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Biomedical subjects

A Burroughs

Publications and source records attributed to A Burroughs.

At least 19 recordsLinked to original sources

Primary herpes simplex virus type-2 infection as a cause of liver failure after liver transplantation.

We report a case of fatal primary herpes simplex virus type-2 (HSV-2) infection following liver transplantation, which manifested with fever and liver failure in the absence of muco-cutaneous disease. The infection was characterized by high levels of HSV DNA in blood and the patient's inability to mount HSV-specific T-cell responses while showing preserved T-cell responses against cytomegalovirus. The donor was HSV-1 immunoglobulin G (IgG) seronegative and HSV-2 IgG seropositive, whereas the recipient was HSV-1 and HSV-2 IgG seronegative, suggesting that the graft may have been the source of the infection. In HSV-seronegative recipients of grafts from HSV-seropositive donors, HSV infection should be included in the differential diagnosis of a febrile illness, regardless of the absence of muco-cutaneous disease. In this setting, real-time polymerase chain reaction applied to blood samples provides a sensitive, rapid, and quantitative diagnostic tool.

Adult↗

Public awareness of risk factors and screening for colorectal cancer in Europe.

Colorectal cancer (CRC) is the commonest site for malignancy in Europe. The Commissioner for Health wishes to promote screening for colorectal, breast and cervical cancer in Europe. The aim of this study was to assess public knowledge of CRC in Europe and likely take up of free screening. To this end 20710 members of the public from 21 European countries were interviewed by means of a regular survey amongst consumers (Omnibus survey) using 13 stem questions. Forty-eight per cent thought the population were at equal risk of CRC, only 57% were aware of age and 54% of family history as risk factors. Although 70% were aware of dietary factors, only 30% knew that lack of exercise might be a risk factor. Only 51% had knowledge of CRC screening but 75% were 'very', or 'quite interested, in taking up faecal occult blood (FOB) screening if offered free. Barriers to screening were lack of awareness of risk (31%), youth (22%) and an un-anaesthetic test (19%). There was a big cultural difference in willingness of the public to discuss bowel symptoms: there was a major barrier in Finland (91%), Britain (84%), Luxembourg (82%), Poland (81%) and Portugal (80%); less of a barrier in Spain (49%), Italy (44%) and Iceland (39%). In conclusion, the challenge of achieving high compliance for CRC screening must be a major objective amongst EU member states and non-aligned countries of Europe in the next decade, because it is known that the non-compliant group are those at greatest risk of death from CRC. This study has shown that awareness of CRC is low in Europe and that an educational programme will be essential to achieve high compliance for CRC screening as a means of reducing deaths from bowel cancer.

Adult↗

Tacrolimus versus microemulsified ciclosporin in liver transplantation: the TMC randomised controlled trial.

BACKGROUND: Calcineurin inhibitors are the most commonly used immunosuppressive drugs in liver transplantation, but the optimum initial immunosuppression regimen is not known. The aim of our study was to compare tacrolimus with microemulsified ciclosporin, in a regimen with standardised concomitant immunosuppressive therapy. METHODS: In all liver transplant centres in the UK and Republic of Ireland, 606 patients undergoing a first orthotopic liver transplantation were randomly assigned open-label tacrolimus or microemulsified ciclosporin. Primary outcome was the combined frequency (whichever occurred first) of death, retransplantation, or treatment failure for immunological reasons, analysed by intention to treat. FINDINGS: 96% of patients received the treatment allocated to them. The primary outcome was reached in 62 (21%) of 301 patients in the tacrolimus group versus 99 (32%) of 305 allocated microemulsified ciclosporin (relative risk 0.63 [95% CI 0.48-0.84], p=0.001; time-to-event analysis log-rank test p=0.002): deaths (50 [17%] vs 72 [24%]); retransplantations (11 [4%] vs 31 [10%]) treatment failure for immunological reasons (6 [2%] vs 12 [4%]). The relative risk for the composite outcome was in favour of tacrolimus. The main causes of death in both trial groups were sepsis and multiple organ failure (31 [10%] vs 30 [10%]), and the main cause for retransplantation was hepatic artery thrombosis (6 [2%] vs 17 [6%]). Renal dysfunction and the need for antihypertensive therapy were much the same in both groups. Tacrolimus was more diabetogenic. INTERPRETATION: Clinical outcome at 1 year was better with tacrolimus-based immunosuppression than with microemulsified ciclosporin during the first year after liver transplantation. Tacrolimus should be the first choice of calcineurin inhibitor for patients receiving their first liver graft.

