The emergence of HIV has provoked a widespread reappraisal of infection control practices in endoscopy units. Infection control practices should be applied to all patients alike without recourse to selection or screening. Although there has only been one reported instance of viral transmission at endoscopy, HIV could in theory be transmitted by a contaminated endoscope. Experience suggests that this is more likely to occur from damaged endoscopes, if an unsuitable disinfectant is used or endoscopes are not precleaned. In-use studies have shown that HIV contaminates endoscopes used on patients with AIDS, but in amounts too small to cause infection in tissue cultures. Cleaning in neutral detergent is extremely effective in removing contaminating micro-organisms, including HIV, from endoscopes. Aldehydes are the disinfectants of choice, but any disinfectant may fail if organic material is not removed by cleaning. After thorough cleaning, short disinfection times (e.g. four minutes) ensure inactivation of all relevant micro-organisms except Cryptosporidium and mycobacteria, although in practice even these organisms are likely to be reduced to non-pathogenic levels. Accidental needlestick injuries are the greatest hazard in the endoscopy suite; needles should not be resheathed and biopsy forceps must be handled with great care. The wearing of gloves should become second nature.

Phospholipases are enzymes that hydrolyze specific portions of phospholipid molecules. Their role in the digestion of exogenous phospholipids and as the active principle in snake and bee venoms has long been appreciated. Interest has increased in phospholipases recently because of new data implicating them in the inflammatory response. The ability of phospholipases to hydrolyze bacterial phospholipids has also received considerable attention. These new data have brought pertinence to studies of the physicochemical nature of potential substrates that greatly influence enzyme activity. Interest in the regulation of enzyme activity, both by physiological and pharmacological means, has increased as the importance of the phospholipases in response to various stimuli has become better appreciated. Finally, considerable interest has focused on the role of the phospholipases in response to hormones in a variety of cell systems. Data pertinent to all of these areas of interest will be discussed in this review with a view toward stimulating those with an interest in gastrointestinal physiology to apply them to their own areas of research in the gastrointestinal tract or liver.

The molecular genetics of five common single gene and one polygenic chronic liver disease is discussed. In two of the single gene disorders, alpha 1-antitrypsin deficiency and cystic fibrosis, the gene responsible is now known and the repertoire of different mutations underlying the disease is being defined. In the other three single gene defects (haemochromatosis, polycystic liver disease and Wilson's disease) the chromosomal location of the disease allele is known. It is anticipated that recombinant DNA techniques will enable the genes responsible for these diseases to be cloned in the near future, thus allowing the biochemical abnormalities to be defined through reverse genetics. In many chronic liver diseases the relative contribution of genetic and environmental factors remains unclear. Evidence suggests there is a definite genetic component in predisposition to alcoholic cirrhosis; the role of putative candidate genes is discussed. It is hoped that the definition of a genetic locus linked to alcoholic cirrhosis will ultimately teach us more about the basic pathogenesis of this disease.

Human immunodeficiency virus (HIV) is a retrovirus infecting CD4 positive cells, causing profound immunosuppression and eventually manifesting clinically as the acquired immunodeficiency syndrome (AIDS). The cells principally infected by HIV are T4 (helper) lymphocytes and macrophages. The eventual loss of helper cell function is the prime reason for immunodeficiency, which renders the individual susceptible to opportunistic infections. Virtually every organ system in the body can be affected clinically during the course of HIV infection. The gastrointestinal tract is a major target and the physiological sequelae are an important cause of morbidity and mortality. The pathophysiology of intestinal infection is not yet fully understood but two main mechanisms have been postulated. The first is reduced intestinal immunity resulting in chronic opportunistic infections, which themselves cause altered intestinal function. The second is that HIV per se affects the intestinal mucosa, causing malfunction. The mechanisms by which the latter occurs are controversial but may result from either direct infection of mucosal epithelial cells or from macrophages within the mucosa. Reports have documented the presence of the HIV genome in both epithelial argentochromaffin cells and macrophages. In addition, profound degeneration of intrinsic jejunal autonomic neurones has been demonstrated but the functional significance of such denervation is as yet unknown. The clinical stage of HIV infection at which intestinal mucosal immunity fails is, by definition, when opportunistic infection occurs (that is, clinical progression to stage 4 disease, namely AIDS) but detailed knowledge of the aetiology of intestinal immune failure is lacking. However, protection of intestinal mucosal surfaces with antibodies against HIV, induced by vaccination using the oral or rectal route, is an area of great interest. The major site of entry of HIV is thought to be via the intestinal tract and thus protection of its surfaces may be crucial in preventing infection.

We report the case of an 18-yr-old man with quiescent ulcerative colitis complicated by concomitant primary sclerosing cholangitis and rapidly progressive glomerulonephritis. Findings on immunofluorescence microscopy and electron microscopy suggested that glomerular injury occurred secondary to the deposition of circulating immune complexes. Renal disease responded to treatment with corticosteroids. A review of the literature found similar cases of glomerulonephritis and inflammatory bowel disease, but no previous association with sclerosing cholangitis has been recognized. The pertinent clinical, immunological, and pathophysiological aspects of this association are reviewed.

