Abnormal sensitivity to duodenal lipid infusion in patients with functional dyspepsia

BACKGROUND AND OBJECTIVES: Patients with functional dyspepsia exhibit increased sensitivity to gastric distension (mechanoreceptors) and to meals rich in fat (chemoreceptors). The aim of this study was to test whether these patients were abnormally sensitive to intraduodenal lipid, and whether this stimulus altered gastric mechanosensitivity. METHODS AND DESIGN: Experiments were conducted on 10 patients and 10 healthy controls. The stomach was distended with a flaccid bag during duodenal infusion of either 10% Intralipid or 0.9% saline. Intragastric pressure was recorded continuously, and the participants were asked to report gastric sensations of fullness and discomfort. RESULTS: Intragastric pressure profiles during distension were similar in patients and controls. Lipid decreased intragastric pressure and reduced phasic contractility. Patients showed enhanced sensitivity to gastric distension compared with controls during both saline and lipid infusions. In the controls, threshold volumes for fullness and discomfort were higher during lipid than saline infusion. In the patients, the sensation of fullness occurred at lower volumes during lipid infusion, whereas discomfort occurred at similar volumes but lower intragastric pressures. Most patients experienced nausea and bloating and three patients vomited during lipid infusion, but remained asymptomatic during saline infusion. Controls reported no symptoms during either infusion. CONCLUSION: Dyspeptic patients have increased sensitivity to both gastric distension and intraduodenal lipid. In contrast to controls, lipid sensitizes their stomachs to distension.     

H2AX phosphorylation in response to DNA double-strand break formation during bystander signalling: effect of microRNA knockdown

Upon DNA double-strand break (DSB) formation, hundreds of H2AX molecules in the chromatin flanking the break site are phosphorylated on serine residue 139, termed gamma-H2AX, so that virtually every DSB site in a nucleus can be visualised within 10 min of its formation using an antibody to gamma-H2AX. One application of this sensitive assay is to examine the induction of DNA double-strand damage in subtle non-targeted cellular effects such as the bystander effect. Here whether microRNA (miRNA) serve as a primary signalling mechanism for bystander effect propagation by comparing matched human colon carcinoma cell lines with wild-type or depleted levels of mature miRNAs was investigated. No major differences were found in the levels of induced gamma-H2AX foci in the tested cell lines, indicating that though miRNAs play a role in bystander effect manifestation, they appear not to be the primary bystander signalling molecules in the formation of bystander effect-induced DSBs.     

Interferon alpha-2b in the treatment of chronic hepatitis C: early experience

The antiviral and immunomodulatory effects of interferon were assessed in the treatment of chronic Hepatitis C in multi-ethnic patients to prevent viral replication and chronic liver damage. Three million units of recombinant interferon alpha-2b were administered three times a week for 48 weeks to a group of 9 active Hepatitis C patients. A clinical response was defined as normalization of serum ALT values. Serum was frozen and stored for Hepatitis C viral assays. Four patients normalized their liver functions. When viral levels were measured only two patients had unmeasurable levels of HCV RNA after treatment. Therapeutic results were observed and much work needs to be done to improve therapy because a serious epidemic is predicted for the future.     

Cognitive functions and aging in the dog: acquisition of nonspatial visual tasks

Child welfare practice and substance abuse treatment have become overlapping areas for many human service professionals. This article stresses the importance of combining perspectives, calling for the child welfare and alcohol and other drug (AOD) abuse treatment systems to deal with both the mother's recovery and the child's well-being. Changes in attitudes, knowledge, and skills are required on the part of both the child welfare practitioner and the AOD abuse treatment worker.     

Animal models of granulomatous inflammation

BACKGROUND: The Women and Infants Transmission Study is an ongoing prospective cohort study of HIV-infected pregnant women and their infants. We used the 1994 U.S. Centers for Disease Control and Prevention (CDC) classification system for HIV infection in children to describe HIV disease progression in 128 HIV-infected children, and examined maternal and infant characteristics associated with disease course. METHODS: The Kaplan-Meier method was used to calculate probabilities of entry into CDC clinical classes A, B, and C (mild, moderate, and severe HIV disease); CDC immunologic stages 2 and 3; and death. Relative risks of progression for selected predictor events were estimated using the Cox proportional hazards model. RESULTS: With a median 24 months of follow-up, the median ages at entry into clinical classes A, B and C were 5, 11, and 48 months, respectively. Increased risk of progression to class C was seen in infants who had: onset of class B events (p < .001); progression to immunologic stage 2 (p < .001) or 3 (p < .001); early culture positivity (in first 48 hours, p < .01; in first 7 days, p = .03); and early appearance (within the first 3 months of life) of lymphadenopathy, hepatomegaly, or splenomegaly (p < .001). CONCLUSIONS: Reaching specific clinical or immunologic stages were strong predictors of progression to AIDS or death. Early onset of clinical signs (onset of lymphadenopathy, hepatomegaly, or splenomegaly < or =3 months of age), and early culture positivity (within the first 48 hours or within the first week of life), defined the infant with highest risk of disease progression.     

