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J A Wendon

Publications and source records attributed to J A Wendon.

At least 19 recordsLinked to original sources
PubMed2006

Myeloma associated amyloidosis presenting as subacute liver failure.

Multiple myeloma related amyloidosis is rare and its presentation with subacute liver failure (SALF) has not been reported. A case is described of a 46 year old woman presenting with a six week history of nausea, abdominal pain, and jaundice. Routine tests failed to establish a cause. Computed tomography showed a small volume liver consistent with SALF. Emergency liver transplantation was not undertaken because of the suspicion of underlying malignancy. At necropsy, liver biopsy showed amyloid deposition and bone marrow biopsy showed multiple myeloma. Thus, amyloidosis should be added to the list of potential causes of SALF.

Amyloidosis↗
PubMed2005

Effects of serum from patients with acute liver failure due to paracetamol overdose on human hepatocytes in vitro.

OBJECTIVE: Our goal was to investigate the effects of serum from patients with acute liver failure due to paracetamol (acetaminophen) overdose on the function of human hepatocytes in vitro. METHODS: Freshly isolated human hepatocytes plated on collagen-coated culture plates were, incubated (24 hours 37 degrees C) in medium containing pooled human sera (0%-80%) obtained from normal individuals or from patients with acute liver failure due to paracetamol overdose. The effects of the sera on cell function were assessed using MTT, [14C]-leucine incorporation, and cytochrome P450 (CYP1A1/2) activity assays. RESULTS: The overall cellular metabolic activity was significantly greater at all concentrations after exposure to acute liver failure serum compared to normal serum. There were no significant differences in the decreases produced by pooled acute liver failure and normal sera at concentrations up to 80% on the [14C]-leucine incorporation or CYP1A1/2 activity. CONCLUSION: The overall cell function/activity of human hepatocytes was not impaired in vitro on exposure to serum from patients with acute liver failure due to paracetamol overdose.

Acetaminophen↗
PubMed2005

Liver support.

Explore the source record for details and available documents.

Humans↗
PubMed2001

Temporal changes in insulin sensitivity following the development of acute liver failure secondary to acetaminophen.

Insulin resistance in chronic liver disease (CLD) is well documented. This study investigated whether similar changes occur in acute liver failure (ALF). Patients with ALF (n = 10) were recruited within 72 hours of their peak prothrombin time (range 42-120 seconds). All patients were ventilated for encephalopathy (grade III-IV). Peripheral and endogenous insulin sensitivity were assessed by a hyperinsulinemic euglycemic clamp (Human Actrapid 1.5 mU/min/kg) with an infusion of D-[6,6-(2)H(2)] glucose. The clamp was performed on day 0 and then on day 7 and day 14. During the insulin infusion, the mean total peripheral glucose uptake (area under the curve [AUC]) was 1,422 (SD, 1,253), 2,244 (SD, 1,392), and 4,500 (SD, 1,120) micromol/kg on days 0, 7, and 14, respectively. Significant changes occurred from day 0 to 14 (day 14-day 0: 3,078 [95% CI, 1,798 to 4,359]; P =.001) and day 7 to 14 (day 14-day 7: 2,256 [95% CI, 923 to 3,589]; P =.001). No significant difference in endogenous glucose production was demonstrated over time. Mean peripheral insulin sensitivity altered over time, increasing from 0.09 (SD, 0.09) micromol/kg/min/mU/L on day 0 to 0.24 (SD, 0.16) on day 7 and 0.5 (SD, 0.1) on day 14. Significant changes occurred between days 0, 7, and 14 (day 7-day 0: 0.15 [95% CI, 0.04 to 0.26], P =.006; day 14-day 0: 0.4 [95% CI, 0.28 to 0.5], P =.001; day 14-day 7: 0.2 [95% CI, 0.12 to 0.38], P =.001). This study demonstrates that in ALF, impaired peripheral uptake of glucose occurs, peripheral insulin sensitivity being restored at 2 weeks in subjects who survived.

Acetaminophen↗
PubMed2001

Liver and intestinal lactate metabolism in patients with acute hepatic failure undergoing liver transplantation.

