Many of the symptoms prominent in the functional gastrointestinal disorders (FGIDs) are consistent with dysfunction of the sensory and/or motor apparatus of the digestive tract. Assessment of these phenomena in man can be undertaken by using a wide variety of invasive and noninvasive techniques, some well established and others requiring further validation. By using such techniques, alterations in both sensory and motor function have been reported in the FGIDs; various combinations of such dysfunction occur in different regions of the digestive tract in the FGIDs. Our understanding of the origins of this gut sensorimotor dysfunction is gradually increasing. Thus, inflammatory, immunologic, and other processes, as well as psychosocial factors such as stress, can alter the normal patterns of sensitivity and motility through alterations in local reflex activity or via altered neural processing along the brain-gut axis. In this context, a potential role of genetic factors, early-life influences, enteric flora, dietary components, and autonomic dysfunction also should be considered in the disease model. A firm relationship between sensorimotor dysfunction and the production of symptoms, however, has been difficult to show, and so the clinical relevance of the former requires continuing exploration. Based on the conceptual framework established to date, a number of recommendations for further progress can be made.

The focus of neurogastroenterology in Rome II was the enteric nervous system (ENS). To avoid duplication with Rome II, only advances in ENS neurobiology after Rome II are reviewed together with stronger emphasis on interactions of the brain, spinal cord, and the gut in terms of relevance for abdominal pain and disordered gastrointestinal function. A committee with expertise in selective aspects of neurogastroenterology was invited to evaluate the literature and provide a consensus overview of the Fundamentals of Neurogastroenterology textbook as they relate to functional gastrointestinal disorders (FGIDs). This review is an abbreviated version of a fuller account that appears in the forthcoming book, Rome III. This report reviews current basic science understanding of visceral sensation and its modulation by inflammation and stress and advances in the neurophysiology of the ENS. Many of the concepts are derived from animal studies in which the physiologic mechanisms underlying visceral sensitivity and neural control of motility, secretion, and blood flow are examined. Impact of inflammation and stress in experimental models relative to FGIDs is reviewed as is human brain imaging, which provides a means for translating basic science to understanding FGID symptoms. Investigative evidence and emerging concepts implicate dysfunction in the nervous system as a significant factor underlying patient symptoms in FGIDs. Continued focus on neurogastroenterologic factors that underlie the development of symptoms will lead to mechanistic understanding that is expected to directly benefit the large contingent of patients and care-givers who deal with FGIDs.

6-Thioguanine nucleotide (6-TGN) levels have been proposed to correlate with inflammatory bowel disease (IBD) activity among patients treated with azathioprine or 6-mercaptopurine (6-MP). Previous studies, most with small sample sizes, yielded conflicting conclusions. Our aim was to pool the available data to provide a more precise estimate of the association between 6-TGN levels and IBD activity.

The apical membrane of the hepatocyte fulfils a unique function in the formation of primary bile. For all important biliary constituents a primary active transporter is present that extrudes or translocates its substrate toward the canalicular lumen. Most of these transporters are ATP-binding cassette (ABC) transporters. Two types of transporters can be recognized: those having endogenous metabolites as substrates (which could be referred to as "physiologic" transporters) and those involved in the elimination of drugs, toxins, and waste products. It should be emphasized that this distinction cannot be strictly made as some endogenous metabolites can be regarded as toxins as well. The importance of the canalicular transporters has been recognized by the pathologic consequence of their genetic defects. For each of the physiologic transporter genes an inherited disease has now been identified and most of these diseases have a quite serious clinical phenotype. Strikingly, complete defects in drug transporter function have not been recognized (yet) or only cause a mild phenotype. In this review we only briefly discuss the inherited defects in transporter function, and we focus on the pathophysiologic concepts that these diseases have generated.

The role of enteral nutrients in maintaining small intestinal structure and function is well established. Evidence that enteral nutrients induce intestinal adaptation include the structural and functional gradient along the length of the healthy intestine, the atrophy and functional compromise induced by fasting and parenteral nutrition, and the enhanced adaptive capacity of the distal intestine following partial enterectomy. Key mechanisms contributing to enteral nutrient-induced intestinal adaptation include nonspecific luminal stimulation and that provided by specific nutrients, "functional workload" induced by polymeric nutrients, potential stimulation of pancreaticobiliary secretions, secretion of humoral mediators, and induction of intestinal hyperemia.

