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Roger Williams - One of the best experts on this subject based on the ideXlab platform.
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Tumour necrosis factor production in Fulminant Hepatic Failure: relation to aetiology and superimposed microbial infection.
Clinical and Experimental Immunology, 2008Co-Authors: M. De La Mata, Anthony Meager, N. Rolando, H. M. Daniels, K T Nouri-aria, A. K. J. Goka, A. L. W. F. Eddleston, G J Alexander, Roger WilliamsAbstract:SUMMARY Tumour necrosis factor-alpha (TNF-α), a cytokine derived from macrophages, is considered to bean important endogenous mediator of endotoxic shock. Patients with Fulminant Hepatic Failure are particularly susceptible to infection and the development of multi-organ Failure and similarities to endotoxic shock suggest a possible pathogenetic role for TNF in Fulminant Hepatic Failure. In vitro TNF production was therefore investigated serially in 21 consecutive patients with Fulminant Hepatic Failure and in 21 healthy controls. Spontaneous and lipopolysaccharide-stimulated TNF production were elevated in viral-induced Fulminant Hepatic Failure, compared with healthy controls (P < 0.05 and P
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Fulminant Hepatic Failure.
Current Treatment Options in Gastroenterology, 2005Co-Authors: Jelica Kurtovic, Stephen M. Riordan, Roger WilliamsAbstract:: The rare but potentially devastating clinical syndrome of Fulminant Hepatic Failure has as its components severe encephalopathy and finally cerebral edema, hemodynamic instability, renal Failure, coagulopathy, profound metabolic disturbances and a particular susceptibility to bacterial and fungal infection. Despite advances in medical management, Fulminant Hepatic Failure in its most severe form carries a high mortality rate unless urgent orthotopic liver transplantation is carried out. However, availability of cadaveric donor organs is limited and, due to the rapidly progressive clinical course in many cases, a substantial proportion of patients will die or develop contraindications to transplantation before the procedure can be performed. Consequently, recent interest has centred on living donor transplantation and the possibility of providing temporary liver support, either through auxiliary partial organ transplantation, extracorporeal perfusion or transplantation of hepatocytes, to allow time for either a liver graft to become available or native liver regeneration, on which spontaneous survival ultimately depends, to occur.
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Plasma Inhibitory Activity against Tumour Necrosis Factor in Fulminant Hepatic Failure
Clinical Science, 1996Co-Authors: Helen M. Keane, Robin D. Hughes, Nick Sheron, J. Goka, Roger WilliamsAbstract:1. Soluble tumour necrosis factor receptors released into the circulation inhibit the effects of excess tumour necrosis factor-alpha and represent an important protective response. 2. In this study we have measured the levels of tumour necrosis factor and soluble tumour necrosis factor receptors p55 and p75 in the plasma of 10 patients with Fulminant Hepatic Failure and 10 healthy control subjects. The capacity of the plasmas at varying dilutions to inhibit the biological activity of 1000 pg/ml of recombinant tumour necrosis factor in a tumour necrosis factor cytotoxicity assay in vitro was also determined. 3. The mean plasma levels of tumour necrosis factor in patients with Fulminant Hepatic Failure (48.4 +/- 10.9 pg/ml) were significantly increased compared with normal control subjects (6.1 +/- 1.04 pg/ml, P < 0.01). Plasma soluble tumour necrosis factor receptors p55 and p75 were also significantly elevated in patients with Fulminant Hepatic Failure (18.16 +/- 9.94 ng/ml and 16.06 +/- 9.93 ng/ml respectively) when compared with normal control subjects (1.28 +/- 0.24 ng/ml and 1.62 +/- 0.91 ng/ml, P < 0.001). 4. Fulminant Hepatic Failure plasma had a much lower capacity to inhibit tumour necrosis factor bioactivity in vitro, with a statistically significant difference between the inhibitory capacity of the Fulminant Hepatic Failure and normal plasma seen at plasma dilutions of 1:5 and 1:20 (P < 0.05). 5. The reduced tumour necrosis factor neutralization capacity observed in Fulminant Hepatic Failure, despite the increased levels of soluble tumour necrosis factor receptors, suggests enhanced susceptibility to the potential deleterious effects of tumour necrosis factor in Fulminant Hepatic Failure.