OBJECTIVE: To determine the relative contribution of the gastrointestinal tract and the liver in lactate metabolism in patients with acute liver failure (ALF) and the effect of liver transplantation on this. We hypothesized that the liver and gut are net producers of lactate in ALF and that this is reversed after liver transplantation. SETTING: A university-affiliated specialist liver transplant operating theater. SUBJECTS: Eleven patients with ALF undergoing liver transplantation. MEASUREMENTS AND INTERVENTIONS: After ethical approval, 11 patients with ALF listed for orthotopic hepatic transplantation were studied. Whole blood was analyzed for lactate concentration from radial artery (RA) catheter, portal vein (PV), and hepatic vein (HV) during the dissection phase and was repeated postreperfusion of the liver graft. Gradients across the gut and the liver were calculated to see if there was net production or consumption. RESULTS: HV lactate was significantly higher than arterial (p =.028) in patients with ALF before liver transplantation, suggesting splanchnic production of lactate. Total splanchnic lactate gradient (HV-RA) is positive in ALF. Both the gut (PV-RA) and the liver (HV-PV) were net producers of lactate. After liver transplantation, hepatic venous lactate falls below arterial levels but not significantly. The gradient across the gut (PV-RA) remained positive, but the transhepatic gradient (HV-PV) became significantly negative, showing consumption by the graft (p =.021). The magnitude of lactate consumption after transplantation correlated positively with portal venous lactate concentration (p =.029) and inversely with graft cold ischemic time (p =.007). CONCLUSION: The liver is a net producer of lactate in patients with ALF and an elevated whole blood lactate. After liver transplantation, the graft becomes a consumer of lactate as shown by the negative lactate gradient. The degree of consumption is dependent on portal venous lactate concentration and cold ischemic time.

Female↗
PubMed2001

Perioperative management of liver transplantation patients.

Perioperative care involves many disciplines, each of which contributes in important ways. Changes in liver-transplantation care during the last 40 years can be attributed to the accumulation of improvements, discoveries, and technologic improvements across different disciplines. Here we review some of the articles that were published during the last year that relate to these advances.

Humans↗
PubMed2000

A prospective study of gastric mucosal ischaemia in paracetamol-induced acute liver failure.

OBJECTIVE: To evaluate the time course of changes in the gastric mucosal pH (pHi) and the gastric mucosal to arterial CO2 gap (CO2 gap) following paracetamol-induced acute liver failure and to relate these variables to the severity of illness. DESIGN: Clinical prospective study. SETTING: A liver intensive care unit in a university teaching hospital. PATIENTS: Twenty-three patients with paracetamol-induced acute liver failure. INTERVENTIONS: Gastric tonometer placement. MEASUREMENTS AND MAIN RESULTS: Daily assessment of pHi and CO2 gap, the systemic organ failure assessment (SOFA) score for up to 9 days post-paracetamol ingestion. Both pHi and CO2 gap were within the normal range on entry into the study. The CO2 gap showed increases from the normal range on days 5-7 post-ingestion (P<0.01) and increases from study entry on days 4, 7, and 8 post-ingestion (P< 0.01). The pHi showed decreases from the normal range on days 4, 6, 7 and 9 post-ingestion (P< 0.01) and decreases from study entry on days 4, 5, 7, and 9 post-ingestion (P<0.01). There was no correlation found between pHi, CO2 gap, and the SOFA score. CONCLUSIONS: Paracetamol-induced acute liver failure is associated with increases in the CO2 gap and decreases in pHi between 4 to 9 days post-paracetamol ingestion. This may reflect changes in mesenteric blood flow related to hepatic regeneration. These changes may be in part responsible for some of the morbidity seen with this condition.

Acetaminophen↗
PubMed2000

Subclinical seizure activity and prophylactic phenytoin infusion in acute liver failure: a controlled clinical trial.

