|| Checking for direct PDF access through Ovid
The art of diagnosis has increasingly moved away from the clinician because of advances within other branches of medicine, which have conventionally been viewed as support services (e.g., microbiology, radiology, clinical biochemistry). In clinical biochemistry, the knowledge explosion in molecular biology has begun to alter the direction of service provision. Nevertheless, there remains a place for development of ideas and techniques along conventional lines to detect or characterize disease. Gastroenterologists caring for adults have been predictably slow to accept some of these developments and continue to rely heavily on direct visualization and sampling of the intestine, despite the fact that this only provides a static morphologic picture with little or no functional information. Pediatric gastroenterologists on the other hand do not have the same privilege of unrestricted use of invasive procedures.The general philosophy underlying the development of noninvasive gastroenterological tests is to provide a reliable method for the assessment of intestinal physiology and function; the detection of intestinal disease either on an individual patient basis or as part of a screening program; the confirmation of diagnosis and monitoring response to therapy (e.g., gluten withdrawal and challenge in coeliac disease); to provide prognostic information; and to assess the etiology and pathogenesis of various intestinal diseases.The prototype of such tests was the development of methods for the noninvasive assessment of intestinal permeability (1). These tests are now widely used for research purposes, but clinical acceptance has been slow because of perceived nonspecificity of the results, the complexity of test marker analysis, confusion over optimal test dose composition, the need for timed urinary collections, and the fact that symptomatic small bowel diseases are rare (2).Analysis of fecal markers, however unpleasant this may seem, is a rapidly evolving field. This approach has the potential to provide information on the whole gastrointestinal tract or on the function of the pancreas or liver. Assessing markers of inflammation (or surrogate markers) in feces is of particular interest because many intestinal diseases have an inflammatory component that may be difficult to assess because of the location and patchy distribution of the disease. Fecal tests are, of course, not new. Initially there was direct microscopy of stool for neutrophil content, followed by chemical analysis for various compounds, osmolarity, among others. More recently, measurement of inflammatory markers (such as tumor necrosis factor α (TNF-α), neutrophil esterase, interleukins) has been advocated, but these methods suffer from the degradation of the markers within the intestine. Analysis of markers in whole-gut lavage improved diagnostic yield significantly (3), but the ingestion of large quantities of polyethylene glycol–based purgatives was problematic unless one lived in Edinburgh!The introduction of indium-111-labeled white cells (and later technicium-99 labeling), which allows accurate localization and quantitation (applies to indium labeling only) of intestinal inflammation was a major landmark (4). However, this method, which involved complete 4-day fecal collections, was demanding on patients and was associated with substantial radiation exposure and cost, and its use has, therefore, largely been limited to a few research centers. Following on from this, an attempt was made to identify other neutrophil-specific markers in stool. Ideally, such a marker should not be subject to bacterial degradation, but, if degradation occurs, the measured epitope of the molecule should remain intact. Two such markers have been identified in human subjects: lactoferrin (5), which is found predominantly within neutrophil granules and can be measured by radioimmunoassay; and calprotectin. Calprotectin is a stable protein that accounts for about 60% of the neutrophil cytosolic protein and is quantitated by an enzyme-linked immunosorbent assay (ELISA) method (now commercially available) in stool extracts (6).