PubMed Health⌕ Search

Biomedical subjects

P Angus

Publications and source records attributed to P Angus.

At least 19 recordsLinked to original sources
PubMed2006

Acid-base balance during continuous veno-venous hemofiltration: the impact of severe hepatic failure.

BACKGROUND: Continuous renal replacement therapy (CRRT) affects acid-base balance but the influence of severe hepatic failure (SHF) on this effect is unknown. AIM: To assess the effect of SHF on acid-base balance in patients receiving CVVH. DESIGN: Retrospective laboratory investigation. SUBJECTS: Forty patients with SHF and acute renal failure (ARF) treated with CVVH and 42 critically ill patients with severe ARF but no liver disease also treated with CVVH (controls). INTERVENTION: Retrieval of clinical and laboratory data from prospective unit and laboratory databases. METHODS: Quantitative acid-base status assessment using the Stewart-Figge methodology. Comparison of findings between the two groups. RESULTS: Although CVVH had a major effect on acid base balance in both groups, patients with SHF had a higher mean lactate concentrations (4.8 vs. 3.1 mmol/L; p<0.0005), a greater base deficit compared to controls (-1 vs. 4.1 mEq/L; p<0.0001) and a lower PaCO 2 tension (36.8 vs. 42.5 mmHg; p<0.0001), despite the use of bicarbonate replacement fluid. The acidifying effect of hyperlactatemia was slightly worsened by an increased strong ion gap (9.3 vs. 4.9 mEq/L; p<0.0001). It was, however, attenuated by an increased strong ion difference apparent (SIDa) (43.6 vs. 41.9 mEq/L; p<0.05) secondary to hypochloremia (96 vs. 100 mmol/L; p<0.0001) and by hypoalbuminemia, although hypoalbuminemia in SHF patients (26 vs. 23; p<0.005) was less pronounced than in controls. CONCLUSION: The use of CVVH does not fully correct the independent acidifying effect of liver failure on acid-base status. Increased lactate and strong ion gap values maintain a persistent base deficit despite the alkalinizing effects of hypoalbuminemia and hypochloremia. The correction of acidosis in SHF patients may require more intensive CVVH.

Acid-Base Equilibrium↗
PubMed2004

Clinical emergence of entecavir-resistant hepatitis B virus requires additional substitutions in virus already resistant to Lamivudine.

Entecavir (ETV) exhibits potent antiviral activity in patients chronically infected with wild-type or lamivudine (3TC)-resistant (3TC(r)) hepatitis B virus (HBV). Among the patients treated in phase II ETV clinical trials, two patients for whom previous therapies had failed exhibited virologic breakthrough while on ETV. Isolates from these patients (arbitrarily designated patients A and B) were analyzed genotypically for emergent substitutions in HBV reverse transcriptase (RT) and phenotypically for reduced susceptibility in cultures and in HBV polymerase assays. After 54 weeks of 3TC therapy, patient A (AI463901-A) received 0.5 mg of ETV for 52 weeks followed by a combination of ETV and 100 mg of 3TC for 89 weeks. Viral rebound occurred at 133 weeks after ETV was started. The 3TC(r) RT substitutions rtV173L, rtL180M, and rtM204V were present at study entry, and the additional substitutions rtI169T and rtM250V emerged during ETV-3TC combination treatment. Reduced ETV susceptibility in vitro required the rtM250V substitution in addition to the 3TC(r) substitutions. For liver transplant patient B (AI463015-B), previous famciclovir, ganciclovir, foscarnet, and 3TC therapies had failed, and RT changes rtS78S/T, rtV173L, rtL180M, rtT184S, and rtM204V were present at study entry. Viral rebound occurred after 76 weeks of therapy with ETV at 1.0 mg, with the emergence of rtT184G, rtI169T, and rtS202I substitutions within the preexisting 3TC(r) background. Reduced susceptibility in vitro was highest when both the rtT184G and the rtS202I changes were combined with the 3TC(r) substitutions. In summary, infrequent ETV resistance can emerge during prolonged therapy, with selection of additional RT substitutions within a 3TC(r) HBV background, leading to reduced ETV susceptibility and treatment failure.

