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Biomedical subjects

James Neuberger

Publications and source records attributed to James Neuberger.

At least 19 recordsLinked to original sources
PubMed2005

Nutritional markers in liver allograft recipients.

BACKGROUND: Malnutrition is common in patients with end-stage liver disease considered for transplantation, but it is unclear whether this affects the outcome after transplantation. AIM.: To determine whether the severity of malnutrition in liver transplant candidates affects outcome after transplantation. METHODS: We did a prospective study of 61 patients with chronic liver disease accepted for transplantation. FINDINGS: The Child-Pugh and Model for End-Stage Liver Disease (MELD) score correlated significantly but weakly with the mid-arm circumference (MAC) (rho=-0.34 and -0.31, P=0.015 and 0.025, respectively) but not with hand-grip strength, triceps skin-fold thickness (TSFT), or mid-arm muscle circumference. The Child-Pugh score but not the MELD was significantly associated with intensive therapy unit stay but not eventual outcome; there was a weak but statistically significant correlation between death and MAC (rho=+0.29, P=0.04) and TSFT (rho=+0.25, P=0.02). CONCLUSIONS: These findings suggest that nutritional parameters and markers of disease severity do not correlate well with outcomes after transplantation.

Adult↗
PubMed2005

Self-organizing maps can determine outcome and match recipients and donors at orthotopic liver transplantation.

BACKGROUND: There is a relative lack of donor organs for liver transplantation. Ideally, to maximize the utility of those livers that are offered, donor and recipient characteristics should be matched to ensure the best possible posttransplant survival of the recipient. METHODS: With prospectively collected data on 827 patients receiving a primary liver graft for chronic liver disease, we used a self-organizing map (SOM) (one form of a neural network) to predict outcome after transplantation using both donor and recipient factors. The SOM was then validated using a data set of 2622 patients undergoing transplantation in the United Kingdom at other centers. RESULTS: SOM analysis using 72 inputs and two survival intervals (3 and 12 months) yielded three neurons with either higher or lower probabilities of survival. The model was validated using the independent data set. With 20 patients on the waiting list and 10 sequential donor livers, it was possible to demonstrate that the model could be used to identify which potential recipients were likely to benefit most from each liver offered. CONCLUSIONS: With this approach to matching donor livers and recipients, it is possible to inform transplant clinicians about the optimum use of donor livers and thereby effectively make the best use of a scarce resource.

Comorbidity↗
PubMed2005

Chronic allograft dysfunction: diagnosis and management. Is it always progressive?

1. There are many causes of graft dysfunction post-liver transplant, but recurrent disease remains the most common cause. 2. Viral hepatitis, nonalcoholic and alcoholic steatohepatitis, and autoimmune diseases are the most common causes of recurrent disease. 3. Graft hepatitis occurs frequently and in many cases will not progress. 4. Cirrhosis in the absence of any identifiable cause develops in a minority. 5. Treatment is of the underlying cause but some, such as recurrent and de novo autoimmune hepatitis and recurrent primary sclerosing cholangitis may not respond well, and regraft may be required.

Biopsy, Needle↗
PubMed2005

Weight gain and obesity after liver transplantation.

Excessive weight gain is common after liver transplantation and frequently leads to obesity. This has been attributed to immunosuppression. The aim of the present study was to assess the extent of weight gain and the risk factors for weight gain after liver transplantation. Height and estimated dry weight were collected prospectively in consecutive adult liver-transplant patients, transplanted between January 1996 and October 2001. A total of 597 patients (45% female, median age of 50 years; range 16-73) was studied. Eighty-six percentage was transplanted for chronic liver disease. The median weight gain at 1 and 3 years was 5.1 and 9.5 kg above dry weight pretransplant. By 1 and 3 years, 24% and 31% had become obese (defined as a body mass index (BMI) >30 kg/m(2)). There was no significant difference in weight gain between the sexes, those who were obese before transplantation or those who received corticosteroids for >3 months. Weight gain was significantly greater (P < 0.05) in patients aged >50 years and those transplanted for chronic liver disease compared with fulminant liver failure. A pretransplant BMI >30 was a strong indicator that the patient would still have a BMI >30 at 3 years. There was no effect of the type of immunosuppression on weight gain. Obesity is common in the liver transplant population, but it seems to be unrelated to any specific immunosuppressive drug. The greatest weight gain occurs after the first 6 months and intervention with dietary advice at this point could be implemented to minimize the long-term morbidity and mortality risks associated with obesity.

Adolescent↗
PubMed2004

Cloning the human betaretrovirus proviral genome from patients with primary biliary cirrhosis.

