CORRESPONDENCE TO: Professor J P Galmiche, Hépato-Gastroentérologie, Hôtel Dieu, CHU de Nantes, 44035 Nantes Cedex, France (email: galmiche@easynet.fr). This consensus conference followed the rules developed by the French Agence Nationale pour le Développement de l'Evaluation Médicale (ANDEM). Briefly, this required an organising committee, a working group whose task was to make a comprehensive critical review of the literature before the conference was held, a panel of experts, and a jury. The conference was held over two days and included (a) a public session with presentations by experts working in areas relevant to the consensus questions, (b) questions and statements from conference attendees, and (c) deliberation by the jury, followed by the drafting of conclusions and recommendations. (GUT 1998;:892-898)

A greater understanding of the natural history of acute pancreatitis combined with greatly improved radiological imaging has led to improvement in the hospital mortality from acute pancreatitis, from around 25-30% to 6-10% in the past 30 years. Moreover, it is now recognised that the first phase of severe acute phase pancreatitis is a systemic inflammatory response syndrome (SIRS), during which multiple organ failure and death often supervene. Survival into the second phase may be accompanied by local complications, such as infected pancreatic necrosis, which may be prevented by prophylactic antibiotics and treated by judicious surgery. Intensive care unit costs can be substantial, but might be justified because of the excellent quality of life of survivors. Reduction in multiple organ failure by agents such as lexipafant, an antagonist of platelet activating factor (PAF) (which plays a critical role in generating the SIRS), may contribute to intensive care unit cost containment, as well as reducing the incidence of local complications and deaths from acute pancreatitis. A further improvement in the human and financial costs also requires the centralisation of the management of patients with severe acute pancreatitis, to single hospital units whose concentrated expertise equips them to intervene most effectively in what is still recognised as a highly complex disease.

Two per cent glutaraldehyde is the most commonly used disinfectant in endoscopy units within the UK. Unfortunately adverse reactions to glutaraldehyde are common among endoscopy personnel and the Health and Safety Commission has recommended substantial reductions in atmospheric levels of glutaraldehyde in order to comply with the Control of Substances Hazardous to Health Regulations, 1994. The Working Party addressed ways of eliminating or minimising exposure to glutaraldehyde in endoscopy units by reviewing alternative disinfectants and the use of automated washer/disinfectors. Alternatives to glutaraldehyde must be at least as microbicidal as glutaraldehyde, non-irritating and compatible with endoscope components and decontamination equipment. Peracetic acid is a highly effective disinfectant and may be a suitable alternative to glutaraldehyde. Peracetic acid has a vinegary-like odour and is claimed to be less irritating than glutaraldehyde. Experience with this agent remains relatively limited and the Working Party recommends that peracetic acid should be used in sealed or exhaust ventilated facilities until further experience is obtained. It is considerably more expensive than glutaraldehyde, is less stable and large volumes have to be stored. It causes cosmetic (but not functional) damage to endoscopes and is not compatible with some washer/ disinfectors. Chlorine dioxide is a powerful oxidising agent and highly effective as a disinfectant. Once activated it must be stored in sealed containers with little head space. Fumes cause irritation and sealed or exhaust ventilated facilities are necessary. The agent may damage some metallic and polymer components of endoscopes and automated washer/disinfectors and compatibility should be established with equipment manufacturers before the agent is used. Other disinfectants such as peroxygen compounds and quaternary ammonium derivatives are less suitable because of unsatisfactory mycobactericidal and/or virucidal activity, or incompatibility with endoscopes and automated washer/disinfectors. Alcohol is effective but, on prolonged contact, is damaging to lens cements. It is also flammable and therefore unsuitable for use in large quantities in automated systems. Superoxidised water (Sterilox) is an electrochemical solution (anolyte) containing a mixture of radicals with strong oxidising properties. It is highly microbicidal when freshly generated, provided items are thoroughly clean and strict generation criteria are met--that is, current, pH, redox potential. It seems to be safe for users and provided field trials substantiate laboratory efficacy tests, and the agent is non-damaging, it too may become an alternative to glutaraldehyde. When 2% glutaraldehyde is used for manual and automated disinfection, 10 minutes' immersion is recommended for endoscopes before the session and between patients. This will destroy vegetative bacteria and viruses (including hepatitis B virus (HBV) and HIV). A five minute contact period is recommended for 0.35% peracetic acid and for chlorine dioxide (1100 ppm av ClO2), but if immersed for 10 minutes sporicidal activity will also be achieved. At the end of each session 20 minutes' immersion in glutaraldehyde or five minutes in peracetic acid or chlorine dioxide is recommended. Microbiological studies show that 20 minutes of exposure to 2% glutaraldehyde destroys most organisms, including Mycobacterium tuberculosis. The Working Party concludes therefore that immersion of the endoscope in 2% glutaraldehyde for 20 minutes is sufficient for endoscopy involving patients with AIDS and other immunodeficiency states or pulmonary tuberculosis. Similarly, 20 minutes' immersion is recommended at the start of the list and between cases for endoscopic retrograde cholangiopancreatography (ERCP) when high level disinfection is required. Cleaning and disinfection of endoscopes should be undertaken by trained staff in a dedicated room. Thorough cleaning with detergent

