somatostatin.

Effect of cholestasis on hepatic transport of 99mtechnetium p-isopropyl-iminodiacetic acid.

Hepatobiliary imaging with 99mTc-p-isopropyl-iminodiacetic acid (PIPIDA) and other acetanilidoiminodiacetic acid derivatives is a frequently used clinical tool in evaluating patients with jaundice. However, there has been little objective assessment of the effects of cholestasis on hepatic transport of acetanilioiminodiacetic acid derivatives. In our studies, transport of 99mTc-PIPIDA by isolated rat hepatocytes obtained from animals with extrahepatic obstruction secondary to bile duct ligation or intrahepatic cholestasis induced by ethinyl estradiol therapy was determined.

Separate influences of insulin and hyperglycemia on hepatic drug metabolism in mice with genetic and chemically induced diabetes mellitus.

Numerous investigators have reported abnormalities of hepatic drug metabolism in hypoinsulinemic animal models with chemically induced diabetes mellitus, but there has been little assessment of hepatic drug metabolism in recently described animal models with genetic diabetes mellitus characterized by hyperinsulinemia and insulin resistance rather than insulin deficiency. Hepatic microsomal cytochrome P-450 content and drug metabolizing activity in obese, diabetic C57BL/KsJ mice homozygous for the diabetes gene mutation (db/db) have been compared with levels found in livers of 1) lean, nondiabetic control mice with the same C57BL/KsJ genetic background and 2) lean C57BL/6J animals made diabetic by streptozotocin treatment. No changes in specific enzyme content or activity were seen in young db/db mice, but microsomal protein and total hepatic cytochrome P-450 content and meperidine demethylation and pentobarbital hydroxylation activity were markedly increased compared to controls.