Adult↗
PubMed2004

Kidney failure associated with liver transplantation or liver failure: the impact of continuous veno-venous hemofiltration.

BACKGROUND AND AIMS: The short-term outcome of critically ill patients with kidney failure combined with severe liver failure or orthotopic liver transplantation (OLTx) is poor. We sought to test the hypothesis that, with the exclusive use of continuous veno-venous hemofilration (CVVH) with minimal heparin-anticoagulation, the short and long-term outcomes of these patients would be improved. PATIENTS: Sixty-six consecutive patients with combined liver and kidney failure SETTING: Intensive Care Unit of tertiary hospital DESIGN: Retrospective interrogation of prospectively collected databases INTERVENTION: Treatment of all patients with continuous veno-venous hemofiltration (CVVH) by protocol with 2L/h of ultrafiltration rate and minimal use of circuit heparinization. Retrieval of specific information on demographic, clinical, therapeutic and outcome details. MEASUREMENTS AND MAIN RESULTS: From July 1995 to April 2004, 66 patients with combined liver and renal failure received continuous veno-venous hemofiltration (CVVH). Of these, 26 received liver transplantation and 40 did not. There were no significant differences in age, APACHE II score, bilirubin, ALT, INR or albumin on admission. The average duration of CVVH was 9.5 days for OLTx patients and 5 days for non-transplanted patients (p=0.013). Heparin anticoagulation was used in only 12% of OLTx patients and 20% of non-transplanted patients. ICU mortality was 15% in OLTx patients and 63% in non-transplanted patients (p<0.0005); hospital mortality was 23% compared to 70% (p<0. 001). Mean survival time at follow up was 1,120 days compared to 358 days (p<0.0001). CONCLUSIONS: ARF associated with OLTx has a much better outcome than ARF without OLTx. Furthermore, management based on a conservative anticoagulation policy and CVVH as the exclusive form of renal support was associated with the best ICU, hospital and long term survival reported so far.

Cause of Death↗
PubMed2003

Cryoprecipitate for the correction of coagulopathy associated with liver disease.

In patients with liver disease at risk of pulmonary oedema, cryoprecipitate (small volume) might be a viable alternative to fresh frozen plasma (FFP, large volume) in the correction of coagulopathy. However, the efficacy of cryoprecipitate in these patients has not been tested. We evaluated the role of cryoprecipitate in the correction of the coagulopathy of liver disease. To establish initial evidence of efficacy, six consecutive patients with hepatic failure and coagulopathy received five units of cryoprecipitate. Then, using a crossover design, 11 consecutive patients were randomized to receive either four units of FFP or five units of cryoprecipitate. Pre and post infusion International Normalized Ratio (INR), activated Partial Thromboplastin Time (aPTT), fibrinogen D-dimers, Factors V and IX, and reptilase time were measured. In the first six patients, cryoprecipitate improved the INR, aPTT and fibrinogen concentration (P = 0.03). In the crossover study, FFP administration produced a greater improvement in INR (P = 0.007) and aPTT (P = 0.005) than cryoprecipitate. However, there were no differences in any of the other measured variables. One patient developed acute pulmonary oedema while receiving FFP. Cryoprecipitate improves the coagulopathy of liver disease. Four units of FFP are more efficacious than five units of cryoprecipitate. Cryoprecipitate may have a role in correction of the coagulopathy associated with liver disease where concerns about pulmonary oedema exist.

Adult↗
PubMed2002

Paediatric liver transplantation [corrected] in Melbourne: the first 50 patients.

