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Biomedical subjects

Julia Wendon

Publications and source records attributed to Julia Wendon.

At least 19 recordsLinked to original sources
PubMed2006

Results from the International Conference of Experts on Intra-abdominal Hypertension and Abdominal Compartment Syndrome. I. Definitions.

OBJECTIVE: Intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) have been increasingly recognized in the critically ill over the past decade. The variety of definitions proposed has led to confusion and difficulty in comparing one study to another. DESIGN: An international consensus group of critical care specialists convened at the second World Congress on Abdominal Compartment Syndrome to standardize definitions for IAH and ACS based upon the current understanding of the pathophysiology surrounding these two syndromes. METHODS: Prior to the conference the authors developed a blueprint for the various definitions, which was further refined both during and after the conference. The present article serves as the final report of the 2004 International ACS Consensus Definitions Conference and is endorsed by the World Society of Abdominal Compartment Syndrome (WSACS). RESULTS: IAH is redefined as an intra-abdominal pressure (IAP) at or above 12 mmHg. ACS is redefined as an IAP above 20 mmHg with evidence of organ dysfunction/failure. ACS is further classified as either primary, secondary, or recurrent based upon the duration and cause of the IAH-induced organ failure. Standards for IAP monitoring are set forth to facilitate accuracy of IAP measurements from patient to patient. CONCLUSIONS: State-of-the-art definitions for IAH and ACS are proposed based upon current medical evidence as well as expert opinion. The WSACS recommends that these definitions be used for future clinical and basic science research. Specific guidelines and recommendations for clinical management of patients with IAH/ACS are published in a separate review.

Abdomen↗
PubMed2006

Imatinib mesylate as a cause of acute liver failure.

A 46-year-old patient diagnosed with chronic myeloid leukemia in whom cytogenetic and molecular remission had never been achieved was commenced on Imatinib Mesylate (Gleevec, Novartis Pharmaceuticals Corp., East Hanover, NJ). After 18 months of treatment, she developed abnormal liver function tests and subsequently acute liver failure, requiring transfer to the regional liver unit. The patient proceeded to liver transplantation but later died. The explanted liver had histological features of severe hepatic necrosis. This is the first case described of fatal hepatic necrosis in a patient who has have been on long-term imatinib therapy. This may have implications for long-term use of the drug and emphasizes the need for regular monitoring of liver function.

Antineoplastic Agents↗
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

Prevalence of the activating JAK2 tyrosine kinase mutation V617F in the Budd-Chiari syndrome.

BACKGROUND & AIMS: Budd-Chiari Syndrome (BCS) results from obstruction to hepatic venous outflow, with myeloproliferative disorder (MPD) accounting for up to 40% of cases. A number of BCS cases labelled as "idiopathic" do not fulfill the diagnostic criteria for MPD but have features suggestive of a latent form based on hyperplastic bone marrow and erythroid progenitor cell culture; these cases may subsequently develop overt MPD. A clonal mutation in JAK2 tyrosine kinase (JAK2V617F) occurs in a high proportion of patients with MPD and is of use in the characterization of latent MPD in BCS. METHODS: We performed allele-specific polymerase chain reaction to screen for JAK2V617F in subjects with BCS (n = 41) and polycythemia vera (PV) (n = 20) and in hematologically normal controls (n = 27). RESULTS: AK2V617F was detected in 24 of 41 (58.5%) subjects with BCS, 19 of 20 PV controls, and 0 of 27 hematologically normal controls. Mean hemoglobin concentration and hematocrit were significantly higher in patients with JAK2V617F. Bone marrow was hyperplastic in 16 of 41 subjects (12/16 JAK2V617F positive). Nine of 33 (27.3%) showed endogenous erythroid colony formation (7/9 JAK2V617F positive). Eleven of 41 subjects developed overt MPD (8/11 essential thrombocythemia, 3/11 PV) after the diagnosis of BCS (median, 49 months; range, 8-87 months), and in 90.9% of these JAK2V617F was detected. CONCLUSIONS: JAK2V617F occurs in a high proportion of patients with BCS. Latent MPD was missed in a substantial number of our subjects by using standard techniques. Such cases should be screened for JAK2V617F and carefully observed for the subsequent development of overt MPD.