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Fulminant Hepatic Failure induced by lamotrigine
BMJ, 1995Co-Authors: Alistair J. Makin, Roger Williams, S Fitt, John S DuncanAbstract:Drs A J MAKIN, S FITT, and Professor ROGER WILLIAMS (Institute of Liver Studies, London SE5 9PJ), and Dr J S DUNCAN (National Hospital for Neurology and Neurosurgery, London WC1N 3BG) write: Although lamotrigine causes skin eruptions in 3% of cases,1 to our knowledge, it has not been reported to cause hepatotoxicity. We report a case of Fulminant Hepatic Failure induced by lamotrigine. A 22 year old woman with epilepsy was …
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Extent of the acute phase response in Fulminant Hepatic Failure.
Gut, 1994Co-Authors: S. Izumi, Robin D. Hughes, Peter G. Langley, J. R. B. Pernambuco, Roger WilliamsAbstract:The extent of the acute phase response and the relation between acute phase proteins and cytokines in plasma was investigated in 50 patients with Fulminant Hepatic Failure. On admission, C reactive protein was significantly higher in Fulminant Hepatic Failure (median: 12.4 micrograms/ml, range:0.2-112 micrograms/ml) than in 20 controls (median: 0.8 microgram/ml, range: 0.3-2.9 micrograms/ml, p < 0.001). Serial measurements showed that plasma C reactive protein increased daily after admission until day 5, the end of the study period. alpha 1-Antitrypsin (AAT) (median: 69.1%, range: 27.5-124%) and fibrinogen (median: 1.10 g/l, range: 0-2.82 g/l) were significantly lower in Fulminant Hepatic Failure on admission than in controls (AAT: median: 126%, range: 75.4-149%; fibrinogen: median 2.48 g/l, range: 1.82-3.39 g/l, p < 0.001) and did not change subsequently. Both AAT and fibrinogen were maintained at significantly higher concentrations in survivors than in those who did not. Bacterial infection occurred in 23 patients during the course of Fulminant Hepatic Failure, but did not influence the concentrations of these three proteins. Interleukin 6 was significantly higher in Fulminant Hepatic Failure (median: 21.2 pg/ml, range: 0-871 pg/ml) than in controls (median: 2.4 pg/ml, range: 1.5-8.2 pg/ml, p < 0.001). There was a significant correlation between interleukin 6 and the C reactive protein concentrations in patients with viral hepatitis on admission and in all patients 48 hours later, consistent with other evidence that interleukin 6 stimulates synthesis of this acute phase protein.
Toshikazu Nakamura - One of the best experts on this subject based on the ideXlab platform.
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abrogation of fas induced Fulminant Hepatic Failure in mice by hepatocyte growth factor
Biochemical and Biophysical Research Communications, 1998Co-Authors: Kenichiro Kosai, Shigekazu Nagata, Kunio Matsumoto, Yoshihide Tsujimoto, Toshikazu NakamuraAbstract:Excessive activity of the Fas system in the liver is an essential event and contributor to Fulminant Hepatic Failure, whose prognosis is extremely poor with high mortality due to lack of effective therapy. Administration of agonistic anti-Fas antibody to mice rapidly led to massive liver apoptosis and Fulminant Hepatic Failure. In contrast, administration of human recombinant hepatocyte growth factor (HGF) abrogated Fas-induced massive liver apoptosis and the lethal Hepatic Failure. Addition of anti-Fas antibody to hepatocytes in primary culture induced cell death, but Fas-mediated cell death was potently suppressed by HGF. HGF strongly induced Bcl-xL expression and subsequently blocked Fas-mediated signaling pathway upstream of CPP32 in the liver. These results implicate a potential therapeutic usage of HGF for treatment of Fulminant Hepatic Failure.
Shigekazu Nagata - One of the best experts on this subject based on the ideXlab platform.