To report the outcomes of the first 50 paediatric patients who have undergone liver transplantation (LT) at the Victorian Liver Transplant Unit, a retrospective review of case records was carried out. From December 1988 to December 2000, 108 patients 18 years or younger were referred for LT; 50 of these underwent a total of 53 transplants. The most common indications were biliary atresia (32%), metabolic disease (26%), and acute hepatic necrosis (26%). The majority of deaths (6/7) occurred in the 1st week after LT. The actuarial survival at 1 year was 88% (95% CI 75% to 94%) and at 10 years 85% (95% CI 71% to 93%). Survival rates were highest for children aged 3 to 14 years (95%) and lowest in those weighing less than 8 kg at the time of LT (66%). All 43 survivors are attending age-appropriate activities including kindergarten, school, and employment. The survival of patients undergoing LT in this unit compares favourably with those recorded by the Australia and New Zealand Transplant Registry and is commensurate with that reported by larger paediatric transplant programs overseas.

Adolescent↗
PubMed2001

Hepatocellular carcinoma and chemoembolization.

BACKGROUND: Chemoembolization is often used in the treatment of hepatocellular carcinoma; however, there are limited data on its efficacy in an Australian setting. AIMS: To review retrospectively the experience of 21 patients with hepatocellular carcinoma who collectively had 36 chemoembolizations performed between October 1995 and February 1999 in a teaching hospital and liver transplant centre in Victoria. METHODS: Selective catheterization of the right or left hepatic arteries was performed. A mixture of cisplatin 50 mg, epirubicin 50 mg, mitomycin C 10 mg, Lipiodol and gelfoam was injected. Computed tomography (CT) scans were performed at baseline and at 1-3 months after chemoembolization. Outcome measures included response rates, toxicity, progression-free and overall survival. RESULTS: CT response rates: partial response 19% (n = 7), median duration 11 months (range 2+ to 37+); minor response 17% (n = 6), median duration 7 months (1+ to 12+); stable disease 42% (n = 15), median duration 3 months (1+ to 15 months); and progressive disease 22% (n = 8). Major toxicities included one case each of acute renal failure, contrast encephalopathy, gastric ulceration and hepatorenal failure. Median progression-free survival was 3 months (range 0-37+). Median overall survival was 15 months (range 6-50+). CONCLUSION: Chemoembolization has a role in the palliative treatment of hepatocellular carcinoma. Our response rates and toxicity data are consistent with those in the published literature. However, new treatments are needed and prevention of disease by reduction in the prevalence of chronic hepatitis B and C will be required to significantly reduce mortality from this tumour.

Adult↗
PubMed2001

Duck hepatitis B virus replication in primary bile duct epithelial cells.

Primary cultures of intrahepatic bile duct epithelial (IBDE) cells isolated from duckling livers were successfully grown for studies of duck hepatitis B virus (DHBV). The primary IBDE cells were characterized by immunohistochemistry using CAM 5.2, a cytokeratin marker which was shown to react specifically to IBDE cells in duck liver tissue sections and in primary cultures of total duck liver cells. Immunofluorescence assay using anti-duck albumin, a marker for hepatocytes, revealed that these IBDE cultures did not appear to contain hepatocytes. A striking feature of these cultures was the duct-like structures present within each cell colony of multilayered IBDE cells. Normal duck serum in the growth medium was found to be essential for the development of these cells into duct-like structures. When the primary cultures of duck IBDE cells were acutely infected with DHBV, dual-labeled confocal microscopy using a combination of anti-DHBV core proteins and CAM 5.2 or a combination of anti-pre-S1 proteins and CAM 5.2 revealed that the IBDE cell colonies contained DHBV proteins. Immunoblot analysis of these cells showed that the DHBV pre-S1 and core proteins were similar to their counterparts in infected primary duck hepatocyte cultures. Southern blot analysis of infected IBDE preparations using a digoxigenin-labeled positive-sense DHBV riboprobe revealed the presence of hepadnavirus covalently closed circular (CCC) DNA, minus-sense single-stranded (SS) DNA, double-stranded linear DNA, and relaxed circular DNA. The presence of minus-sense SS DNA in the acutely infected IBDE cultures is indicative of DHBV reverse transcriptase activity, while the establishment of a pool of viral CCC DNA reveals the ability of these cells to maintain persistent infection. Taken collectively, the results from this study demonstrated that primary duck IBDE cells supported hepadnavirus replication as shown by the de novo synthesis of DHBV proteins and DNA replicative intermediates.

