Range Of Gastrointestinal Disorders Research Articles

Extrinsic primary afferent signalling in the gut

Visceral sensory neurons activate reflex pathways that control gut function and also give rise to important sensations, such as fullness, bloating, nausea, discomfort, urgency and pain. Sensory neurons are organised into three distinct anatomical pathways to the central nervous system (vagal, thoracolumbar and lumbosacral). Although remarkable progress has been made in characterizing the roles of many ion channels, receptors and second messengers in visceral sensory neurons, the basic aim of understanding how many classes there are, and how they differ, has proven difficult to achieve. We suggest that just five structurally distinct types of sensory endings are present in the gut wall that account for essentially all of the primary afferent neurons in the three pathways. Each of these five major structural types of endings seems to show distinctive combinations of physiological responses. These types are: 'intraganglionic laminar' endings in myenteric ganglia; 'mucosal' endings located in the subepithelial layer; 'muscular-mucosal' afferents, with mechanosensitive endings close to the muscularis mucosae; 'intramuscular' endings, with endings within the smooth muscle layers; and 'vascular' afferents, with sensitive endings primarily on blood vessels. 'Silent' afferents might be a subset of inexcitable 'vascular' afferents, which can be switched on by inflammatory mediators. Extrinsic sensory neurons comprise an attractive focus for targeted therapeutic intervention in a range of gastrointestinal disorders.

Extraintestinal complications of inflammatory bowel disease.

Recent studies of extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) have demonstrated the importance of genetic predisposition in the etiology of musculoskeletal and cutaneous manifestations. In addition, small studies have shown infliximab to be effective in treating troublesome EIMs, particularly in pyoderma gangrenosum. Other trials have examined the safety of cyclooxygenase-2-specific nonsteroidal inflammatory drugs in IBD. Further work has been done on osteoporosis in IBD, and the American Gastroenterological Association has published a technical review and management guidelines for osteoporosis in a range of gastrointestinal disorders. However, despite further publications, debate remains concerning whether IBD patients with osteoporosis have a significant increase in fracture risk, and whether the bone loss is related to the disease or to its treatment.

New methods for the diagnosis of enteric infections

Gastrointestinal disease remains a major cause of mortality and morbidity throughout the world. Recently, a number of viral, bacterial, and protozoan agents have been identified which can cause a range of gastrointestinal disorders. The effective management of these diseases requires the prompt identification of the infecting micro-organism and the early institution of preventative and therapeutic interventions. The detection of infecting microorganisms in fecal and intestinal fluids presents a particular challenge to the diagnostic microbiologist. Cultivation can be difficult due to the fastidious nature of the microorganisms and the presence of cytotoxic materials in the specimen. In the past, immunoassays have been used for the detection of some microorganisms. However, immunoassays have limited sensitivity and cannot detect all infecting microorganisms. Recently, nucleic acid amplification techniques have been developed for the direct detection of pathogenic microbial DNA and RNA in human body fluids. We have found that these methods can be applied for the accurate detection of intestinal vlruses provided that inhibitors of enzymatic amplification are removed from the sample. Using affinity binding purification and non-isotopic DNA measurement techniques, we have developed sensitive and specific assays for the quantitation of a wide range of infecting microorganisms in intestinal fluids. Nucleic acid amplification provides a Abstract continued on next page unique tool for the study of enteric pathogens and for the development of strategies for their eventual elimination from the human environment.