Patients with primary biliary cirrhosis (PBC) have both serologic and tissue evidence of infection. A recently identified human betaretrovirus was originally cloned from the biliary epithelium cDNA library of a patient with PBC. By conducting a BLASTN search, the initial partial pol gene fragment was found to have 95% to 97% nucleotide homology with mouse mammary tumor virus (MMTV) and with retrovirus sequences derived from human breast cancer samples. Using an anti-p27(CA) MMTV antibody, viral proteins were detected in the perihepatic lymph nodes but not in liver tissue samples from patients with PBC, suggesting a higher viral burden in lymphoid tissue. Therefore, in the current study, we used lymph node DNA to clone the proviral genome of the human betaretrovirus from two patients with PBC using a polymerase chain reaction (PCR) walking methodology with conserved primers complementary to MMTV. The human betaretrovirus genome contains five potential open reading frames (ORF) for Gag, protease (Pro), polymerase (Pol), envelope (Env), and superantigen (Sag) proteins that are collinear with their counterparts in MMTV. Alignment studies performed with characterized MMTV and human breast cancer betaretrovirus amino acid sequences revealed a 93% to 99% identity with the p27 capsid proteins, a 93% to 97% identity with the betaretrovirus envelope proteins, and a 76% to 85% identity with the more variable superantigen proteins. Phylogenetic analysis of known betaretrovirus superantigen proteins showed that the human and murine sequences did not cluster as two distinct species. In conclusion, human betaretrovirus nucleic acid sequences have been cloned from patients with PBC. They share marked homology with MMTV and human breast cancer-derived retrovirus sequences.

Amino Acid Sequence↗
PubMed2004

Immunosuppression affects the rate of recurrent primary biliary cirrhosis after liver transplantation.

Identifying the risk factors associated with recurrence of primary biliary cirrhosis after liver transplantation may affect immunosuppression and increase understanding of the pathogenesis. Four hundred eighty-five patients with PBC were followed for a median of 79 months after transplantation; histological evidence of recurrence was found in 23%. On multivariate analysis, the only risk factor identified with recurrence was the type of calcineurin inhibitor used. The odds ratio for recurrence on tacrolimus was 2.73 (95% confidence interval: 1.84-4.10) compared with cyclosporine. For those receiving cyclosporine, the median time to recurrence was 123 months and for those on tacrolimus 62 months (P <.001). Reasons for this difference between the 2 calcineurin inhibitors are not clear.

Adult↗
PubMed2004

Options for treatment of primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a chronic progressive cholestatic disease where there is progressive, granulomatous destruction of the middle-sized bile ducts. The disease affects mainly middle-aged women. The association with other autoimmune diseases and the widespread disturbance of the humoral and cellular immune systems has led to the inclusion of PBC as an autoimmune disease. However, there are several lines of evidence that suggest that both host and environmental factors are implicated in triggering the disease. Without a clear aetiology, it is difficult to find a logical approach to treatment. Well constructed clinical trials are difficult to run because of the variable and long natural history of the disease; and suitable endpoints are difficult to define and validated surrogate endpoints have not been defined. The only drug licensed for use is the bile acid, ursodeoxycholic acid. This drug is associated with significant biochemical improvement and improvement in the immunological disturbances (including a reduction in the titre of the diagnostic autoantibody, antimitochondrial antibody), but the effect on survival and histological progression is still controversial. There is little effect on symptoms. Nonetheless, its safety and lack of toxicity have meant that it has become the drug of choice and most studies now assess the effect of additional treatments. Many other agents have been studied. There is some evidence, from prospective, controlled studies, for a beneficial effect of azathioprine and ciclosporin (cyclosporine); evidence for a beneficial effect of corticosteroids and of mycophenolate is limited and there is little firm evidence for a beneficial effect of methotrexate, penicillamine, thalidomide or colchicine. Other treatments being evaluated include fibric acid derivatives (fibrates), NSAIDs and leukotriene antagonists. Liver transplantation remains the only option for end-stage disease but recurrence of disease may be found in the graft. Experimental therapies include antiretroviral therapy. Symptomatic treatment is required for pruritus and the mainstays are the bile acid binding agents such as colestyramine. For those who are intolerant of the drug or where it is ineffective, rifampicin and naltrexone may be effective. There is no effective treatment for the associated lethargy.

Aged↗
PubMed2003

Survival gain after liver transplantation for patients with alcoholic liver disease: a comparison across models and centers.

BACKGROUND: Prognostic models, which estimate survival probabilities, enable the survival benefit from a procedure to be assessed and allow the comparison of outcomes between centers. We therefore compared three models that estimate survival in the absence of transplantation for patients with alcoholic liver disease (ALD) to assess survival benefit after transplantation and to compare the outcomes in the six liver-transplant centers in England. METHODS: The Béclére and Birmingham models and the Model for End-Stage Liver Disease (MELD) were used to estimate survival in the absence of transplantation in a cohort of 82 patients with end-stage ALD. Posttransplant survival in the same cohort of patients was calculated using conventional survival techniques. Each individual's short-term survival gain after liver transplantation was also calculated and compared across UK liver transplant centers. RESULTS: The expected gain in survival differed substantially depending on the model used. Over the 4-year study period, the survival gain for all ALD patients was 1.70 years (95% confidence interval [CI] 1.37-2.03) using the Béclére model, 0.95 years (CI 0.60-1.30) using MELD, and 0.08 years (CI -0.31-0.47) using the Birmingham model. Two centers consistently had greater estimated survival gains up to 4 years postliver transplant regardless of the model used to estimate nontransplant survival. CONCLUSIONS: These findings suggest that although liver transplantation is associated with an improvement in survival, the gain over 4 years is modest. The three models are poorly correlated and should be applied with caution. Survival gain does, however, appear to vary between centers.

Bilirubin↗