Animals↗
PubMed2000

Effect of nucleoside analogue therapy on duck hepatitis B viral replication in hepatocytes and bile duct epithelial cells in vivo.

BACKGROUND: Recent studies have implicated bile duct epithelial cells (BDEC) as a reservoir of hepatitis B virus (HBV) infection that may be particularly important in the development of post-liver transplant recurrence of hepatitis B. The aim of this study was to compare the effects of antiviral therapy on duck HBV (DHBV) expression in hepatocytes and BDEC and to determine if this was affected by biliary hyperplasia. METHODS: Ducklings congenitally infected with DHBV received penciclovir (10 mg/kg per day) treatment from 9 days of age. In order to mimic the biliary hyperplasia that often accompanies severe post-liver transplant HBV recurrence, half the animals underwent bile duct ligation. Duck HBV-DNA in serum was measured at day 1, and serum and liver DHBV-DNA were determined when the animals were killed on day 17. Intrahepatic expression of viral preS1 antigen and DHBV-DNA was measured by immunohistochemistry and in situ hybridization, respectively. RESULTS: Viraemia became undetectable in the penciclovir-treated animals at day 17, following 8 days of therapy. Examination of liver tissue revealed that all hepatocytes and the majority of BDEC contained DHBV preS1 antigen and DHBV-DNA. Penciclovir greatly reduced the intrahepatic viral burden, but there was no antiviral effect on viral markers within BDEC. Despite the increased number of BDEC after bile duct ligation, the same proportion of BDEC was seen to be infected, and this was unaffected by antiviral therapy. CONCLUSIONS: In the duck model with and without biliary hyperplasia, penciclovir controls DHBV replication and reduces viral burden in hepatocytes, but not in BDEC. The BDEC appear to be an important reservoir of virus that is relatively unaffected by antiviral treatment, and may play an important role in disease persistence and relapse following cessation of therapy.

Acyclovir↗
PubMed1998

Relationships among liver and kidney volumes, lean body mass and drug clearance.

AIMS: To determine whether lean body mass (LBM), a possible surrogate of liver and kidney volumes, correlates with hepatic and renal drug clearances. METHODS: Twenty-one disease-free patients with a history of cancer and with normal hepatic and renal function were studied. Salivary pharmacokinetics of oral antipyrine (1200 mg) and 24 h creatinine clearance were determined following the determination of LBM by dual energy X-ray absorptiometry and the determination of liver and kidney volumes by helical CT scanning. RESULTS: Liver volume correlated with LBM (r2=0.21, P=0.04), body surface area (BSA) (r2=0.54, P<0.001), and total body weight (TBW) (r2=0.61, P<0.001). Kidney volume correlated with LBM (r2=0.49, P<0.001), BSA (r2=0.43, P=0.002) and TBW (r2=0.24, P=0.03). Stepwise multiple regression analysis, incorporating the independent variables of age, height, weight, sex, BSA, LBM, alcohol consumption, smoking status and liver volume and the dependent variable antipyrine clearance, indicated that LBM was the only independent correlate of antipyrine clearance. A stepwise multiple regression analysis with kidney volume in the independent variables, and creatinine clearance as dependent variable, showed that kidney volume and age were the only independent correlates of creatinine clearance. A nomogram using serum creatinine and LBM was comparable with the Cockcroft and Gault nomogram in calculating creatinine clearance. CONCLUSIONS: Of the anthropometric variables tested, LBM was the only determinant of antipyrine clearance, but this was not due to a relationship between LBM and liver volume. By contrast, the relationship between creatinine clearance and LBM appeared to be due to a relationship between LBM and kidney volume.