Smooth muscle cells (SMC) of the vascular wall, bladder, myometrium, and gastrointestinal and respiratory tracts retain the ability to proliferate postnatally, which enables adaptive responses to injury, hormonal, or mechanical stimulation. SMC growth is regulated by a number of mesenchymal growth factors, including insulin-like growth factor I (IGF-I). To explore the function of IGF-I on SMC in vivo, the mouse SMC alpha-actin promotor fragment SMP8 (-1074 bp, 63 bp of 5'UT and 2.5 kb of intron 1) was cloned upstream of rat IGF-I cDNA, and the fusion gene microinjected into fertilized eggs of the FVB-N mouse strain. Mating of hemizygous mice with controls produced about 50% transgenic offspring, with equal sex distribution. Transgenic IGF-I mRNA expression was confined to SMC-containing tissue, with the following hierarchy: bladder > stomach > aorta = uterus > intestine. There was no transgene expression in skeletal muscle, heart, or liver. Radioimmunoassayable IGF-I content was increased by 3.5- to 4-fold in aorta, and by almost 10-fold in bladder of transgenic mice at 5 and 10 wk, with no change in plasma IGF-I levels. Wet weight of bladder, stomach, intestine, uterus, and aorta was selectively increased, with no change in total body or carcass weight of transgenic animals. In situ hybridization showed that transgene expression was exquisitely targeted to the smooth muscle layers of the arteries, veins, bladder, ureter, stomach, intestine, and uterus. Paracine overproduction of IGF-I resulted in hyperplasia of the muscular layers of these tissues, manifesting in remarkably different phenotypes in the various SMC beds. Whereas the muscular layer of the bladder and stomach exhibited a concentric thickening, the SMC of the intestine and uterus grew in a longitudinal fashion, resulting in a marked lengthening of the small bowel and of the uterine horns. This report describes the first successful targeting of expression of any functional protein capable of modifying the phenotype of SMC in transgenic mice. IGF-I stimulates SMC hyperplasia, leading to distinct patterns of organ remodeling in the different tissue environments.

Targeted inactivation of genes in the tumor necrosis factor (TNF)/lymphotoxin (LT) ligand and receptor system has recently revealed essential roles forthese molecules in lymphoid tissue development and organization. Lymphotoxin-alpha beta (LT alpha beta)/lymphotoxin-beta receptor (LT beta-R) signaling is critical for the organogenesis of lymph nodes and Peyer's patches and for the structural compartmentalization of the splenic white pulp into distinct B and T cell areas and marginal zones. Moreover, an essential role has been demonstrated for TNF/p55 tumor necrosis factor receptor (p55TNF-R) signaling in the formation of splenic B lymphocyte follicles, follicular dendritic cell networks, and germinal centers. In contrast to a previously described essential role for the p55TNF-R in Peyer's patch organogenesis, we show in this report that Peyer's patches are present in both TNF and p55TNF-R knockout mice, demonstrating that these molecules are not essential for the organogenesis of this lymphoid organ. Furthermore, we show that in the absence of TNF/p55TNF-R signaling, lymphocytes segregate normally into T and B cell areas and a normal content and localization of dendritic cells is observed in both lymph nodes and Peyer's patches. However, although B cells are found to home normally within Peyer's patches and in the outer cortex area of lymph nodes, organized follicular structures and follicular dendritic cell networks fail to form. These results show that in contrast to LT alpha beta signaling, TNF signaling through the p55TNF-R is not essential for lymphoid organogenesis but rather for interactions that determine the cellular and structural organization of B cell follicles in all secondary lymphoid tissues.