We have reported the presence of c-K-ras oncogenes activated by single point mutations at codon 12 in a vast majority of human pancreatic carcinomas. Formalin-fixed, paraffin-embedded specimens from surgical resections, autopsies and biopsies were used as well as snap frozen surgical specimens. The high oncogene incidence has been confirmed in other studies and indicate that somatic mutational activation of the c-K-ras gene is an important event in the development, maintenance or progression of cancer of the exocrine pancreas. While the role that these point mutations play in any or all of these processes remains to be determined, their presence is useful clinically for the diagnosis of pancreatic carcinoma at the molecular genetic level. The detection of mutated c-K-ras oncogenes in fine needle aspirates of pancreatic masses, that by cytomorphology may be suspicious but not diagnostic of malignant disease, increases the sensitivity of the diagnosis for this cancer. The identification of codon 12 mutations in the c-K-ras gene in pancreatic adenocarcinomas has been possible by advances in recombinant DNA techniques, especially by the development of in vitro gene amplification by the polymerase chain reaction (PCR). The possibility of analysing formalin-fixed, paraffin-embedded tissue for the presence of genetic alterations as small as single point mutations by PCR in concert with other mutation detection techniques, should facilitate the molecular genetic analysis of pancreatic carcinoma. Retrospective studies using stored specimens are now feasible with the technology described and should yield important information on the molecular epidemiology and aetiology of this and other diseases.

As the pancreas and the spleen lie in close proximity, splenic complications may occur in the course of acute or chronic pancreatitis in the form of isolated splenic vein thrombosis, intrasplenic pseudocysts, splenic rupture, infarction, and necroses as well as splenic hematoma and severe bleeding from eroded splenic vessels. Diagnosis is usually made under emergency conditions and is mainly based on ultrasound and computed tomography plus bolus injection and splenoportography. Additionally, ultrasound- or computed tomography-guided needle aspiration of fluid collection in the left upper quadrant may be helpful. Such conditions may be life threatening and, according to the increasing number of case reports, may be more frequent than is thought. They must be added to the list of other important extrapancreatitic complications such as shock and respiratory and renal failure. This review summarizes the present knowledge on splenic complications in acute and chronic pancreatitis for purposes of timely diagnosis and treatment and draws attention to the need for follow-up examinations of the spleen by imaging procedures in the course of acute and chronic pancreatitis.

The central action of peptides to influence GI motility in experimental animals is summarized in Table 1. TRH stimulates gastric, intestinal, and colonic contractility in rats and in several experimental species. A number of peptides including calcitonin, CGRP, neurotensin, NPY, and mu opioid peptides act centrally to induce a fasted MMC pattern of intestinal motility in fed animals while GRF and substance P shorten its duration. The dorsal vagal complex is site of action for TRH-, bombesin-, and somatostatin-induced stimulation of gastric contractility, and for CCK-, oxytocin- and substance P-induced decrease in gastric contractions or intraluminal pressure. The mechanisms through which TRH, bombesin, calcitonin, neurotensin, CCK, and oxytocin alter GI motility are vagally mediated. An involvement of central peptidergic neurons in the regulation of gut motility has recently been demonstrated in Aplysia, indicating that such regulatory mechanisms are important in the phylogenesis. Alterations of the pattern of GI motor activity are associated with functional changes in transit. TRH is so far the only centrally acting peptide stimulating simultaneously gastric, intestinal, and colonic transit in various animals species. Opioid peptides acting on mu receptor subtypes in the brain exert the opposite effect and inhibit concomitantly gastric, intestinal, and colonic transit. Bombesin and CRF were found to act centrally to inhibit gastric and intestinal transit and to stimulate colonic transit in the rat. The antitransit effect of calcitonin and CGRP is limited to the stomach and small intestine. The delay in GI transit is associated with reduced GI contractility for most of the peptides except central bombesin that increases GI motility. Nothing is known about brain sites through which these peptides act to alter gastric emptying and colonic transit. Regarding brain sites influencing intestinal transit, TRH-induced stimulation of intestinal transit in the rat is localized in the lateral and medial hypothalamus and medial septum. The periaqueductal gray matter is a responsive site for mu receptor agonist- and neurotensin-induced inhibition of intestinal transit. The neural pathways from the brain to the gut whereby these peptides express their stimulatory or inhibitory effects on GI transit is vagal dependent with the exception of calcitonin. It is not known whether the vagally mediated inhibition of GI transit by these peptides results from a decrease activity of vagal preganglionic fibers synapsing with excitatory myenteric neurons or an activation of vagal preganglionic neurons synapsing with inhibitory myenteric neurons. The lack of specific antagonists for these peptides has hampered the assessment of their physiological role.(ABSTRACT TRUNCATED AT 400 WORDS)

Diagnostic paracentesis is a potent diagnostic tool capable of rapidly detecting portal hypertension and peritonitis. Gram's stain and chemical analysis of ascitic fluid add additional information by determining the predisposition to SBP, the presence of organisms, and the severity of peritonitis. In patients with a narrow A-GRAD, the chemical analysis, cell count and differential, and cytology will add direction for the work-up if the etiology is not apparent and confirmation if it is. This information should be available within a few hours of admission if the paracentesis and blood are obtained immediately. The results should optimize patient care and minimize costs.

Two cases of children with relapsing pancreatitis due to intramural gastrointestinal duplications with ductal communication to the pancreas are reported. A gastric duplication with ectopic pancreatic tissue was detected by endoscopic cholangiopancreatography in the gastric antrum of a 6-yr-old girl. A periampullary duodenal duplication was visualized preoperatively by duodenoscopy and computed tomography in a 10-yr-old boy. Resection of the duplication was curative in each case.