Adolescent↗
PubMed2006

Change in model for end-stage liver disease score on the transplant waiting list predicts survival in patients undergoing liver transplantation.

Allocation of donor livers through the model for end-stage liver disease (MELD) score has resulted in a fall in waiting list deaths in the United States. Change in MELD score (DeltaMELD) whilst awaiting transplant has been suggested as a method of refining organ allocation. Our aims were to analyse the effect of DeltaMELD between listing and transplant, and examine its impact on patient survival, intensive care stay and hospital stay in 402 patients transplanted for chronic liver disease at a single centre. Patients who had a DeltaMELD score of >+1 point were more likely to die in hospital following transplant (P < 0.05) and had a significantly worse 12- and 36-month survival post transplant (P < 0.0001) when compared with patients with DeltaMELD <or=+1 (77.8% vs. 91.9% at 12 months; 72.1% vs. 83.6% at 36 months). This difference persisted even when in-hospital deaths were excluded (P = 0.0148). In a Cox-proportional hazards model, factors associated with reduced survival were DeltaMELD (P = 0.008), and transplant from intensive care (P < 0.001). In conclusion, change in MELD score whilst on the transplant waiting list has a significant effect on survival post-transplant although MELD score at the time of transplant appears to have the most significant effect on resource utilization.

Adult↗
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↗
PubMed2006

Pulmonary artery catheter versus pulse contour analysis: a prospective epidemiological study.

INTRODUCTION: The choice of invasive systemic haemodynamic monitoring in critically ill patients remains controversial as no multicentre comparative clinical data exist. Accordingly, we sought to study and compare the features and outcomes of patients who receive haemodynamic monitoring with either the pulmonary artery catheter (PAC) or pulse contour cardiac output (PiCCO) technology. METHODS: We conducted a prospective multicentre, multinational epidemiological study in a cohort of 331 critically ill patients who received haemodynamic monitoring by PAC or PiCCO according to physician preference in intensive care units (ICUs) of eight hospitals in four countries. We collected data on haemodynamics, demographic features, daily fluid balance, mechanical ventilation days, ICU days, hospital days, and hospital mortality. We statistically compared the two techniques. RESULTS: Three hundred and forty-two catheters (PiCCO 192 and PAC 150) were inserted in 331 patients. On direct comparison, patients with PAC were older (68 versus 64 years of age; p = 0.0037), were given inotropic drugs more frequently (37.3% versus 13%; p < 0.0001), and had a lower cardiac index (2.6 versus 3.2 litres/minute per square meter; p < 0.0001). Mean daily fluid balance was significantly greater during PiCCO monitoring (+659 versus +350 ml/day; p = 0.017) and mechanical ventilation-free days were fewer (12 for PiCCO versus 21 for PAC; p = 0.045). However, after multiple regression analysis, we found no significant effect of monitoring technique on mean daily fluid balance, mechanical ventilation-free days, ICU-free days, or hospital mortality. A secondary multiple logistic regression analysis for hospital mortality which included mean daily fluid balance showed that positive fluid balance was a significant predictor of hospital mortality (odds ratio = 1.0002 for each ml/day; p = 0.0073). CONCLUSION: On direct comparison, the use of PiCCO was associated with a greater positive fluid balance and fewer ventilator-free days. After correction for confounding factors, the choice of monitoring did not influence major outcomes, whereas a positive fluid balance was a significant independent predictor of outcome. Future studies may best be targeted at understanding the effect of pursuing different fluid balance regimens rather than monitoring techniques per se.

Aged↗
PubMed2005

Pharmacokinetics and efficacy of oral versus intravenous mixed-micellar phylloquinone (vitamin K1) in severe acute liver disease.

