Biomedical subjects

J Wendon

Publications and source records attributed to J Wendon.

At least 19 recordsLinked to original sources

PubMed2003

Timing and aetiology of bacterial infections in a liver intensive care unit.

We undertook a prospective study of 887 consecutive adult patients admitted over an 11 year period to a liver intensive care unit. One or more bacterial infections occurred in 335 (37.8%) patients. Gram-positive cocci predominated. In relation to the date of admission these infections occurred in a statistically significant sequence. Streptococci infections were earliest (median time to infection two days), followed by Staphylococcus aureus (three days), coagulase-negative staphylococci (six days) and enterococci (eight days). Escherichia coli infections occurred earlier than those due to klebsiella-enterobacter (two vs seven days; P = 0.0001) and, overall, Enterobacteriaceae earlier than non-fermentative Gram-negatives (four vs. eight days; P = 0.0081). This study contributes to the management of high-dependency patients by confirming statistically the timing and sequence of infecting bacteria in patients with acute liver failure.

Adult↗

PubMed2002

Severe hepatic dysfunction in pregnancy.

Acute liver disease in pregnancy may have fatal consequences. Pre-eclampsia, HELLP syndrome and acute fatty liver of pregnancy form a spectrum of disease that range from mild symptoms to severe life-threatening multi-organ dysfunction. Early recognition of signs and prognostic indicators may enable prompt referral to specialist centres providing the multidisciplinary support required to reduce maternal and perinatal morbidity and mortality. We review the common causes of acute hepatic failure associated with pregnancy, and current management practices.

Fatty Liver↗

PubMed2001

Liver transplantation in adults coinfected with HIV.

OBJECTIVE: To report our experience of prospectively identifying and transplanting livers into HIV-positive patients. DESIGN: Liver transplantation in HIV-positive patients remains controversial. The finding of HIV is usually considered a contraindication to any form of transplantation. Previously reported cases are few and refer to patients who tested HIV positive after they had their liver transplantations or who seroconverted in the posttransplantation period. This is, to our knowledge, the only report of patients who were known to be HIV positive at the time of decision for listing for transplantation. METHODS: The medical records of five HIV-positive patients who received liver transplants in King's College Hospital, London, during a 5-year period (January 1995-December 1999) were reviewed. All five were known to be HIV positive at the time of listing for liver replacement. Three of them had end-stage liver disease due to hepatitis C (two of them had underlying Hemophilia A) while the other two had acute liver failure, one due to hepatitis B infection and one due to nonA-nonB-nonC hepatitis. In all but one patient the HIV infection had been asymptomatic. RESULTS: All patients survived the immediate posttransplantation period, but the three patients with hepatitis C died of complications of recurrent hepatitis C between 6 and 25 months posttransplantation. The other two patients are currently alive 4 and 34 months posttransplantation with good graft function and without complications from their HIV infection. CONCLUSION: The early outcome of liver transplantation in HIV seropositive patients can be good, and patients should not be excluded from transplantation if their liver disease determines their prognosis. More effective antiviral therapy for hepatitis C given posttransplantation, and for hepatitis B reinfection, should improve the longer-term outcome of HIV patients with end-stage liver disease due to hepatitis.

Adolescent↗

PubMed2001

Acute liver failure as the initial manifestation of acute leukaemia.

BACKGROUND/AIMS: Haematological malignancies seldom cause clinically significant liver disease. Acute liver failure as the initial manifestation of acute leukaemia is very rare and carries a very poor prognosis. METHODS/RESULTS: Three cases of acute liver failure secondary to acute leukaemia are described. Each case presented initially as acute liver failure of uncertain cause. Specific treatment for the leukaemia was instituted; however, all three patients died as a consequence of the liver failure. We describe the clinical course and relevant investigations of these patients and discuss possible mechanisms of acute liver failure in this setting. CONCLUSION: Acute leukaemia presenting as acute liver failure has a very poor prognosis. Although a rare cause of acute liver failure, it should be considered in any patient presenting with acute liver failure with prodromal symptoms and a raised peripheral white cell count, lactate dehydrogenase and uric acid.