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significance of fas antigen mediated apoptosis in human Fulminant Hepatic Failure
The American Journal of Gastroenterology, 2000Co-Authors: Yumiko Kamogawa, Ikuo Ikeda, Katsumi Yamauchi, Shin Yonehara, Shigekazu Nagata, Naoaki HayashiAbstract:OBJECTIVE: The aim of this study was to elucidate the role of apoptosis in human Fulminant Hepatic Failure. We studied the expression of Fas antigen on liver tissues, Fas ligand in lymphocytes, and soluble Fas ligand in patients' serum. METHODS: On finding apoptotic cells in Fulminant Hepatic Failure liver, we first examined them using the TUNEL method. Subsequently, the expression of Fas was studied by immunostaining. Simultaneously, Fas ligand presenting on both liver-infiltrated cells and peripheral lymphocytes was studied by reverse transcription-polymerase chain reaction, and soluble Fas ligand in sera was measured by ELISA. RESULTS: By using the TUNEL method, we first demonstrated that many apoptotic cells existed in Fulminant Hepatic Failure but not in normal ones. Our immunohistochemistry study showed that many hepatocytes in Fulminant Hepatic Failure strongly expressed Fas. In addition, Fas ligand on both liver-infiltrating lymphocytes and peripheral lymphocytes in Fulminant Hepatic Failure patients was detected. The serum level of soluble Fas ligand was significantly increased in Fulminant Hepatic Failure (mean value, 2.91 ng/ml in Fulminant Hepatic Failure [n = 10], 1.62 ng/ml in acute hepatitis [n = 10], and 0.27 ng/ml in healthy controls [n = 10]). Furthermore, this serum level of sFas ligand was significantly associated with prothrombin time both in acute hepatitis and Fulminant Hepatic Failure. CONCLUSIONS: The present results indicate that Fas-mediated apoptosis may be one of the triggers for the induction of Fulminant Hepatic Failure.
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abrogation of fas induced Fulminant Hepatic Failure in mice by hepatocyte growth factor
Biochemical and Biophysical Research Communications, 1998Co-Authors: Kenichiro Kosai, Shigekazu Nagata, Kunio Matsumoto, Yoshihide Tsujimoto, Toshikazu NakamuraAbstract:Excessive activity of the Fas system in the liver is an essential event and contributor to Fulminant Hepatic Failure, whose prognosis is extremely poor with high mortality due to lack of effective therapy. Administration of agonistic anti-Fas antibody to mice rapidly led to massive liver apoptosis and Fulminant Hepatic Failure. In contrast, administration of human recombinant hepatocyte growth factor (HGF) abrogated Fas-induced massive liver apoptosis and the lethal Hepatic Failure. Addition of anti-Fas antibody to hepatocytes in primary culture induced cell death, but Fas-mediated cell death was potently suppressed by HGF. HGF strongly induced Bcl-xL expression and subsequently blocked Fas-mediated signaling pathway upstream of CPP32 in the liver. These results implicate a potential therapeutic usage of HGF for treatment of Fulminant Hepatic Failure.
Kenichiro Kosai - One of the best experts on this subject based on the ideXlab platform.
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abrogation of fas induced Fulminant Hepatic Failure in mice by hepatocyte growth factor
Biochemical and Biophysical Research Communications, 1998Co-Authors: Kenichiro Kosai, Shigekazu Nagata, Kunio Matsumoto, Yoshihide Tsujimoto, Toshikazu NakamuraAbstract:Excessive activity of the Fas system in the liver is an essential event and contributor to Fulminant Hepatic Failure, whose prognosis is extremely poor with high mortality due to lack of effective therapy. Administration of agonistic anti-Fas antibody to mice rapidly led to massive liver apoptosis and Fulminant Hepatic Failure. In contrast, administration of human recombinant hepatocyte growth factor (HGF) abrogated Fas-induced massive liver apoptosis and the lethal Hepatic Failure. Addition of anti-Fas antibody to hepatocytes in primary culture induced cell death, but Fas-mediated cell death was potently suppressed by HGF. HGF strongly induced Bcl-xL expression and subsequently blocked Fas-mediated signaling pathway upstream of CPP32 in the liver. These results implicate a potential therapeutic usage of HGF for treatment of Fulminant Hepatic Failure.
Deirdre A Kelly - One of the best experts on this subject based on the ideXlab platform.
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etiology outcome and prognostic indicators of childhood Fulminant Hepatic Failure in the united kingdom
Journal of Pediatric Gastroenterology and Nutrition, 2005Co-Authors: Patrick Mckiernan, Deirdre A KellyAbstract:ABSTRACTObjective:To study the etiology, outcome and prognostic indicators in children with Fulminant Hepatic Failure in the United Kingdom.Design:Retrospective review of all patients <17 years with Fulminant Hepatic Failure from 1991 to 2000. Fulminant Hepatic Failure was defined as presence of coa