Subclinical seizure activity in the patient with encephalopathy and on ventilation with acute liver failure (ALF) is a poorly recognized entity. Its importance lies in the likely exacerbation of cerebral hypoxia and the contribution of such seizure activity to the development of cerebral edema. The aim of the present study was to document the frequency of subclinical seizure activity in a cohort of patients with ALF by using a cerebral function and activity monitor that allows continuous recording of electroencephalogram activity at the bedside and to determine whether the prophylactic administration of the antiepileptic agent phenytoin would reduce its occurrence. Forty-two patients were enrolled in a controlled clinical trial: 20 patients were given phenytoin and 22 acted as controls. Subclinical seizure activity was recorded in 3 and 10 patients, respectively, of the treated and control groups. Pupillary abnormalities indicative of seizure activity and/or raised intracranial pressure (ICP) were also seen less frequently in the phenytoin-treated group compared with the controls (5 and 11 patients, respectively). Autopsy examinations available in 19 patients showed signs of cerebral edema in only 2 (22%) of the phenytoin-treated patients compared with 7 (70%) of the controls (P <.033). Based on these findings, we recommend that patients with ALF, on reaching the stage of grade III or IV encephalopathy, should be routinely monitored for subclinical seizure activity. In this study, prophylaxis with phenytoin reduced the frequency of such seizure activity and its effects, and proved to be safe with the regimen used.

Acute Disease↗
PubMed1999

Temporary extracorporeal liver support for severe acute alcoholic hepatitis using the BioLogic-DT.

Patients with severe acute alcoholic hepatitis develop multiple organ failure which is associated with production of inflammatory cytokines and a poor prognosis. The aim of the present pilot study was to evaluate the effects of the BioLogic-DT sorption-suspension dialyser in patients with severe acute alcoholic hepatitis. Ten patients with encephalopathy (grade II-IV) were entered into the study, 5 received treatment with the BioLogic-DT for 6 hours daily for 3 days and 5 received conventional treatment as controls. The system was biocompatible with no adverse effects on blood pressure or platelet counts, factor V, fibrinogen or antithrombin III. No bleeding episodes were observed even with the use of small doses of heparin. After 3 days, blood ammonia was lower in the BioLogic-DT treated patients than in the controls, although blood lactate was higher. There were slight increases in plasma TNF and IL-8 during treatment over and above the higher levels present initially, possibly as a result of activation of white cells in the extracorporeal circuit. The further development of the BioLogic-DT dialyser with the addition of a plasma treatment module capable of removing cytokines would be worth evaluating in acute alcoholic hepatitis.

Acute Disease↗
PubMed1998

Plasma cytokine levels and coagulation and complement activation during use of the extracorporeal liver assist device in acute liver failure.

Multiple organ failure frequently occurs in patients with acute liver failure, and this has been associated with increased cytokine production. Treatment by hemoperfusion with an extracorporeal liver assist device (ELAD) containing human liver-derived cells was performed in 12 patients with acute liver failure. Over the first 6 h, there were significant increases in plasma tumor necrosis factor alpha (TNFalpha; from 114+/-54 pg/ml [mean+/-SEM] to 236+/-161 pg/ml, p < 0.05) and interleukin (IL)-6 (260+/-121 pg/ml to 445+/-149 pg/ml, p < 0.05) but not in interferon gamma (IFNgamma). A similar pattern with a small peak increase was observed for complement C5b-9 complex. Plasma C-reactive protein (CRP) and thrombin antithrombin (TAT) III complex showed small peaks after 24 h of ELAD hemoperfusion. No such changes were seen in 12 control patients with acute liver failure who were treated with intensive care alone. These transitory effects, without changes in blood pressure, are likely to be due to the contact of the blood with the dialyzer membrane. There was no evidence of the clearance of cytokines by the ELAD.

Adolescent↗
PubMed1997

N-acetylcysteine infusion in viral myocarditis: a case report.

N-acetylcysteine improves survival in established acute liver failure following paracetamol overdose by reducing the incidence of multiorgan failure. These benefits are thought to be related to decreased tissue hypoxia by the enhancement of both oxygen delivery and oxygen extraction. Similar findings have been recorded in critically ill patients from an alternative aetiology. The cardiovascular properties of N-acetylcysteine are to increase stroke volume index, and thus cardiac output, although there is no effect on cardiac output in normal subjects. N-acetylcysteine is known to improve myocardial contraction in a hamster model of chronic myocardial ischaemia, but such effects have not previously been described in humans. We report the beneficial circulatory effect of N-acetylcysteine in a patient with marked left ventricular dysfunction secondary to acute viral myocarditis.

Acetylcysteine↗
PubMed1997

N-acetylcysteine improves indocyanine green extraction and oxygen transport during hepatic dysfunction.