Administration, Oral↗

A simulation modelling approach to evaluating alternative policies for the management of the waiting list for liver transplantation.

A shortage of donor liver grafts unfortunately results in approximately 10% of patients dying whilst listed for a liver transplant in Europe and the United States. Thus it is imperative that all available organs are used as efficiently as possible. This paper reports upon the application of a simulation modelling approach to assess the impact of several alternative allocation policies upon the cost effectiveness of this technology at one liver transplant centre in the UK. The impact of changes in allocation criteria on the estimated net life expectancy, average net costs and overall cost effectiveness of the transplantation programme were evaluated. The incremental cost effectiveness ratio (ICER) for the base case allocation policy, based upon the time spent on the waiting list (i.e., longest wait first) was 11,557 pounds sterling at 1999 prices. The ICERs associated with an allocation policy based upon age (lowest age first), and an allocation policy based upon the severity of the pre-transplant condition of the patient (with most severely ill patients given a lower priority) were lower than the base case at 10,424 pounds sterling and 9,077 pounds sterling, respectively. The results of this modelling study suggest that the overall cost effectiveness of the liver transplantation programme could be improved if the current allocation policy were modified to give more weight to the age of the patient and the reduced chances of success of the most severely ill patients.

Cost-Benefit Analysis↗

Variceal bleeding and portal hypertensive gastropathy.

Cirrhosis can be the end stage of any chronic liver disease. At the time of diagnosis of cirrhosis varices are present in about 60% of decompensated and 30% of compensated patients. The risk factors for the first episode of variceal bleeding in cirrhotic patients are the severity of liver dysfunction, large size of varices and the presence of endoscopic red colour signs but only one-third of patients who have variceal haemorrhage have the above risk factors. Recent interest has been directed at identifying haemodynamic factors that may reflect the pathophysiological changes which lead to variceal bleeding, e.g. it has been confirmed that no bleeding occurs if HVPG falls below 12 mmHg and also a hypothesis has been put forward in which bacterial infection is considered a trigger for bleeding. Pharmacological treatment with beta-blockers is safe, effective and is the standard long-term treatment for the prevention of recurrence of variceal bleeding. Combination of beta-blockers with isosorbide-5-mononitrate needs further testing in randomized controlled trials. The use of haemodynamic targets for reduction in HVPG response needs further study, and surrogate markers of pressure response need evaluation. If endoscopic treatment is chosen, variceal ligation is the modality of choice. The combination of simultaneous variceal ligation and sclerotherapy does not offer any benefit. However, the use of additional sclerotherapy for the complete eradication of small varices after variceal ligation needs to be evaluated. The results of current prospective randomized controlled trials comparing variceal ligation with pharmacological treatment are awaited with great interest. Finally, the use of transjugular intrahepatic portosystemic shunt (TIPS) for the secondary prevention of variceal bleeding is not substantiated by current data, as survival is not improved and because of its worse cost-benefit profile compared to other treatments. In contrast, there still is a role for the selective surgical shunts in the modern management of portal hypertension. The ideal patients should be well compensated cirrhotics, who have had troublesome bleeding - either who have failed at least one other modality of therapy (drugs or ligation), have bled from gastric varices despite medical or endoscopic therapy, or live far from suitable medical services. Recently, ligation has been compared to beta-blockers for primary prophylaxis but so far there is no good evidence to recommend banding for primary prophylaxis, if beta-blockers can be given.