Oligopeptidase B-dependent signaling mediates host cell invasion by Trypanosoma cruzi

Mammalian cell invasion by the intracellular protozoan parasite Trypanosoma cruzi is mediated by recruitment and fusion of host cell lysosomes, an unusual process that has been proposed to be dependent on the ability of parasites to trigger intracellular free calcium concentration ([Ca2+]i) transients in host cells. Previous work implicated the T.cruzi serine hydrolase oligopeptidase B in the generation of Ca2+-signaling activity in parasite extracts. Here we show that deletion of the gene encoding oligopeptidase B results in a marked defect in host cell invasion and in the establishment of infections in mice. The invasion defect is associated with the inability of oligopeptidase B null mutant trypomastigotes to mobilize Ca2+ from thapsigargin-sensitive stores in mammalian cells. Exogenous recombinant oligopeptidase B reconstitutes the oligopeptidase B-dependent Ca2+ signaling activity in null mutant parasite extracts, demonstrating that this enzyme is responsible for the generation of a signaling agonist for mammalian cells.     

Initial experience with venous stents in exertional axillary-subclavian vein thrombosis

PURPOSE: Exertional thrombosis of the axillary and subclavian veins, also known as Paget-Schr?tter syndrome, has been increasingly recognized in recent years as a cause of long-term morbidity. Recent aggressive approaches to treating Paget-Schr?tter syndrome have suggested the association of early failure with residual subclavian vein stenosis. As a result, the use of endoluminal stents has been proposed as an aid to venous percutaneous transluminal angioplasty for this disorder. METHODS: This report outlines the therapy of 11 consecutive patients with Paget-Schr?tter syndrome who were treated at our institution between October, 1992, and December, 1995. Stents were placed when percutaneous transluminal angioplasty was unsuccessful at achieving an adequate residual lumen. RESULTS: Stents were placed after initial thrombolysis in six patients and in late follow-up in two patients. Of the six patients who had stents placed at initial thrombolysis, first-rib resection was eventually performed in four. In two patients first-rib resection was not performed, and stent fracture occurred in both. Late patency was achieved in the stents of six of the eight patients. CONCLUSIONS: Trials to evaluate stents as an adjunct to conventional therapy seem warranted. The use of stents alone without first-rib resection, however, appears to be associated with stent fracture.     

An important role for the chemokine macrophage inflammatory protein-1 alpha in the pathogenesis of the T cell-mediated autoimmune disease, experimental autoimmune encephalomyelitis

Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell-mediated, inflammatory demyelinating disease of the central nervous system (CNS) that serves as a model for the human demyelinating disease, multiple sclerosis. A critical event in the pathogenesis of EAE is the entry of both Ag-specific T lymphocytes and Ag-nonspecific mononuclear cells into the CNS. In the present report we investigated the role of two C-C chemokines (macrophage inflammatory protein-1 alpha (MIP-1 alpha) and monocyte chemotactic protein-1) and a C-x-C chemokine (MIP-2) in the pathogenesis of EAE. Production in the CNS of MIP-1 alpha, but not that of MIP-2, a rodent homologue of IL-8, or monocyte chemotactic protein-1, correlated with development of severe clinical disease. Administration of anti-MIP-1 alpha, but not that of anti-monocyte chemotactic protein-1, prevented the development of both acute and relapsing paralytic disease as well as infiltration of mononuclear cells into the CNS initiated by the transfer of neuroantigen peptide-activated T cells. Ab therapy could also be used to ameliorate the severity of ongoing clinical disease. Anti-MIP-1 alpha did not affect the activation of encepahlitogenic T cells as measured by cytokine secretion, surface marker expression, and ability to adoptively transfer EAE. These results demonstrate that MIP-1 alpha plays an important role in directing the chemoattraction of mononuclear inflammatory cells in the T cell-mediated autoimmune disease, EAE.