Acute Disease↗

PubMed2001

Measurement of twitch transdiaphragmatic, esophageal, and endotracheal tube pressure with bilateral anterolateral magnetic phrenic nerve stimulation in patients in the intensive care unit.

OBJECTIVE: In the critically ill, respiratory muscle strength usually has been assessed by measuring maximum inspiratory pressure. The maneuver is volitional, and results can be unreliable. The nonvolitional technique of bilateral anterolateral magnetic stimulation of the phrenic nerves, producing twitch transdiaphragmatic pressure, has been successful in normal subjects and ambulatory patients. In this study we used the technique in the intensive care unit and explored the measurement of twitch endotracheal tube pressure as a less invasive technique to assess diaphragmatic contractility. DESIGN: Clinical study to quantify diaphragm strength in the intensive care unit. SETTING: Patients from three London teaching hospital intensive care units and high-dependency units. PATIENTS: Forty-one intensive care patients were recruited. Of these, 33 (20 men, 13 women) were studied. INTERVENTIONS: Esophageal and gastric balloon catheters were passed through the anaesthetized nose, and an endotracheal tube occlusion device was placed in the ventilation circuit, next to the endotracheal tube. Two 43-mm magnetic coils were placed anteriorly on the patient's neck, and the phrenic nerves were stimulated magnetically. MEASUREMENTS AND MAIN RESULTS: On phrenic nerve stimulation, twitch gastric pressure, twitch esophageal pressure, twitch transdiaphragmatic pressure, and twitch endotracheal tube pressure were measured. Forty-one consecutive patients consented to take part in the study, and twitch pressure data were obtained in 33 of these. Mean transdiaphragmatic pressure was 10.7 cm H2O, mean twitch esophageal pressure was 6.7 cm H2O, and mean twitch endotracheal tube pressure was 6.7 cm H2O. The mean difference between twitch esophageal pressure and twitch endotracheal tube pressure was 0.02 cm H2O. Correlation of the means of twitch endotracheal tube pressure to twitch esophageal pressure was 0.93, and that for twitch endotracheal tube pressure to transdiaphragmatic pressure was 0.78. CONCLUSIONS: Transdiaphragmatic pressure can be measured in the critically ill to give a nonvolitional assessment of diaphragm contractility, but not all patients can be studied. At present, the relationship of twitch endotracheal tube pressure to transdiaphragmatic pressure is too variable to reliably represent a less invasive measure of diaphragm strength.

Adult↗

PubMed2000

The systemic inflammatory response syndrome in acute liver failure.

The systemic inflammatory response syndrome (SIRS) in acute liver failure (ALF), in which infection is common, has not been studied. In this study, SIRS components were recorded on admission and during episodes of infection, in 887 ALF patients admitted to a single center during an 11-year period. Overall, 504 (56.8%) patients manifested a SIRS during their illness, with a maximum of 1, 2, and 3 concurrent SIRS components in 166, 238, and 100 patients, respectively. In 353 (39.8%) patients who did not become infected, a SIRS on admission was associated with a more critical illness, subsequent worsening of encephalopathy, and death. Infected patients more often developed a SIRS and one of greater magnitude. The magnitude of the SIRS in 273 patients with bacterial infection correlated with mortality, being 16.7%, 28.4%, 41.2%, and 64.7% in patients with 0, 1, 2, and 3 maximum concurrent SIRS components, respectively. Similar correlations with mortality were seen for SIRS associated with fungal infection, bacteremia, and bacterial chest infection. Fifty-nine percent of patients with severe sepsis died, as did 98% of those with septic shock. A significant association was found between progressive encephalopathy and infection. Infected patients with progressive encephalopathy manifested more SIRS components than other infected patients. For patients with a SIRS, the proportions of infected and noninfected patients manifesting worsening encephalopathy were similar. In ALF, the SIRS, whether or not precipitated by infection, appears to be implicated in the progression of encephalopathy, reducing the chances of transplantation and conferring a poorer prognosis.

Acetaminophen↗

PubMed2000

Acute liver failure.