Adult↗
PubMed1997

Hepatitis G virus and fulminant hepatic failure: evidence for transfusion-related infection.

BACKGROUND/AIMS: In the majority of cases of fulminant "viral" hepatitis in Australia, no known aetiological agent can be isolated. We have examined the possible role of the recently discovered hepatitis G virus (HGV) in such cases. METHODS: An HGV specific reverse transcription polymerase chain reaction (RT-PCR) was performed on pre- and post-liver transplant serum from 14 patients who were referred for transplantation at our unit between 1989 and 1995 for unexplained fulminant hepatic failure. Eleven patients successfully underwent transplantation and three died while waiting for a suitable donor organ. Hepatitis viruses A-E were excluded by standard serological and PCR based testing. HGV RT-PCR was also performed on 21 other, randomly selected, liver transplant recipients ("controls"). RESULTS: The 14 fulminant cases were HGV RT-PCR negative prior to transplantation while five of 21 controls were positive. Post-transplant, eight of the 11 fulminant patients were found to be HGV RT-PCR positive and the same five controls remained HGV RT-PCR positive. In three of the eight fulminant patients the HGV infection resolved. CONCLUSIONS: Our data indicate that HGV infection is unlikely to be responsible for fulminant hepatitis and that it is probably acquired from blood and/or blood products during the transplantation process. Furthermore, long-term carriage of HGV post-transplant is not associated with clinically apparent liver disease.

Amino Acid Sequence↗
PubMed1997

Hepatitis B virus polymerase mutations during antiviral therapy in a patient following liver transplantation.

BACKGROUND/AIMS: The purpose of this study was to investigate possible resistance mutations which arose in the polymerase gene of hepatitis B virus (HBV) in a patient with severe recurrent HBV infection following liver transplantation. The patient's management included antiviral chemotherapy for almost 4 years comprising ganciclovir, foscarnet and famciclovir. In the last 2.5 years of famciclovir treatment, an increase in serum HBV DNA levels and a reduced sensitivity of the virion-associated DNA polymerase to penciclovir triphosphate were observed. METHODS: The viral polymerase gene and X gene were sequenced from serum samples collected at representative time intervals covering the entire treatment period. RESULTS: No mutations were detected in the X gene. Three nucleotide mutations, each of which resulted in an altered amino acid sequence, were detected in the polymerase gene after 816 days of total antiviral therapy (370 days of famciclovir). Two of these mutations were detected by direct sequencing and the third was detected after cloning and was present in 10% of the clones. All three mutations occurred in "region B" of RNA-dependent DNA polymerases. The HBV polymerase has similarities to both RNA and DNA polymerases. These mutations in the HBV polymerase gene were located in a similar area to the penciclovir-induced mutations observed in the herpes simplex virus DNA polymerase gene. CONCLUSIONS: Three mutations within the HBV polymerase gene were detected which were associated with a reduced penciclovir sensitivity.

2-Aminopurine↗
PubMed1997

Budd-Chiari syndrome: intractable ascites managed by a trans-hepatic portacaval shunt.

Transjugular intrahepatic portosystemic shunts (TIPS) have recently been used to manage the portal hypertensive complications of the Budd-Chiari syndrome. We report this application of TIPS (to our knowledge the first such application in Australia) in a young man with an excellent result and no major complications. This treatment offers an alternative to portacaval shunt surgery and has the advantage of bypassing a stenosed or compressed inferior vena cava. Additionally, the procedure does not complicate liver transplantation surgery if this is indicated at a later date.

Adult↗
PubMed1996

Retransplantation for precore mutant-related chronic hepatitis B infection: prolonged survival in a patient receiving sequential ganciclovir/famciclovir therapy.