BACKGROUND/AIMS: In patients with severe acute liver dysfunction, i.v. phylloquinone (vitamin K1) may be given to exclude vitamin K deficiency, rather than impaired hepatic synthesis of coagulation factors alone, as the cause of the coagulopathy. However, there have been no studies of the pharmacokinetics or efficacy of i.v. or oral K1 in such patients. METHODS: 49 adults with severe acute liver disease were randomised double-blind to a single 10 mg dose of i.v. or oral mixed-micellar K(1), or placebo. Serum levels of phylloquinone and undercarboxylated prothrombin (PIVKA-II) were assessed before and after treatment. RESULTS: At admission, 13 patients (27%) had either low serum K1 levels or elevated PIVKA-II concentrations, indicative of subclinical vitamin K deficiency. In the 16 patients who received i.v. K1, there was one (6%) treatment failure (K1 rise <10 ng/ml above baseline), compared with 12 of the 15 (80%) who received oral K1 (P<0.0001). One patient in the placebo group developed overt vitamin K deficiency. CONCLUSIONS: A minority of patients with severe acute liver dysfunction have subclinical vitamin K deficiency at the time of presentation, which is corrected by a single dose of i.v. K1. The intestinal absorption of mixed-micellar K1 is unreliable in adults with severe acute liver dysfunction.

Acute Disease↗
PubMed2005

Use of recombinant activated factor VII for bleeding in pancreatitis: a case series.

OBJECTIVES: To describe the effects of recombinant activated factor VII (rFVIIa) in the treatment of bleeding in a series of patients with acute or chronic pancreatitis. METHODS: Twelve patients (age, 2.5-65 years) with pancreatitis and bleeding were treated with 18.5 to 120 microg/kg of rFVIIa. Eight patients also had sepsis/infection and/or disseminated intravascular coagulation (DIC). The effects of rFVIIa on bleeding, coagulation status, and transfusion requirements were noted. RESULTS: Bleeding stopped in 4 patients, was markedly reduced in 4 patients, was reduced in 3 patients, and was remained unchanged in 1 patient. For most patients with pre- and post-rFVIIa data, coagulation parameters improved and transfusion requirements reduced. No thrombotic adverse events occurred. Seven patients died for reasons considered to be unrelated to rFVIIa treatment. CONCLUSIONS: This case series indicates that rFVIIa may be an effective hemostatic treatment of patients with pancreatitis suffering from massive bleeding. There were no thromboembolic events in any patient, including those with sepsis or DIC.

Adult↗
PubMed2004

The effect of hypertonic sodium chloride on intracranial pressure in patients with acute liver failure.

Acute liver failure (ALF) is a rare condition characterized by the development of encephalopathy in the absence of chronic liver disease. Cerebral edema occurs in up to 80% of patients with Grade IV encephalopathy. In the current prospective randomized controlled clinical trial, we examined the effect of induced hypernatremia on the incidence of intracranial hypertension (IH) in patients with ALF. Thirty patients with ALF and Grade III or IV encephalopathy were randomized. Patients in Group 1 (n = 15) received the normal standard of care. Patients in Group 2 (n = 15) received standard care and hypertonic saline (30%) via infusion to maintain serum sodium levels of 145-155 mmol/L. Intracranial pressure (ICP) was monitored in all patients with a subdural catheter (Camino Systems, San Diego, CA) for up to 72 hours after inclusion. Serum sodium levels became significantly different from the levels observed in the control group at 6 hours (P <.01). Over the first 24 hours, norepinephrine dose increased relative to baseline in the control group (P <.001; 13 patients) but not in the treatment group. ICP decreased significantly relative to baseline over the first 24 hours in the treatment group (P =.003; 13 patients) but not in the control group. The incidence of IH, defined as a sustained increase in ICP to a level of 25 mm Hg or greater, was significantly higher in the control group (P =.04). In conclusion, induction and maintenance of hypernatremia can reduce the incidence and severity of IH in patients presenting with ALF.

Adult↗
PubMed2003

Piperacillin-tazobactam versus ciprofloxacin plus amoxicillin in the treatment of infective episodes after liver transplantation.