Worldwide, viral infection is responsible for the majority of cases of acute liver failure, and the presence of co-existing chronic viral hepatitis may increase its severity. The newly described hepatotrophic viruses, hepatitis G virus and transfusion-transmitted virus, are unlikely to be major aetiological agents. In the USA and western Europe drug-induced hepatotoxicity is the most common cause, and most frequently results from acetaminophen. Hepatotoxicity caused by Ecstasy is increasingly important, particularly in young adults. Hepatic encephalopathy and cerebral oedema remain important and life-threatening complications, and their pathogenesis is not completely understood. The effects of the cerebral metabolism of the high levels of ammonia that circulate in hepatic failure appear to be important. Induced hypothermia is a promising modality of treatment for refractory cerebral oedema, but the only form of treatment known to improve survival is emergency liver transplantation. Living donor and auxiliary liver transplantation are likely to improve survival rates further and reduce the number of patients requiring long-term post-transplant immunosuppression.

Journal Article↗

PubMed2000

Administering granulocyte colony-stimulating factor to acute liver failure patients corrects neutrophil defects.

OBJECTIVES: Neutrophil function is defective in acute liver failure (ALF) and the in vitro ability of granulocyte colony-stimulating factor (G-CSF) to reverse these defects has been reported. The effects of administering G-CSF to ALF patients are presented in this study. DESIGN: This was a prospective, phase I/II, open label, study. SETTING: The liver intensive therapy unit at King's College Hospital, London. PARTICIPANTS: Sequential patients admitted with acute liver failure due to acetaminophen overdose. INTERVENTIONS: G-CSF was given to four groups (each n = 6) of ALF patients as a daily infusion at 25, 50, 100 or 150 microg/m2. A control group of eight patients did not receive G-CSF. MAIN OUTCOME MEASURES: Neutrophil phagocytosis and killing of Staphylococcus aureus and superoxide release before G-CSF administration and at 24 and 96 h thereafter. RESULTS: Neutrophils from patients receiving 50, 100 or 150 microg/m2 G-CSF, but not from control patients or those receiving 25 microg/m2, showed significantly increased phagocytosis and killing at 96 h. Doses of 50 or 150 microg/m2 G-CSF resulted in increased superoxide production at 96 h. No patients discontinued treatment as a consequence of side effects related to G-CSF administration. CONCLUSIONS: G-CSF administration is a safe and effective means of reversing the neutrophil defects of ALF, and may have a role in the prevention and treatment of infection in these patients. A dose of 50 microg/m2/day is as effective as higher doses and was associated with fewer side effects.

Adolescent↗

PubMed2000

In vitro pentamer formation as a biomarker of tacrolimus-related immunosuppressive activity after liver transplantation.

Therapeutic drug monitoring of tacrolimus (FK) is widely performed to assist adjustments of drug dosage but may be an inadequate surrogate of the immunosuppression induced. The aim of this investigation was to develop an alternative method for measuring FK-related immunosuppressive activity in blood samples from liver transplant recipients. A pentamer formation assay (PFA) was devised based on the attachment of the 12 kDa FK-binding protein (FKBP12) to microtitre plates in the presence of calcineurin, calmodulin, Ca++ and FK. Pentamer formation could be detected at FK concentrations > or = 0.2 microg/l by optimising assay conditions, particularly by including Ca++ (0.5 mM) only during the formation of the pentameric complex. Three methods (blood lysis, proteolytic digestion and use of commercial solutions used in a microparticle enzyme immunoassay (MEIA) technique) were incompatible with PFA measurements after extracting immunosuppressive FK-related material from patients' blood samples. However, therapeutic amounts of FK-related material could be quantified by the PFA assay after extraction of blood samples with methanol. There was a moderate correlation (r = 0.689) of FK equivalents assayed by PFA with results using MEIA in 56 blood samples from 14 liver graft recipients, but no obvious relationship of results to variables reflecting their clinical status.

Biomarkers↗

PubMed1999

Acute liver failure; clinical features and management.

Acute liver failure (ALF) is uncommon and may be associated with a high mortality rate. Its aetiology shows considerable geographical variation, with viral hepatitis the most common worldwide, whilst acetaminophen (paracetamol) induced hepatotoxicity forms the most common precipitant in many developed countries. Its management requires meticulous intensive care and the effective management of haemodynamic, septic and cerebral complications. The early identification of patients unlikely to survive without emergency liver transplantation is important to maximize the possibility of an available graft. Survival in those patients who undergo transplantation may be in excess of 75%.