Small intestinal bacterial overgrowth is common in intestinal failure. Its occurrence relates to alterations in intestinal anatomy, motility, and gastric acid secretion. Its presence may contribute to symptoms, mucosal injury, and malnutrition. Relationships between bacterial overgrowth and systemic sepsis are of potential importance in the intestinal failure patient because the direct translocation of bacteria across the intestinal epithelium may contribute to systemic sepsis: a phenomenon that has been well established in experimental animal models. The accurate diagnosis of bacterial overgrowth continues to present a number of challenges in clinical practice and especially so among patients with intestinal failure. The management of patients with bacterial overgrowth remains, for the most part, primarily empiric and comprises antibiotic therapy and correction of any associated nutritional deficiencies. Although evidence from experimental animal studies consistently indicates that probiotics exert barrier-enhancing, antibacterial, immune-modulating, and anti-inflammatory effects, which all could be benefits in small intestinal bacterial overgrowth and intestinal failure, their role in human beings remains to be evaluated adequately.

Intestinal failure-associated liver disease develops in 40% to 60% of infants who require long-term total parenteral nutrition (TPN) for intestinal failure and 15% to 40% of adults on home parenteral nutrition. The clinical spectrum includes hepatic steatosis, cholestasis, cholelithiasis, and hepatic fibrosis. Progression to biliary cirrhosis and the development of portal hypertension and liver failure occurs in a minority but is more common in infants and neonates than in adults. The pathogenesis is multifactorial. In infants it is related to prematurity, low birth weight, duration of PN, short bowel syndrome requiring multiple laparotomies, and recurrent sepsis. Other important mechanisms include lack of enteral feeding, which leads to reduced gut hormone secretion; reduction of bile flow and biliary stasis, which leads to the development of cholestasis; and biliary sludge and gallstones, which exacerbate hepatic dysfunction. In adults, IFALD is less common and related to age, length of time on PN, total caloric intake, and lipid or glucose overload. In preterm infants, a deficiency of taurine or cysteine may play a role, whereas in both adults and children, choline deficiency may exacerbate IFALD. Lipid emulsions, choline deficiency, and manganese toxicity are associated with both hepatic steatosis and cholestasis in adults and children. Management strategies for the prevention of intestinal failure-induced liver disease include early enteral feeding, a multidisciplinary approach to the management of parenteral nutrition, and aseptic catheter techniques to reduce sepsis. The addition of choline, taurine, and cysteine to PN solutions may also play a role. Oral administration of ursodeoxycholic acid may improve bile flow and reduce gallbladder stasis. Survival after either isolated small bowel or combined liver and small bowel transplantation is approximately 50% at 5 years, making this an acceptable therapeutic option in adults and children with irreversible liver and intestinal failure.

This article summarizes what is known about which factors influence survival of patients on home parenteral nutrition, the costs related to this therapy, and the quality of life for patients living on home parenteral nutrition. The article refers to both North American and European experiences with this complex therapy.

Management of home parenteral support in adult benign but chronic intestinal failure patients requires a nutrition support team using disease-specific pathways. Education of patients to ensure they self manage home parenteral nutrition (HPN) is cornerstone to obtain minimal rate of technical complications and improvement in quality of life. Nutritive mixtures, compounded by pharmacists in single "all-in-one" bags, must be tailored according to the nutritional and intestinal status of individual patients with definition of macronutrients and water-electrolyte needs, respectively. Each PN cycle should be complete in essential nutrients to be nutritionally efficient and should have sufficient amounts of amino acids, dextrose, water, minerals, and micronutrients to avoid deficiency. When the nutritional goal is achieved, a minimum number of PN cycles per week should be implemented, guided ideally by digestive balance(s) (In-Out) of macronutrients and minerals of individual patients. Indeed, HPN is, in most cases, a complementary nonexclusive mode of nutritional support. In short gut patients--who represent 75% of chronic intestinal failure patients--encouraging enteral feeding decrease PN delivery and the risk of metabolic liver disease associated with HPN. In short gut patients with no severe renal impairment, blood citrulline dosage, in association with the remnant anatomy, is a tool to delineate transient from permanent intestinal failure. The latter group includes candidates for trophic gut factors and rehabilitative or reconstructive surgery, including intestinal transplantation. Thus, outcome improvement for intestinal failure patients needs intestinal failure teams having expertise in all medical and surgical aspects of this field.