OBJECTIVES: To investigate whether the beneficial systemic hemodynamic effects of N-acetylcysteine, an agent that increases cyclic guanosine monophosphate (cGMP) concentration in fulminant hepatic failure, are present in a range of liver disorders and what concurrent effect this agent has on the hepatic-splanchnic circulation. SETTING: Liver Failure Unit, King's College Hospital, London, UK. PATIENTS: Fifteen patients with hepatic dysfunction who were mechanically ventilated, either after liver transplantation or during an acute or decompensated chronic liver disorder. INTERVENTIONS: Prostacyclin was administered at a continuous infusion rate of 5 ng/kg/min for 60 mins. After a washout period, the hemodynamic effects of this infusion were compared with the effects present during infusion of N-acetylcysteine at 150 mg/kg in 250 mL of 5% dextrose in water over 15 mins and then 50 mg/kg in 250 mL of 5% dextrose for 45 mins at an infusion rate of 62.5 mL/hr. MEASUREMENTS AND MAIN RESULTS: Following N-acetylcysteine infusion, the baseline oxygen delivery (DO2) increased from 667 +/- 154 to 751 +/- 166 (SD) mL/min/m2, and oxygen consumption (VO2) improved in 13 of 15 patients (150 +/- 30 to 169 +/- 25 mL/min/m2) (p< .01). Indocyanine green clearance, as determined by a fiberoptic physiologic monitoring system, also improved in 13 of 15 patients (7.3 +/- 4.2% to 11.8 +/- 4.0% [mean change 100%, 95% confidence interval 9 to 256]) (p = .002). Patients who were defined as responders in relation to systemic hemodynamics (VO2 of >10% from baseline [n = 6; 40%]) had a significantly lower baseline consumption compared with that of nonresponders (133 vs. 162 mL/min/m2, p = .04). No clear relationship between the increments in VO2 and indocyanine green clearance was observed (r2 = .21; p = .08). Prostacyclin resulted in moderate improvements in systemic DO2 (but not VO2) and a nonsignificant increase in indocyanine green clearance. CONCLUSION: N-acetylcysteine increases systemic VO2 in a proportion of patients with a wide variety of hepatic disorders. In addition, N-acetylcysteine elicits an improvement in indocyanine green clearance. These properties may be clinically useful in a range of critical illnesses where systemic or hepatic-splanchnic circulations are compromised.

Acetylcysteine↗
PubMed1997

Use of extracorporeal liver assist device and auxiliary liver transplantation in fulminant hepatic failure.

The case history of a 14-year-old boy with fulminant hepatic failure secondary to non-A, non-B hepatitis who fulfilled selection criteria for orthotopic liver transplantation is described. Two forms of liver support were used (extracorporeal liver assist device and an auxiliary partial orthotopic liver transplantation) to provide additional time to allow spontaneous recovery to occur. During the 66 h of extracorporeal haemoperfusion through the device, haemodynamic stability was maintained along with improvements in serum bilirubin (555 to 381 mumol/l), and international normalized ratio (INR) (3.7 to 2.9). Deterioration in these parameters was observed following cessation of treatment and 10 h later, after a donor liver had become available, an auxiliary transplant was performed. Clinical recovery, though initially slow, was eventually complete, with histopathological and scintigraphic evidence of full liver regeneration at 3 months. Withdrawal of his immunosuppressive drugs began at 6 months and was complete by 14 months after auxiliary transplantation. He has since remained well with normal liver function tests. Temporary liver support may provide additional time for spontaneous recovery of the native liver to occur in selected cases of fulminant hepatic failure, even when criteria are fulfilled for orthotopic liver grafting.

Adolescent↗
PubMed1996

Pilot-controlled trial of the extracorporeal liver assist device in acute liver failure.

The objective of this pilot controlled study was to evaluate the extracorporeal liver assist device (ELAD) in patients with acute liver failure who were judged to still have a significant chance of survival (approximately 50%) and in those who had already fulfilled criteria for transplantation. Twenty-four patients were divided into two groups, 17 with a potentially recoverable lesion (group I) and 7 listed for transplantation (group II), and then randomly allocated to ELAD haemoperfusion or control. The median period of ELAD haemoperfusion was 72 hours (range 3-168 h). Biocompatibility of the device was good, with no acceleration in platelet consumption, and haemodynamic stability was maintained. Two patients were withdrawn from the study because of worsening of preexisting disseminated intravascular coagulation in one case and a hypersensitivity reaction in the other. Deterioration with respect to encephalopathy grade was more frequent in the control patients, 7 of 12 (58%), than in the ELAD-treated patients, 3 of 12 (25%). In group I where survival for the ELAD cases was 7 of 9 (78%), there was a higher than expected survival in the controls, 6 of 8 (75%). For group II cases, survival was 1 of 3 (33%) for the ELAD-treated patients, and 1 of 4 (25%) for the controls. Both of the survivors underwent transplantation. Assessment of additive function for the device revealed an improvement in galactose elimination capacity after 6 hours of haemoperfusion. Based on the results of this pilot-controlled trial, better indices of prognosis will be required, in addition to those used to select for transplantation, if patients at an earlier stage of clinical deterioration are to be included in future studies.

