Citations

AbstractBackgroundProper management of small bowel obstruction (SBO) requires a methodology to prevent nontherapeutic laparotomy while minimizing the chance of overlooking strangulation obstruction causing intestinal ischemia. Our aim was to identify preoperative risk factors associated with strangulating SBO and to develop a model to predict the need for operative intervention in the presence of an SBO. Our hypothesis was that free intraperitoneal fluid on computed tomography (CT) is associated with the presence of bowel ischemia and need for exploration.MethodsWe reviewed 100 consecutive patients with SBO, all of whom had undergone CT that was reviewed by a radiologist blinded to outcome. The need for operative management was confirmed retrospectively by four surgeons based on operative findings and the patient’s clinical course.ResultsPatients were divided into two groups: group 1, who required operative management on retrospective review, and group 2 who did not. Four patients who were treated nonoperatively had ischemia or died of malignant SBO and were then included in group 1; two patients who had a nontherapeutic exploration were included in group 2. On univariate analysis, the need for exploration (n = 48) was associated (p < 0.05) with a history of malignancy (29% vs. 12%), vomiting (85% vs. 63%), and CT findings of either free intraperitoneal fluid (67% vs. 31%), mesenteric edema (67% vs. 37%), mesenteric vascular engorgement (85% vs. 67%), small bowel wall thickening (44% vs. 25%) or absence of the “small bowel feces sign” (so‐called fecalization) (10% vs. 29%). Ischemia (n = 11) was associated (p < 0.05 each) with peritonitis (36% vs. 1%), free intraperitoneal fluid (82% vs. 44%), serum lactate concentration (2.7 ± 1.6 vs. 1.3 ± 0.6 mmol/l), mesenteric edema (91% vs. 46%), closed loop obstruction (27% vs. 2%), pneumatosis intestinalis (18% vs. 0%), and portal venous gas (18% vs. 0%). On multivariate analysis, free intraperitoneal fluid [odds ratio (OR) 3.80, 95% confidence interval (CI) 1.5–9.9], mesenteric edema (OR 3.59, 95% CI 1.3–9.6), lack of the “small bowel feces sign” (OR 0.19, 95% CI 0.05–0.68), and a history of vomiting (OR 4.67, 95% CI 1.5–14.4) were independent predictors of the need for operative exploration (p < 0.05 each). The combination of vomiting, no “small bowel feces sign,” free intraperitoneal fluid, and mesenteric edema had a sensitivity of 96%, and a positive predictive value of 90% (OR 16.4, 95% CI 3.6–75.4) for requiring exploration.ConclusionClinical, laboratory, and radiographic factors should all be considered when making a decision about treatment of SBO. The four clinical features—intraperitoneal free fluid, mesenteric edema, lack of the “small bowel feces sign,” history of vomiting—are predictive of requiring operative intervention during the patient’s hospital stay and should be factored strongly into the decision‐making algorithm for operative versus nonoperative treatment.

Patient safety is a complex issue that is constantly evolving. Communication via standardized drug ordering is recognized as one of the key elements for providing a safer hospital stay, as well as a stronger patient outcome. This feature provides examples of standardized drug prescribing and a forum for discussion. If you have a template that you believe may be beneficial to other hospital pharmacies, please submit it along with answers to the questions (as shown in the text of this article) to Joyce Generali, Director of Drug Information, Kansas University Medical Center, 3901 Rainbow Boulevard, Mail Stop 4040, Kansas City, KS 66160 or e-mail jgeneral@kumc.edu .

Insulin stimulates glucose transport in fat and skeletal muscle cells primarily by inducing the translocation of GLUT4 (glucose transporter isoform 4) to the PM (plasma membrane) from specialized GSVs (GLUT4 storage vesicles). Glycosphingolipids are components of membrane microdomains and are involved in insulin-regulated glucose transport. Cellular glycosphingolipids decrease during adipocyte differentiation and have been suggested to be involved in adipocyte function. In the present study, we investigated the role of glycosphingolipids in regulating GLUT4 translocation. We decreased glycosphingolipids in 3T3-L1 adipocytes using glycosphingolipid synthesis inhibitors and investigated the effects on GLUT4 translocation using immunocytochemistry, preparation of PM sheets, isolation of GSVs and FRAP (fluorescence recovery after photobleaching) of GLUT4–GFP (green fluorescent protein) in intracellular structures. Glycosphingolipids were located in endosomal vesicles in pre-adipocytes and redistributed to the PM with decreased expression at day 2 after initiation of differentiation. In fully differentiated adipocytes, depletion of glycosphingolipids dramatically accelerated insulin-stimulated GLUT4 translocation. Although insulin-induced phosphorylation of IRS (insulin receptor substrate) and Akt remained intact in glycosphingolipid-depleted cells, both in vitro budding of GLUT4 vesicles and FRAP of GLUT4–GFP on GSVs were stimulated. Glycosphingolipid depletion also enhanced the insulin-induced translocation of VAMP2 (vesicle-associated membrane protein 2), but not the transferrin receptor or cellubrevin, indicating that the effect of glycosphingolipids was specific to VAMP2-positive GSVs. Our results strongly suggest that decreasing glycosphingolipid levels promotes the formation of GSVs and, thus, GLUT4 translocation. These studies provide a mechanistic basis for recent studies showing that inhibition of glycosphingolipid synthesis improves glycaemic control and enhances insulin sensitivity in animal models of Type 2 diabetes.

Abstract Productive T cell activation requires efficient reorganization of the actin cytoskeleton. We showed previously that the actin-regulatory protein, hematopoietic lineage cell-specific protein 1 (HS1), is required for the stabilization of F-actin and Vav1 at the immunological synapse and for efficient calcium responses. The Tec family kinase IL-2-inducible T cell kinase (Itk) regulates similar aspects of T cell activation, suggesting that these proteins act in the same pathway. Using video microscopy, we show that T cells lacking Itk or HS1 exhibited similar defects in actin responses, extending unstable lamellipodial protrusions upon TCR stimulation. HS1 and Itk could be coimmunoprecipitated from T cell lysates, and GST-pulldown studies showed that Itk’s Src homology 2 domain binds directly to two phosphotyrosines in HS1. In the absence of Itk, or in T cells overexpressing an Itk Src homology 2 domain mutant, HS1 failed to localize to the immunological synapse, indicating that Itk serves to recruit HS1 to sites of TCR engagement. Because Itk is required for phospholipase C (PLC)γ1 phosphorylation and calcium store release, we examined the calcium signaling pathway in HS1−/− T cells in greater detail. In response to TCR engagement, T cells lacking HS1 exhibited diminished calcium store release, but TCR-dependent PLCγ1 phosphorylation was intact, indicating that HS1’s role in calcium signaling is distinct from that of Itk. HS1-deficient T cells exhibited defective cytoskeletal association of PLCγ1 and altered formation of PLCγ1 microclusters. We conclude that HS1 functions as an effector of Itk in the T cell actin-regulatory pathway, and directs the spatial organization of PLCγ1 signaling complexes.

A 58-year-old nonsmoker female was referred for evaluation of chronic cough of 13 months duration. After an initial work-up, the patient was diagnosed to have chronic cough due to eosinophilic bronchitis. The diagnostic work-up for eosinophilic bronchitis and bronchial biopsy is discussed. Eosinophilic bronchitis is differentiated from asthma. In addition, the patient developed dyspnea, flushing, and wheezing after the administration of adenosine during a cardiac stress test in spite of a negative methacholine challenge. This indirect stimulus of airway hyperresponsiveness suggests the possible involvement of mast cells in eosinophilic bronchitis.