Acetaminophen↗

PubMed1999

The value of serial Doppler ultrasound as a predictor of clinical outcome and the need for transplantation in fulminant and severe acute liver failure.

The aim of this study was to document the changes in Doppler ultrasound variables of the hepatic artery and portal vein in fulminant and severe acute liver failure, and to assess their prognostic significance. 18 adult patients with fulminant and severe acute liver failure underwent serial Doppler sonography, in the early stages after presentation. 12 hourly measurements of hepatic artery resistance index (HARI), spleen length, portal vein cross-sectional area, time average velocity (TAV) and flow volume were performed. Mean HARI (p = 0.03) and mean maximum HARI (p = 0.03) were significantly higher in those who fulfilled criteria for liver transplantation. Increased portal vein flow was demonstrated, although the difference between the groups was not significant. A significant increase in portal vein cross-sectional area (p < 0.02) and spleen length (p < 0.02) was demonstrated. In summary, an increase in portal blood flow to the damaged liver has been demonstrated. The mean HARI is significantly higher in patients who fulfil transplant criteria and may possibly be used as an indicator of poorer prognosis and the need for liver transplantation in acute severe and fulminant liver failure.

Adolescent↗

PubMed1998

Hemophagocytosis: a potential complication in small bowel transplantation.

BACKGROUND: Acquired hemophagocytosis is a histiocytic proliferation associated with phagocytosis of the hemopoietic elements resulting in fever, profound pancytopenia, hepatosplenomegaly, lymphadenopathy, and coagulopathy. Acquired hemophagocytic syndrome is a specific entity that can be differentiated from malignant histiocytosis and familial hemophagocytosis. It has been associated with a variety of disorders, including immunodeficiency, infection, hemopathies, cancer, and autoimmune diseases, as well as with the period following solid organ and bone marrow transplantation. METHODS: We describe a case of a fatal outcome, due to hemophagocytosis, after small bowel transplantation in a patient with systemic lupus erythematosus. RESULTS: Hemophagocytosis secondary to systemic lupus erythematosus has been reported to have a better response to steroid therapy than that associated with infection. In this case, the association of an autoimmune disease, high levels of immunosuppression, and posttransplant sepsis may have triggered the onset of hemophagocytosis. CONCLUSION: It is suggested that patients with systemic lupus erythematosus may represent a high-risk group for developing hemophagocytosis after small bowel transplantation.

Fatal Outcome↗

PubMed1998

Use and outcome of liver transplantation in acetaminophen-induced acute liver failure.

Once defined clinical criteria are fulfilled in acetaminophen-induced hepatotoxicity, prognosis without orthotopic liver transplantation (OLT) may be very poor. In the present study, we examined the application and outcome of OLT in 548 patients admitted to a single center between 1990 and 1996. Four hundred twenty-four (77%) of the patients studied did not fulfill transplantation criteria, and 396 of these (93%) survived. The majority of the 28 nonsurvivors (7%) in this group fulfilled two of three combined criteria, and the finding of a high APACHE III score could be used as an indicator for the need for OLT. Of the 56 patients (45%) not listed, in only a small proportion was this caused by psychiatric reasons, and in the majority, it was a consequence of the rapid development of multiple organ failure and cerebral edema. This also applied to 24 (35%) of the 68 listed patients in whom the rapidity of clinical deterioration, reflected in increasing APACHE III scores, was such that even with the prompt availability of donor organs, OLT was not possible. In the final event, only 44 (35%) of those who fulfilled criteria underwent OLT, of whom 33 (75%) survived to leave the hospital. Survival was greatest in those receiving unreduced grafts, and markers of early graft function differed significantly between survivors and nonsurvivors. Liver transplantation is an effective treatment in a relatively small number of patients with acetaminophen-induced hepatotoxicity, and for a substantial proportion, transplantation was never an option because of the rapidity of clinical deterioration. APACHE III scoring may be of value in decision making and in better defining patients in clinical trials.

Acetaminophen↗

PubMed1998

Tumor necrosis factor genomic polymorphism and outcome of acetaminophen (paracetamol)-induced acute liver failure.