Adolescent↗
PubMed1996

Acute liver damage and ecstasy ingestion.

Eight cases of ecstasy related acute liver damage referred to a specialised liver unit are described. Two patients presented after collapse within six hours of ecstasy ingestion with hyperthermia, hypotension, fitting, and subsequently disseminated intravascular coagulation with rhabdomyolysis together with biochemical evidence of severe hepatic damage. One patient recovered and the other with evidence of hyperacute liver failure was transplanted but subsequently died, histological examination showing widespread microvesicular fatty change. Four patients presented with acute liver failure without hyperthermia. All four fulfilled criteria for transplantation, one died before a donor organ became available, and two died within one month post-transplantation of overwhelming sepsis. Histological examination showed submassive lobular collapse. Two patients presented with abdominal pain and jaundice and recovered over a period of three weeks; histological examination showed a lobular hepatitis with cholestasis. Patients developing jaundice or with evidence of hepatic failure particularly encephalopathy and prolongation of the international normalised ratio, or both, whether or not preceded by hyperthermia, should be referred to a specialised liver unit as liver transplantation probably provides the only chance of recovery.

Adolescent↗
PubMed1996

Effect of ELAD liver support on plasma HGF and TGF-beta 1 in acute liver failure.

The aim of this study was to investigate the effects of treatment with the extracorporeal liver assist device (ELAD) in patients with acute liver failure (ALF) on plasma hepatocyte growth factor (HGF), the most potent growth factor, and transforming growth factor-beta 1 (TGF-beta 1), an inhibitory factor for liver regeneration. Initial plasma HGF, measured by ELISA, was significantly increased in the ALF patients (7.86 +/- SEM 1.76 ng/ml) compared with normal subjects (0.10 +/- 0.02 ng/ml, p < 0.001). After 6 hours of ELAD haemoperfusion, plasma HGF increased further (30.5 +/- 6.19 ng/ml, p < 0.001), with a subsequent decrease towards the initial value by 48 hours. Initial plasma levels of TGF-beta 1 determined by ELISA were significantly increased in the ALF patients (43.4 +/- 5.9 ng/ml) compared with normal subjects (25.1 +/- 2.3 ng/ml, p < 0.01), but there was no change in plasma TGF-beta 1 during the study period in either the ELAD or control ALF group. As HGF is a heparin-binding growth factor and similar changes in HGF were observed during CVVHD, one possible explanation is that heparin administered as anticoagulant for extracorporeal circulation is involved in the effects observed on HGF.

Adolescent↗
PubMed1994

Evaluation of the BioLogic-DT sorbent-suspension dialyser in patients with fulminant hepatic failure.

The BioLogic-DT sorbent suspension dialyser was developed to remove toxic substances from the blood of patients with liver failure. In the present study a randomised controlled trial was carried out in 10 patients with fulminant hepatic failure who had developed grade 4 encephalopathy to evaluate the safety and biocompatibility of the dialyser in such severely ill patients. A total of 18 treatments were performed in 5 patients. Haemodynamic stability was maintained throughout. There was a significant loss of platelets (163 +/- 34 to 101 +/- 13 x 10(9)/l) and decrease in plasma fibrinogen (0.53 +/- 0.09 to 0.31 +/- 0.08 g/l) with a rise in blood activated clotting time (190 +/- 17 to 223 +/- 22 sec)--not seen in the controls--, which was a result of the dialysis being carried out without the use of heparin as anticoagulant. Removal of metabolites by treatment was limited, with no significant effect on blood ammonia level and further developments of the system will be needed for this very sick group of patients.

Adult↗