An optimum antimicrobial regimen for bacterial infection after orthotopic liver transplantation has not been identified. In this prospective 4 year study of patients undergoing liver transplantation, patients were randomized to receive either piperacillin-tazobactam (112 patient episodes) or ciprofloxacin plus amoxicillin (105 patient episodes) for empirical treatment of infective episodes in the first 3 months after transplant. Metronidazole was added to the ciprofloxacin-amoxicillin regimen where anaerobic infection was suspected. Patient groups were comparable with respect to clinical, biochemical and haematological parameters. At the 72 h primary efficacy end-point, the overall response rate for the intention-to-treat group was 74/112 (66.1%) for piperacillin-tazobactam and 63/105 (60.0%) for ciprofloxacin plus amoxicillin (P=0.399); the corresponding figures for the per-protocol (PP) group were 73/82 (89.0%) (piperacillin-tazobactam) and 61/80 (76.3%) (ciprofloxacin plus amoxicillin) (P=0.038). At the end-of-study assessment, 58.9% of episodes in the piperacillin-tazobactam group had a successful clinical outcome, compared with 50.5% in the ciprofloxacin plus amoxicillin group (P=0.222); the corresponding figures for the PP group were 83.5% (piperacillin-tazobactam) and 68.8% (ciprofloxacin plus amoxicillin) (P=0.038). Staphylococci and aerobic Gram-negative bacilli were the predominant pathogens in both groups. Bacteria resistant to the study drugs were encountered, including methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecium and multiply-resistant Klebsiella spp. Empirical monotherapy with piperacillin-tazobactam is an effective treatment for infective episodes in liver transplant patients.

Adolescent↗
PubMed2003

The effects of supraphysiological doses of corticosteroids in hypotensive liver failure.

BACKGROUND: In septic shock, supraphysiological doses of corticosteroids reduce norepinephrine requirements. We reviewed our experience of this treatment in hypotensive liver failure. METHODS: We retrospectively analysed 20 patients with liver failure who were treated with supraphysiological doses of hydrocortisone because of norepinephrine dependence. We compared their norepinephrine requirements, outcome, microbiology and incidence of gastrointestinal bleeding to an historical control group treated with norepinephrine but not corticosteroids. RESULTS: After 48 h of steroid treatment, the median norepinephrine dose was reduced (0.14 microg/kg/min to 0.08 microg/kg/min; P < 0.05) while the blood pressure over the same period of time did not change significantly (67.3 mm Hg to 70 mm Hg). Duration of ITU stay was longer in the steroid treated group (13.5 days vs 3 days; P < 0.05) but survival was similar in both groups. There were 23 episodes of positive bacterial cultures after norepinephrine was started in the steroid treated group, compared with 18 episodes in the control group. More of the positive cultures were due to resistant organisms in the steroid treated group (65% vs 17% in the control group; P < 0.002). There was no significant bleeding due to gastrointestinal inflammation in either group. CONCLUSIONS: Supraphysiological doses of corticosteroids reduce norepinephrine requirements in hypotensive liver failure. They do not improve survival but may extend time to find a suitable donor in those awaiting urgent liver transplantation.

Adrenal Cortex Hormones↗
PubMed2002

Acute sickle cell hepatopathy represents a potential contraindication for percutaneous liver biopsy.

After several complications following percutaneous liver biopsy in patients with sickle cell disease, we reviewed our experience. We examined 14 patients with sickle cell disease who underwent a percutaneous liver biopsy. Clinicopathologic findings were correlated with outcome. Of 14 patients, 5 (36%) suffered serious hemorrhage; 4 died (80%; 28% of all patients). None of the 9 patients without biopsy complications was in an acute sickling crisis at the time of biopsy; 4 of 5 patients with complications were in acute sickling crisis. Of the 5 patients with complications, 4 underwent biopsy for an emergency indication. Chronic venous outflow obstruction, marked hepatic sequestration of erythrocytes, and sinusoidal dilatation were strongly associated with complications. Data obtained by biopsy in group 1 were not of substantial value in clinical management, in contrast to group 2 (8/9; 89%). Acute hepatic disease complicating sickle cell anemia represents a newly identified contraindication to percutaneous liver biopsy.

Acute Disease↗