Three cases of apparent primary villous atrophy of the terminal ileum in women with chronic diarrhoea are reported. Eight cases have previously been reported in the literature. Clinical characteristics are the presence of severe chronic secretory diarrhoea with episodes of hypokalaemia combined with signs of ileal malabsorption and/or efficacy of cholestyramine. Diagnosis is based on ileoscopy and histology. An association with microscopic colitis was present in the three patients and in four cases in the literature. The pathogenesis of primary ileal villous atrophy remains unknown and may involve dysimmunity. Its association with microscopic colitis may indicate a common pathogenesis or support the hypothesis that the faecal stream or bile salts play a role in the pathogenesis of microscopic colitis.

Hirschsprung's disease is a neuronal dysplasia of the hindgut, characterised by a loss of neurones, which affects about 1 in 5000 live births. Genetic factors have been implicated in the aetiology of this disease in about 20% of cases and a dominant pattern of inheritance has been revealed in several families. The pathogenesis of the aganglionosis is often attributed to a failure of migration of neural crest cells, although this has not been proven. Recently, mutations in a developmentally regulated receptor tyrosine kinase gene, ret, and mutations in the endothelin receptor-B gene (ENDR-B) have both been linked to familial Hirschsprung's disease in humans. Moreover, certain mutant mouse strains--namely piebald lethal and lethal spotted--exhibit striking similarities to the human condition. The mutation which gives rise to piebald lethal has now been found to be in the ENDR-B gene, and the mutation associated with lethal spotted occurs in the gene for endothelin-3 (ET-3), a ligand for ENDR-B. Two transgenic mouse lines have been developed which also reflect the human disease: ret-k-, which has a loss of function mutation of the ret gene, and ENDR-B null. In addition, the introduction of a Lac-Z reporter gene into neural crest cells of aganglionic mice has made it possible to study directly the fate of enteric neuroblasts which are affected by "Hirschsprung's-like" mutations. Here, we review the possible roles of RET and endothelin in the normal development of the enteric nervous system, and the significance of their mutated forms in the pathogenesis of familial aganglionosis. This review focuses on recent advances in our understanding of the genetic basis of the lesions which have been implicated in congenital forms of Hirschsprung's disease. Disruption of these genes in the mouse, either by transgenic "knockout" approaches or in mutant mouse lines, offers the prospect of greater understanding of both the cellular and developmental bases of the human disease.

Elderly people commonly present with biliary tract disease. Gallstone disease is an important cause of recurrent abdominal symptoms, and we advocate an aggressive approach in stable patients not at risk to improve the quality of their lives. Choledocholithiasis is optimally treated by ERCP (98% success) even in patients who are at great risk. Endoscopic intervention often obviates the need for emergency biliary tract surgery in the elderly, is better tolerated, and is associated with significantly less risk and a lower mortality. In contrast, emergency surgery in the elderly is poorly tolerated. Even cholecystitis and biliary pancreatitis (not discussed here) are amenable to endoscopic treatment. Malignant biliary obstruction should not and cannot be treated as aggressively as benign disorders affecting the biliary tree as the long term outlook is poor. Endoscopic palliation usually suffices in maximising treatment and improving the patient's quality of life with few associated complications or postprocedural machinations (drainage bags or tubes). The afflicted population in general and the elderly in particular benefit from minimally invasive endoscopic decompression techniques.