Endoscopic outcomes analysis.

Endoscopic outcomes analysis has become an increasingly important topic as attempts to measure outcomes, define costs, and compare the relative costs and benefits of different diagnostic and therapeutic procedures have become a major focus of the health care community. This article (1) defines the potential benefits and medical effects of endoscopy; (2) reviews the economic and social pressures fostering the increased focus on health care outcomes research; (3) explores the basic principles, approaches, and paradigms used in health care outcomes analysis; and (4) illustrates how health care outcomes research can help to guide therapeutic approaches, such as endoscopy, in patients with abdominal pain or inflammatory bowel disease.

Access to intracellular calcium during development in the feline gastric antrum.

Circular smooth muscle cells from the feline newborn antrum, unlike the adult, are unable to respond to myogenic agonists in the absence of extracellular calcium or to exogenous inositol 1,4,5-trisphosphate (IP3). This study examined the reasons behind the relative inaccessibility of intracellular calcium stores in the newborn period. IP3 binding was determined in antral smooth muscle homogenates from adult cats and newborns by evaluating the competitive binding of D-myo-[3H]IP3 and unlabeled IP3. Receptor density (Bmax) (fmol/mg of protein) and binding affinity (Kd) were determined. The Kd was similar in adults (31 +/- 4 nM) and newborns (28 +/- 7 nM); however, the Bmax was markedly decreased in the newborn (647 +/- 181.0 fmol/mg) compared with the adult (1755 +/- 275 fmol/mg). In adult and newborn antral cells, thapsigargin, which causes a net release of Ca2+ from intracellular stores by inhibiting Ca(2+)-ATPase-dependent reuptake activity, caused an early contraction at 30 s that was maintained for at least 20 min. We conclude that, in the newborn, dynamic intracellular calcium stores are present in the smooth muscle of the feline antrum and that differences in accessibility of intracellular calcium stores may be related to changes in the release of calcium from IP3-sensitive stores.

Signal transduction pathways associated with contraction during development of the feline gastric antrum.

BACKGROUND & AIMS: Unlike adult antral cells, feline newborn antral cells are unable to contract in response to agonists in the absence of extracellular calcium or in response to exogenous inositol 1,4,5-triphosphate (IP3) after permeabilization. Changes in intracellular pathways that are associated with these differences were examined. METHODS: In adult and kitten antrum isolated smooth muscle cell contraction, levels of 1,2-diacylglycerol (DAG) and IP3 were assessed in response to cholecystokinin (CCK). RESULTS: CCK-induced contraction was transient in the adult and sustained in the kitten. U73122 blocked contraction in adult antral cells but not kitten antral cells. In adult antral tissue, CCK (10(-7) mol/L) caused an early transient increase in the level of DAG, whereas in the newborn antrum, CCK (10(-7) mol/L) caused a sustained increase in the DAG level for up to 4 minutes. IP3 showed an early increase in both age groups. Newborn contraction is associated with an initial increase in IP3 and sustained elevation of DAG levels, whereas in adult antral cells, there is a transient increase in both IP3 and DAG. CONCLUSIONS: The relative inaccessibility of intracellular calcium stores in the newborn is associated with age-related differences in signal transduction pathways.

Colonoscopy or sigmoidoscopy as the initial evaluation of pediatric patients with colitis: a survey of physician behavior and a cost analysis.

BACKGROUND: Pediatric patients presenting with colitis, suggestive of inflammatory bowel disease, undergo evaluation with either flexible sigmoidoscopy or colonoscopy. Our objectives were to assess current practice behavior in the evaluation of pediatric patients with colitis and to determine whether flexible sigmoidoscopy or colonoscopy was more cost-effective as the initial evaluation. METHODS: Practice behavior and procedure charges were assessed using a nationwide survey, and costs for diagnostic strategies were compared using a decision analysis program. RESULTS: The vast majority of survey respondents would proceed with colonoscopy if colitis suggestive of Crohn's disease was noted in the rectosigmoid area (81%) or if ulcerative colitis extended proximal to the rectosigmoid area (70%). If colonoscopy would follow if flexible sigmoidoscopy suggested either ulcerative colitis or Crohn's disease (67%), then colonoscopy would result in a savings of 23%. If the evaluation was predetermined to be limited to flexible sigmoidoscopy (16%), then flexible sigmoidoscopy was the cost-effective strategy with savings of 29%. If colonoscopy would follow flexible sigmoidoscopy for Crohn's colitis only (13%), there was no clear cost advantage. CONCLUSIONS: The most cost-effective strategy depends on the physician's need to know the disease location. Our survey results indicate that most physicians chose to establish the extent of disease in both ulcerative colitis and in Crohn's disease; thus initial colonoscopy would be the more cost-effective strategy. When knowledge of disease distribution is not essential for patient care, flexible sigmoidoscopy can lead to substantial cost savings.

Halothane and octanol block Ca2+ oscillations in pancreatic acini by multiple mechanisms.

This study has investigated halothane and octanol, reported inhibitors of gap junction permeability, for their effects on acinar cell intracellular Ca2+ concentration ([Ca2+]i) signaling. Halothane and octanol alone at maximal concentrations induced a sustained rise in [Ca2+]i of 23 +/- 4 and 29 +/- 5 nM, respectively. Cholecystokinin (CCK, 20 pM) induced [Ca2+]i oscillations in single acinar cells within the acinus to a peak of 275 +/- 17 nM, rising from a basal level of 55 +/- 3 nM. These oscillations were completely abolished by superfusion with both halothane (4 mM) and octanol (1 mM), concentrations that blocked the spread of Lucifer yellow from cell to cell within an acinus. Lower concentrations of octanol markedly reduced the oscillation frequency (0.2 and 0.5 mM octanol: reduction in oscillation frequency of 69 +/- 6 and 43 +/- 6%, respectively). These agents however, over the same concentration range, also exhibited similar inhibitory effects on [Ca2+]i oscillations in single cells dispersed from the acinus (reduction in oscillation frequency of 75 +/- 10 and 32 +/- 12% for 0.2 and 0.5 mM octanol, respectively), suggesting additional effects other than on gap junctions. Halothane inhibited inositol 1,4,5-trisphosphate [Ins(1,4,5)P3] production in response to both 1 and 10 nM CCK (31 and 40% inhibition, respectively), possibly explaining its effects on [Ca2+]i oscillations, whereas octanol showed no significant inhibition. Octanol, unlike halothane, blocked Ins(1,4,5)P3-induced Ca2+ release from permeabilized acini, an effect that was most pronounced at a more physiological Ins(1,4,5)P3 concentration. Octanol did not affect Ins(1,4,5)P3 binding to Ins(1,4,5)P3 receptor preparation. In conclusion, although halothane and octanol block gap junction permeability in pancreatic acinar cells, these agents also affect Ins(1,4,5)P3 production and Ca2+ mobilization in response to agonist stimulation.