Adrenergic beta-Antagonists↗

Lamivudine without HBIg for prevention of graft reinfection by hepatitis B: long-term follow-up.

BACKGROUND: This open, multicenter study was conducted to evaluate the efficacy and safety of lamivudine prophylaxis given to chronic hepatitis B virus-(HBV) infected patients before and after orthotopic liver transplantation (OLT). We now present long-term data that follow our previous short-term report. METHODS: Twenty-three patients were treated with lamivudine (100 mg orally, daily); 13 (57%), were serum HBV DNA positive (Abbott Genostics, Abbott Laboratories, Chicago, IL) at study entry. Patients received lamivudine for at least 4 weeks before OLT, and for up to 50 months (median 25 months) after OLT. RESULTS: Of the 23 treated patients, 17 survived to undergo OLT. Eleven patients (65%) survived up to 4 years (median 36 months) after OLT. One of the survivors stopped lamivudine because of a possible adverse reaction 9 months post-OLT, and prophylaxis with HBV immune globulin was then established. Ten survivors continue lamivudine. Eight long-term survivors have normal liver function without evidence of HBV reinfection. Of the 17 transplanted patients, 6 died. Four patients died (3 days to 5 months post-OLT) without evidence of graft reinfection. Two further patients died at 19 and 23 months post-OLT from graft failure. Both patients had YMDD variant detected at 12 months post-OLT. Two other patients with YMDD-variant HBV remain alive on lamivudine, 9 and 15 months after development of the variant. CONCLUSIONS: Lamivudine, given before and after OLT, prevents significant graft reinfection for the majority of treated patients. The study has also shown that lamivudine is extremely well tolerated by liver failure patients and for a prolonged period after transplantation.

Biopsy↗

Liver transplantation complicated by embedded transjugular intrahepatic portosystemic shunt: a new method for portal anastomosis- a surgical salvage procedure.

A transjugular intrahepatic portosystemic shunt (TIPS) is an increasingly used method of treating variceal bleeding from portal hypertension. Many patients are subsequently listed for transplantation, which may be complicated by malposition of the inferior end of the TIPS stent. This report details such a case and offers a surgical technique to salvage this situation.

Adult↗

Results of choledochojejunostomy in the treatment of biliary complications after liver transplantation in the era of nonsurgical therapies.

Advances in radiological and endoscopic techniques have allowed many biliary complications after orthotopic liver transplantation (OLT) to be managed without surgery. The influence of nonsurgical management on the outcome of patients requiring surgical revision has not been addressed. We reviewed our 10-year experience (October 1988 to January 1998) of Roux-en-Y choledochojejunostomy (CDJ) to treat biliary complications after OLT. Forty-six patients underwent CDJ for biliary complications (32 men, 14 women; age, 22 to 65 years; median, 60 years). Biliary reconstruction at the time of OLT was duct to duct in 41 patients, primary CDJ in 3 patients, and gall bladder conduit in 2 patients. T-tubes were used only in patients with gallbladder conduit. The indication for CDJ was biliary leak (23 patients), stricture (20 patients), biliary stones (2 patients), and biliary sludge (1 patient). Two patients (4.3%) had associated hepatic artery thrombosis. The bile leaks were diagnosed at a median of 29 days post-OLT (range, 2 to 65 days) and strictures at a median of 2 years (range, 33 days to 6.5 years) post-OLT. Before surgery, 25 patients (54%) underwent an attempt at radiological or endoscopic therapeutic intervention that failed. Median follow-up was 5 years (range, 9 months to 10 years). Early complications occurred in 12 patients (26%); the most common was chest infection (4 patients). There were 3 perioperative deaths (6%); 1 death was directly related to surgery. Late complications, mainly anastomotic strictures, occurred in 10 patients (22%), half of which were successfully treated by biliary balloon dilatation. The complication rate post-CDJ was less in those who underwent a failed nonsurgical approach than those proceeding straight to surgery (9 of 25 patients; 36% v 13 of 21 patients; 62%; P =.21, not significant). The procedure-related mortality for surgical revision of biliary complications after OLT is low, but early and late complications are common. A failed attempt at nonsurgical management does not increase the complications of reconstructive surgery. Strictures after CDJ should be considered for biliary balloon dilatation.