Retransplantation for hepatitis B-related liver allograft failure is rarely successful. Recurrence of infection is almost universal, and the second allograft is invariably lost more rapidly than the first. In a recent multicenter study, only 1 of 20 hepatitis B virus (HBV)-positive patients who underwent liver retransplantation survived beyond 6 months. This report describes the long-term effect of antiviral therapy in a 56-year-old man who was retransplanted for HBV-related allograft loss 14 months after his initial liver transplant. He was treated after the second transplant with intravenous daily ganciclovir. After 10 months of this therapy HBV recurrence was detected. After a change to oral famciclovir therapy, there was a decrease in serum HBV DNA and amino-transferase levels and an improvement in the patient's clinical condition. Famiciclovir therapy has now been continued for 26 months, and the patient remains well 3 years after his second transplant, despite persistent HBV infection and progression to cirrhosis. These observations indicate that the use of long-term antiviral therapy offers promise for improving outcomes in patients who undergo retransplantation after HBV-related liver allograft failure.

2-Aminopurine↗
PubMed1994

Lymphoproliferative disease of donor origin arising in patients after orthotopic liver transplantation.

BACKGROUND: Lymphoproliferative disease is a well recognized complication of organ transplantation and in many cases is associated with Epstein-Barr virus (EBV) infection. It is widely though that posttransplantation lymphoproliferative disease (PTLPD) arises from recipient lymphoid cells. However, solid organ allografts are likely to include donor lymphoid tissue around or within the transplanted organ. Therefore, it is possible that transplanted donor lymphocytes may proliferate to form PTLPD: METHODS: The genetic origin of tumor cells was determined by microsatellite DNA fingerprinting using the polymerase chain reaction (PCR). Their EBV association and clonality were established by PCR amplification of DNA extracted from formalin fixed, paraffin embedded tissue using primers to conserved regions of the EBV genome and the immunoglobulin heavy chain gene, respectively. RESULTS: The authors have demonstrated two cases of lymphoproliferative disease that were derived from donor lymphocytes in orthotopic liver transplant recipients. In both cases, the proliferating cells were EBV DNA positive. Furthermore, the PTLPD was restricted to allograft tissue around the porta hepatis. However, the two cases differed in their clonal properties and response to treatment: one case was oligoclonal and regressed after antiviral therapy and a modest reduction of immunosuppression, whereas the other contained two clonal populations and was controlled only after treatment with antineoplastic chemotherapy. CONCLUSION: This study has demonstrated two cases of PTLPD that were derived from donor lymphoid tissue. Although both cases were associated with EBV and remained localized to allograft tissue, their clonality and response to therapy differed.

Adult↗
PubMed1992

Hepatitis due to nitrofurantoin.

OBJECTIVE: To report three cases of hepatitis related to the use of nitrofurantoin. CLINICAL FEATURES: Two patients who had been taking nitrofurantoin for several years, presented with severe liver failure. In both, the drug had been continued despite evidence of liver injury. A third patient presented with acute hepatitis after six weeks of nitrofurantoin therapy. INTERVENTION AND OUTCOME: One of the patients with liver failure died and the other underwent a successful liver transplantation. The third patient recovered after withdrawal of the drug. CONCLUSION: These cases emphasise the potential for serious hepatic reactions with nitrofurantoin, the danger of continuing the drug once liver damage has occurred and the need for careful monitoring of liver function during long-term therapy.

Adult↗
PubMed1992

Oral fluticasone propionate in active distal ulcerative colitis.

Fluticasone propionate is a new corticosteroid with low systemic bioavailability. This study reports the outcome of a double blind clinical trial comparing oral fluticasone propionate (5 mg four times daily) with placebo for the treatment of active distal ulcerative colitis. Sixty patients were treated for four weeks, with assessments at two and four weeks. One patient was withdrawn when she was found to have amoebiasis. Thus, results are presented for 29 patients who received placebo and 30 who received fluticasone propionate. The two groups were well matched for age, sex, length of history, and extent of disease. After four weeks of therapy the clinical, sigmoidoscopic, and histological responses were similar in the two groups. It is concluded that fluticasone propionate (5 mg four times daily) is not effective treatment for active distal ulcerative colitis.

Administration, Oral↗