BACKGROUND/AIMS: High levels of tumor necrosis factor-alpha are associated with an increased risk of severe encephalopathy in acute liver failure, and experimental studies suggest that tumor necrosis factor-alpha plays a role in the development of acetaminophen (paracetamol)-induced liver injury and associated multiple organ failure. Inter-individual variations in the production of tumor necrosis factor-alpha have been linked to genomic polymorphisms within the tumor necrosis factor-alpha locus. This study examined whether specific tumor necrosis factor polymorphisms are associated with variations in the severity of clinical features in acetaminophen-induced acute liver failure. METHODS: Genotypes at the -308 tumor necrosis factor A and tumor necrosis factor B Nco1 polymorphic sites were determined in 97 patients with severe acetaminophen-induced hepatotoxicity and 109 controls, using polymerase chain reaction and restriction fragment length polymorphism. The relationship between liver injury, multiple organ failure and encephalopathy, determined retrospectively from clinical notes and genotype, was examined. RESULTS: No significant association was found between either tumor necrosis factor A or B genotype and parameters for multiple organ failure or liver injury. The tumor necrosis factor B1B1 genotype was significantly under-represented in those patients developing severe encephalopathy (p=0.03) and a multivariate logistic regression analysis confirmed the influence of tumor necrosis factor B genotype (p<0.01). The association was independent of the HLA class II allele DRB1*03, which is closely linked to the TNFB locus. CONCLUSIONS: The development of acute liver failure is unlikely to be primarily sepsis driven. However, the apparent protective effect of the tumor necrosis factor B1B1 genotype on the development of severe encephalopathy may be related to the effects of this genotype on tumor necrosis factor-alpha production in sepsis.

APACHE↗

PubMed1998

Earlier identification of patients at risk from acetaminophen-induced acute liver failure.

OBJECTIVE: To determine whether the Acute Physiology and Chronic Health Evaluation (APACHE) II system for the measurement of severity of illness is able to provide an accurate risk of hospital death in patients with acetaminophen-induced acute liver failure or identify those patients needing transfer for possible hepatic transplantation. DESIGN: Data for admission (first 24 hrs) APACHE II scores and King's criteria for urgent transplantation were collected prospectively to compare the APACHE II system and the King's criteria for the prediction of death or need for transplantation. SETTING: A nine-bed specialist liver failure unit (LFU). PATIENTS: One hundred two consecutive patients admitted to the LFU with acetaminophen self-poisoning and a prolonged prothrombin time were studied. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: An APACHE II score of > 15 points was associated with a high mortality (13/20 patients, five of whom survived following hepatic transplantation). There was no relation between APACHE II risk and outcome (mean APACHE II risk of death 0.8%, actual hospital mortality 16%). An APACHE II score of > 15 had a similar power of prediction of death as the King's criteria (sensitivity 82% and 65%, respectively; specificity 98% and 99%, respectively), when considering those patients who were transplanted as "deaths." An APACHE II score of > 15 was able to identify four more patients than the King's criteria on the first day of admission to the LFU. CONCLUSIONS: The crude admission APACHE II score correlated well with mortality in patients with acetaminophen-induced acute liver failure. However, the calculated APACHE II risk of death, using the original drug overdose coefficient, was poorly calibrated. Since specialist liver scores are unfamiliar in the general intensive care setting, the use of an APACHE II score might earlier identify more patients at risk of needing a liver transplant, and hence, expedite appropriate transfer to a specialist liver unit.

APACHE↗

PubMed1998

Acute liver failure secondary to hepatic infiltration: a single centre experience of 18 cases.