Adult↗

Review article: pharmacological treatment of the hepatorenal syndrome in cirrhotic patients.

Renal failure is common in patients who are dying from end-stage cirrhosis, developing in 40-80% of all patients. Where there is no anatomical or pathological cause for the renal failure, it is termed the hepatorenal syndrome. When the hepatorenal syndrome develops, it will only recover when there is some degree of improvement in liver function. Thus for most patients this will occur only after liver transplantation, although the transplantation mortality is increased in this group. Hepatorenal syndrome is a common complication of alcoholic hepatitis, and this group is unusual in that with time and abstinence, significant recovery of liver function may occur. There is therefore a need for supportive therapy to allow time for some recovery of liver function in patients with alcoholic hepatitis and hepatorenal syndrome. Similarly, patients may need support whilst waiting for liver transplantation. This article reviews the pathophysiology and treatment of hepatorenal syndrome.

Disease Progression↗

Drug treatment for bleeding oesophageal varices.

At the time of diagnosis of cirrhosis, varices are present in about 60% of decompensated and 30% of compensated patients. The risk factors for the first episode of variceal bleeding in cirrhotic patients are the severity of liver dysfunction, a large size of the varices and the presence of endoscopic red colour signs, but only a third of patients who suffer variceal haemorrhage demonstrate the above risk factors. The only treatment that does not require sophisticated equipment or the skills of a specialist, and is immediately available, is vasoactive drug therapy. Hence, drug therapy should be considered to be the initial treatment of choice and can be administered while the patient is transferred to hospital, as has been done in one recent study. Moreover, drug therapy is no longer considered to be only a 'stop-gap' therapy until definitive endoscopic therapy is performed. Several recent trials have reported an efficacy similar to that of emergency sclerotherapy in the control of variceal bleeding. Furthermore, recent evidence suggests that those patients with high variceal or portal pressure are likely to continue to bleed or re-bleed early, implying that prolonged therapy lowering the portal pressure over several days may be the optimal treatment. Pharmacological treatment with beta-blockers is safe, effective and the standard long-term treatment for the prevention of recurrence of variceal bleeding. The combination of beta-blockers with isosorbide-5-mononitrate needs further testing in randomized controlled trials. The use of haemodynamic targets for the reduction of the HVPG response needs further study, and surrogate markers of the pressure response need evaluation. Ligation has recently been compared with beta-blockers for primary prophylaxis, but there is as yet no good evidence to recommend banding for primary prophylaxis if beta-blockers can be given.

Acute Disease↗

Management of oesophageal varices.

Beta-blockers are the treatment of choice to prevent the first episode of variceal bleeding and further rebleeding episodes. In acute bleeding all patients should receive pharmacological treatment with vasoconstrictors and endoscopic treatment. Failure of therapy should lead to consideration of transjugular intrahepatic portosystemic shunting.

Adrenergic beta-Antagonists↗

Psychiatric and social outcome following liver transplantation for alcoholic liver disease: a controlled study.

Psychiatric outcome, quality of life, and alcohol consumption were compared between patients transplanted for alcoholic liver disease and those transplanted for other chronic liver diseases. Instruments used included the Clinical Interview Schedule, the 28-item General Health Questionnaire, the Hospital Anxiety and Depression Scale, and the Nottingham Health Profile. There was no difference between the two groups with regard to median scores or "caseness" on these instruments, except for physical mobility on the Nottingham Health Profile, where the alcoholic group was more likely to experience difficulties (p = 0.03). The majority of those transplanted for alcoholic liver disease remained abstinent, although 7 of the 31 in the alcoholic group (23%) were drinking above recommended safe limits. Psychosocial outcome is similar for individuals transplanted for alcoholic liver disease and those transplanted for other chronic liver diseases. Patients should not be excluded from transplantation on grounds of their drinking history.

Adult↗