Emergency subtotal hepatectomy: a new concept for acetaminophen-induced acute liver failure: temporary hepatic support by auxiliary orthotopic liver transplantation enables long-term success

INTRODUCTION: Acetaminophen (paracetamol) overdose (AOD) has recently emerged as the leading cause of acute liver failure (ALF) in the United States, with an incidence approaching that seen in the United Kingdom. We describe a new way to treat AOD ALF patients fulfilling King's College criteria for "super-urgent" liver transplantation. METHODS: Beginning in June 1998, we have been piloting a clinical program of subtotal hepatectomy and auxiliary orthotopic liver transplantation (ALT) for AOD ALF. Our technique is based on the following principles: (1) subtotal hepatectomy; (2) auxiliary transplantation of a whole liver graft; (3) gradual withdrawal of immunosuppression after recovery. Results were compared with patients who had undergone an orthotopic liver transplantation (OLT) for AOD ALF in the same period. Quality of life comparisons were made using the SF36 questionnaire. RESULTS: Thirteen patients underwent this procedure between June 1998 and March 2005. Median survival is 68 months (range, 0-102 m). Actual survival data show that 9 of 13 patients are alive (69%) compared with 7 of 13 OLT patients (54%). One ALT patient required a retransplantation with an OLT due to hepatic vein thrombosis, and immunosuppression is therefore maintained. The other 8 surviving ALT patients are off immunosuppression. These 8 ALT patients have normal liver function and have a better quality of life compared with the 7 surviving OLT patients. CONCLUSION: Our results with this new technique are encouraging: 69% actual survival, no long-term immunosuppression requirement, and improved quality of life in the 62% successful cases.     

Different cytokine response of primary colonic epithelial cells to commensal bacteria

AIM: To determine if primary murine colonic epithelial cells (CEC) respond to commensal bacteria and discriminate between different types of bacteria. METHODS: A novel CEC: bacteria co-culture system was used to compare the ability of the colonic commensal bacteria, Bacteroides ovatus, E coli(SLF) and Lactobacillus rhamnosus (LGG) to modulate production of different cytokines (n = 15) by primary CEC. Antibody staining and flow cytometry were used to investigate Toll-like receptor (TLR) expression by CEC directly ex vivo and TLR responsiveness was determined by examining the ability of TLR ligands to influence CEC cytokine production. RESULTS: Primary CEC constitutively expressed functional TLR2 and TLR4. Cultured in complete medium alone, CEC secreted IL-6, MCP-1 and IP-10 the levels of which were significantly increased upon addition of the TLR ligands peptidoglycan (PGN) and lipopolysaccharide (LPS). Exposure to the commensal bacteria induced or up-regulated different patterns of cytokine production and secretion.E coli induced production of MIP-1α/β and p defensin3 whereas B. ovatus and L. rhamnosus exclusively induced MCP-1 and MIP-2α expression, respectively. TNFa, RANTES and MEC were induced or up-regulated in response to some but not all of the bacteria whereas ENA78 and IP-10 were up-regulated in response to all bacteria. Evidence of bacterial interference and suppression of cytokine production was obtained from mixed bacterial: CEC co-cultures. Probiotic LGG suppressed E coli- and B. ovatus-induced cytokine mRNA accumulation and protein secretion. CONCLUSION: These observations demonstrate the ability of primary CEC to respond to and discriminate between different strains of commensal bacteria and identify a mechanism by which probiotic bacteria (LGG) may exert anti-inflammatory effects in vivo.     

Identification of Histoplasma capsulatum from culture extracts by real-time PCR

We designed and tested a real-time LightCycler PCR assay for Histoplasma capsulatum that correctly identified the 34 H. capsulatum isolates in a battery of 107 fungal isolates tested and also detected H. capsulatum in clinical specimens from three patients that were culture positive for this organism.     

The incidence of H deficient A2 and A2B bloods and family studies on the AH-ABH status of an Aint and some new variant blood types (Aint H-A1, A2-HWA1, A2BHWA1B and A2-BHWA2B)

Abstract. The incidence of H deficient A₂ blood samples in the Sheffield area was found to be 1 in 169 and 1 in 13 of group A₂ and A₂B blood samples respectively. Family studies are described on an A_int and on examples of the new variant phenotypes, A_intH↓., A_2↑HW, A_2↑B_H^W and A₂B_H^W. The sera of some of the variants contained cold anti-H^s/HI^s/HI^c/Le^bH antibodies, but none contained the Bombay type of anti-H^s active at 37°C. The authors suggest that the modified A status of most of the variants is due to reduced expression of the A₁ genes as a result of insufficient production of H precursor substance by weak H alleles. In paternity testing, it is important that an exclusion should not be based on the occurrence of an A₁ child of a not A₁ group A mating until the A₂/A₂B parent(s) have been shown to have a normal H status.     

An interchangeable role for kainate and metabotropic glutamate receptors in the induction of rat hippocampal mossy fiber long‐term potentiation in vivo

The roles of both kainate receptors (KARs) and metabotropic glutamate receptors (mGluRs) in mossy fiber long‐term potentiation (MF‐LTP) have been extensively studied in hippocampal brain slices, but the findings are controversial. In this study, we have addressed the roles of both mGluRs and KARs in MF‐LTP in anesthetized rats. We found that MF‐LTP could be induced in the presence of either GluK1‐selective KAR antagonists or group I mGluR antagonists. However, LTP was inhibited when the group I mGluRs and the GluK1‐KARs were simultaneously inhibited. Either mGlu1 or mGlu5 receptor activation is sufficient to induce this form of LTP as selective inhibition of either subtype alone, together with the inhibition of KARs, did not inhibit MF‐LTP. These data suggest that mGlu1 receptors, mGlu5 receptors, and GluK1‐KARs are all engaged during high‐frequency stimulation, and that the activation of any one of these receptors alone is sufficient for the induction of MF‐LTP in vivo. © 2015 The Authors Hippocampus Published by Wiley Periodicals, Inc.