PubMed Health⌕ Search

Biomedical subjects

William Bernal

Publications and source records attributed to William Bernal.

8 recordsLinked to original sources
PubMed2006

Reduced monocyte HLA-DR expression: a novel biomarker of disease severity and outcome in acetaminophen-induced acute liver failure.

Acute liver failure (ALF) shares striking similarities with septic shock where a decrease in HLA-DR expression on monocytes is associated with disease severity and predicts outcome. We investigated monocyte HLA-DR expression in ALF in relation to inflammatory mediator levels and clinical outcome. Monocyte HLA-DR expression was determined in 50 patients with acetaminophen-induced ALF (AALF) and 20 non-acetaminophen-induced ALF (NAALF). AALF patients were divided into dead/transplanted (AALF-NS, n = 26) and spontaneous survivors (AALF-S, n = 24). Fifty patients with chronic liver disease (CLD) and 50 healthy volunteers served as controls. Monocyte HLA-DR expression was determined by double-color flow-cytometry with monoclonal antibodies detecting HLA-DR and monocyte specific CD14. Serum levels of interleukin (IL) -4, -6, -10, tumor necrosis factor (TNF)-alpha and interferon (IFN)-gamma were concomitantly measured by ELISA. Compared to healthy volunteers (75%) and CLD (67%) monocyte HLA-DR percentage expression was lower in AALF (15%, P < .001) and NAALF (22 %, P < .001). Compared to AALF-S, AALF-NS had lower monocyte HLA-DR % (11% vs. 36%, P < .001) and higher levels of IL-4, IL-6, IL-10 and TNF-alpha (P < .001). HLA-DR percentage negatively correlated with INR, blood lactate, pH and levels of encephalopathy (r = -0.8 to -0.5, P < .01), IL-10 (r = -0.8, P < .0001), TNF-alpha (r = -0.4, P = .02). HLA-DR percentage level <or=15% has a 96% sensitivity and 100% specificity and 98% accuracy in predicting poor prognosis. In conclusion, the strong relationship of monocyte HLA-DR expression with indices of disease severity, mediators of inflammation and outcome indicates a key role for this molecule as a biomarker of disease severity and prognosis.

Acetaminophen↗
PubMed2006

Cell-free artificial liver support: design of appropriate clinical studies.

The clinical use of cell-free liver support devices is dependent upon proof of safety and efficacy in clinical trials. The current published data to support their use is limited in both quantity and quality. In most studies, the methodology is such that the effects of these devices are difficult to establish with certainty. Bias might be introduced by the use of uncontrolled studies, and in randomized controlled trials limited size, poorly matched control groups or medical therapy or the use of clinically inappropriate endpoints might be important. Guidelines are now available to provide a framework for the design and execution of such trials, specifically to minimize the systematic errors that are frequently present and that might result in biased estimates of treatment effects. In the present review, the limitations of current studies are discussed and suggestions made as to the design and conduct of future clinical trials.

Biomedical Research↗
PubMed2004

UK legislation on analgesic packs: before and after study of long term effect on poisonings.

OBJECTIVE: To evaluate the long term effect of legislation limiting the size of packs of analgesics sold over the counter. DESIGN: Before and after study. SETTING: Suicides in England and Wales, data from six liver units in England and Scotland and five general hospitals in England, and UK data on sales of analgesics, between September 1993 and September 2002. DATA SOURCES: Office for National Statistics; six liver units in England and Scotland; monitoring systems in general hospitals in Oxford, Manchester, and Derby; and Intercontinental Medical Statistics Health UK. MAIN OUTCOME MEASURES: Deaths by suicidal overdose with paracetamol, salicylates, or ibuprofen; numbers of patients admitted to liver units, listed for liver transplant, and undergoing transplantations for paracetamol induced hepatotoxicity; non-fatal self poisonings with analgesics and numbers of tablets taken; and sales figures for analgesics. RESULTS: Suicidal deaths from paracetamol and salicylates were reduced by 22% (95% confidence interval 11% to 32%) in the year after the change in legislation on 16 September 1998, and this reduction persisted in the next two years. Liver unit admissions and liver transplants for paracetamol induced hepatotoxicity were reduced by around 30% in the four years after the legislation. Numbers of paracetamol and salicylate tablets in non-fatal overdoses were reduced in the three years after the legislation. Large overdoses were reduced by 20% (9% to 29%) for paracetamol and by 39% (14% to 57%) for salicylates in the second and third years after the legislation. Ibuprofen overdoses increased after the legislation, but with little or no effect on deaths. CONCLUSION: Legislation restricting pack sizes of analgesics in the United Kingdom has been beneficial. A further reduction in pack sizes could prevent more deaths.