BACKGROUND: Acute liver failure (ALF) secondary to malignant infiltration of the liver is rare and is diagnosed often only after death. AIMS: To determine diagnostic factors and particular clinical patterns of illness. METHODS: Review of case notes from all patients with ALF secondary to hepatic infiltration admitted to this unit over an 18 year period (1978-1995). RESULTS: From a total of 4020 admissions, 18 patients were identified with ALF attributable to hepatic infiltration. Mean age was 40.7 years. Aetiology was non-Hodgkin's lymphoma in nine patients, Hodgkin's disease in three, infiltrative metastatic carcinoma in four, and haemophagocytosis with no precipitant cause in two cases. Prodromal symptoms were non-specific, but occurred at least two to four weeks before onset of ALF, making the presence of such symptoms of value in differential diagnosis of the cause of ALF. Clinical examination and investigations were unhelpful in distinguishing these cases from more usual causes of ALF. Usually, the clinical course was of rapid deterioration and death from multiorgan failure, and only one patient survived. Diagnosis was made during life in 15 patients. Histology showed evidence of widespread hepatocellular necrosis, with diffuse infiltration by tumour cells rather than focal cellular aggregation. CONCLUSIONS: Only with accurate histological diagnosis from liver biopsy and institution of specific therapy early in the management of such patients will the best chance of recovery be achieved. In every case of ALF with prodromal symptoms or abnormal imaging, hepatic histology should be obtained by liver biopsy as soon as possible to diagnose infiltrative hepatic disease.

Adolescent↗

PubMed1998

Halothane-induced acute liver failure: continuing occurrence and use of liver transplantation.

BACKGROUND/AIMS: This study was aimed at determining if the frequency and pattern of acute liver failure (ALF) following halothane anaesthesia had decreased during the last 11 years in comparison with a previous series of 48 patients referred between 1965 and 1984 and whether clinical outcome had been altered by the introduction of liver transplantation. METHODS: Between January 1985 and December 1995, all patients with halothane-induced ALF admitted to the Liver Failure Unit at King's College Hospital were identified. Four other European liver transplant centres with a known interest in acute liver failure also provided data. RESULTS: Of the 18 patients admitted, the clinical data were complete in 15. Ten of these patients had at least one previous halothane anaesthesia with documented clinical complications following the earlier exposure in six. Four patients had been re-exposed to halothane within 1 month of the penultimate halothane anaesthesia. Of the 15 patients four survived with medical management alone and 11 patients fulfilled transplant criteria. Four of the latter group were not listed because of rapidly deteriorating medical state and died, and of the seven patients who were listed, three died without a liver becoming available and four were transplanted, one of whom survived. No patient who had grade 4 encephalopathy and a prothrombin time > 50 s survived without a transplant. The survey of the other European liver centres recorded a total of 19 patients with halothane-induced ALF including three cases reported in the literature. Of those, 13 patients had been transplanted with nine survivors. CONCLUSION: Cases of halothane-induced acute liver failure still occur, albeit at a lower frequency than previously, and the Committee on Safety of Medicines guidelines are not being followed. The results of transplantation in these patients are encouraging.

Adult↗

PubMed1997

Maternal and perinatal outcome in severe pregnancy-related liver disease.

Acute fatty liver of pregnancy (AFLP) and the syndrome of hemolysis, elevated liver enzyme levels, and low platelet count (HELLP) are rare but major disorders of the third trimester of pregnancy. Over a 10-year period, 46 women (median age, 30 years; range, 17-41 years) developed hepatic dysfunction severe enough to require transfer to our Liver Failure Unit. Three quarters of the women were nulliparous, and 5 had twin pregnancies; the median gestational age was 35 weeks (range, 24-40 weeks). At admission, 32 patients (70%) were preeclamptic and 21 (46%) were encephalopathic and/or ventilated. Thirty-two patients (70%) had clinical features and laboratory values consistent with AFLP, and 7 (15%) had HELLP syndrome. One patient had preeclamptic liver rupture requiring liver transplantation. In 6 other patients, causes of severe liver dysfunction unrelated to pregnancy were found. Infectious complications occurred in 17 of the patients with AFLP (53%) and in 2 of those with HELLP syndrome (29%). Major intra-abdominal bleeding occurred in 12 women (10 with AFLP), 9 of whom required laparotomies for clot evacuation. Four patients with AFLP (12.5%) had a fatal outcome, with a corresponding perinatal mortality rate of 9%. There were no maternal or perinatal deaths associated with HELLP syndrome. In contrast to results of many previous studies, the results of this large series suggest a relatively favorable maternal and perinatal outcome in severe AFLP and HELLP syndrome. Further improvements in outcome are likely to be achieved through the prevention of the bleeding and infectious complications associated with these disorders.

Adolescent↗