Analgesics↗
PubMed2003

Intensive care support therapy.

Patients with small-for-size syndrome (SFSS) and acute liver failure share some important clinical features that are paralleled by common approaches to their intensive care unit management. Both are characterized by a period of acute hepatic insufficiency, with clinical features reflecting the impairment of metabolic and immunologic function that results. The basic principles of management of the two conditions remain essentially the same: to support hepatic regeneration, to anticipate and prevent the development of complications, and to identify patients unlikely to survive early in their clinical course so that retransplantation may be considered. Many treatments are available in the intensive care unit to overcome biochemical and metabolic disturbances in acute liver failure. Optimal pharmacologic management of SFSS complicated by portal hypertension and variceal hemorrhage is currently uncertain. Extracorporeal liver support has several theoretical attractions in the critically ill patient with SFSS, through its ability by removal of hepatotoxins to provide an environment more conducive to hepatic regeneration and recovery, or to support and bridge the patient to transplantation. The molecular adsorbent recycling system has been proposed to remove both water-soluble and protein-bound toxins. This system is particularly attractive in the treatment of SFSS, however, despite its current clinical application, there are presently limited published data to support its use.

Critical Care↗
PubMed2003

Changing patterns of causation and the use of transplantation in the United kingdom.

Acute liver failure (ALF) is a rare condition in the United Kingdom. Comprehensive supportive intensive care of extra-hepatic organ failure and the early recognition of and use of transplantation for those who will not survive form the cornerstone of its management. Over the last 30 years there has been a reduction in the proportion of cases resulting from viral and seronegative hepatitis, and a progressive rise in those resulting from severe acetaminophen-induced hepatotoxicity. The latter cases mostly result from deliberate self-poisoning and formed the major cause of ALF hospital admissions and indication for emergency liver transplantation. The increasing misuse of acetaminophen has paralleled a rise in sales and greater availability of the drug. Introduction of legislation to restrict sales of acetaminophen has been followed by a fall in hospital admissions resulting from self-poisoning, a 20% reduction in deaths, and a 50% fall in the number of patients undergoing emergency liver transplantation. The reduction in acetaminophen-related ALF has been paralleled by an increase in the number of transplants performed in ALF of nonacetaminophen etiologies.

Acetaminophen↗
PubMed2002

Blood lactate as an early predictor of outcome in paracetamol-induced acute liver failure: a cohort study.

BACKGROUND: Although the King's College Hospital (KCH) selection criteria for emergency liver transplantation in paracetamol-induced acute liver failure are widely used, strategies to improve sensitivity and facilitate earlier transplantation are required. We investigated the use of arterial blood lactate measurement for the identification of transplantation candidates. METHODS: In a single-centre study, we measured arterial blood lactate early (median 4 h) and after fluid resuscitation (median 12 h) in patients admitted to a tertiary-referral intensive-care unit. Threshold values that best identified individuals likely to die without transplantation were derived in a retrospective initial sample of 103 patients with paracetamol-induced acute liver failure and applied to a prospective validation sample of 107 patients. Predictive value and speed of identification were compared with those of KCH criteria. FINDINGS: In the initial sample, median lactate was significantly higher in non-surviving patients than in survivors both in the early samples (8.5 [range 1.7--21.0] vs 1.4 [0.53--7.9] mmol/L, p<0.0001) and after fluid resuscitation (5.5 [1.3--18.6] vs 1.3 [0.26--3.2], p<0.0001). Applied to the validation sample, a threshold value of 3.5 mmol/L early after admission had sensitivity 67%, specificity 95%, positive likelihood ratio 13, and negative likelihood ratio 0.35; the corresponding values for a threshold of 3.0 mmol/L after fluid resuscitation were 76%, 97%, 30, and 0.24. Combined early and postresuscitation lactate concentrations had similar predictive ability to KCH criteria but identified non-surviving patients earlier (4 [3--13] vs 10 [3.5--19.5] h, p=0.01). Addition of postresuscitation lactate concentration to KCH criteria increased sensitivity from 76% to 91% and lowered negative likelihood ratio from 0.25 to 0.10. INTERPRETATION: Arterial blood lactate measurement rapidly and accurately identifies patients who will die from paracetamol-induced acute liver failure. Its use could improve the speed and accuracy of selection of appropriate candidates for transplantation.

Acetaminophen↗