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ALD Patients (ald + patient)

Distribution by Scientific Domains

Medical Sciences	75%

Selected Abstracts

Adrenoleukodystrophy: subcellular localization and degradation of adrenoleukodystrophy protein (ALDP/ABCD1) with naturally occurring missense mutations

JOURNAL OF NEUROCHEMISTRY, Issue 6 2007
Norimasa Takahashi
Abstract Mutation in the X-chromosomal adrenoleukodystrophy gene (ALD; ABCD1) leads to X-linked adrenoleukodystrophy (X-ALD), a severe neurodegenerative disorder. The encoded adrenoleukodystrophy protein (ALDP/ABCD1) is a half-size peroxisomal ATP-binding cassette protein of 745 amino acids in humans. In this study, we chose nine arbitrary mutant human ALDP forms (R104C, G116R, Y174C, S342P, Q544R, S606P, S606L, R617H, and H667D) with naturally occurring missense mutations and examined the intracellular behavior. When expressed in X-ALD fibroblasts lacking ALDP, the expression level of mutant His-ALDPs (S606L, R617H, and H667D) was lower than that of wild type and other mutant ALDPs. Furthermore, mutant ALDP-green fluorescence proteins (S606L and H667D) stably expressed in CHO cells were not detected due to rapid degradation. Interestingly, the wild type ALDP co-expressed in these cells also disappeared. In the case of X-ALD fibroblasts from an ALD patient (R617H), the mutant ALDP was not detected in the cells, but appeared upon incubation with a proteasome inhibitor. When CHO cells expressing mutant ALDP-green fluorescence protein (H667D) were cultured in the presence of a proteasome inhibitor, both the mutant and wild type ALDP reappeared. In addition, mutant His-ALDP (Y174C), which has a mutation between transmembrane domain 2 and 3, did not exhibit peroxisomal localization by immunofluorescense study. These results suggest that mutant ALDPs, which have a mutation in the COOH-terminal half of ALDP, including S606L, R617H, and H667D, were degraded by proteasomes after dimerization. Further, the region between transmembrane domain 2 and 3 is important for the targeting of ALDP to the peroxisome. [source]

Drinking patterns, dependency and life-time drinking history in alcohol-related liver disease

ADDICTION, Issue 4 2009
Jennifer Hatton
ABSTRACT Aims To examine the hypothesis that increases in UK liver deaths are a result of episodic or binge drinking as opposed to regular harmful drinking. Design A prospective survey of consecutive in-patients and out-patients. Setting The liver unit of a teaching hospital in the South of England. Participants A total of 234 consecutive in-patients and out-patients between October 2007 and March 2008. Measurements Face-to-face interviews, Alcohol Use Disorders Identification Test, 7-day drinking diary, Severity of Alcohol Dependence Questionnaire, Lifetime Drinking History and liver assessment. Findings Of the 234 subjects, 106 had alcohol as a major contributing factor (alcoholic liver disease: ALD), 80 of whom had evidence of cirrhosis or progressive fibrosis. Of these subjects, 57 (71%) drank on a daily basis; only 10 subjects (13%) drank on fewer than 4 days of the week,of these, five had stopped drinking recently and four had cut down. In ALD patients two life-time drinking patterns accounted for 82% of subjects, increasing from youth (51%), and a variable drinking pattern (31%). ALD patients had significantly more drinking days and units/drinking day than non-ALD patients from the age of 20 years onwards. Conclusions Increases in UK liver deaths are a result of daily or near-daily heavy drinking, not episodic or binge drinking, and this regular drinking pattern is often discernable at an early age. [source]

Midterm cost-effectiveness of the liver transplantation program of England and Wales for three disease groups

LIVER TRANSPLANTATION, Issue 12 2003
Louise Longworth
Liver transplantation has never been the subject of a randomized controlled trial, and there remains uncertainty about the magnitude of benefit and cost-effectiveness for specific patient groups. This article reports the results of an economic evaluation of adult liver transplantation in England and Wales. Patients placed on the waiting list for a liver transplant were observed over 27 months. The costs and health benefits of a comparison group, representing experience in the absence of liver transplantation, were estimated using a combination of observed data from patients waiting for a transplant and published prognostic models. The analysis focuses on three disease groups, for each of which prognostic models were available: primary biliary cirrhosis (PBC), alcoholic liver disease (ALD), and primary sclerosing cholangitis (PSC). A higher proportion of patients with ALD were assessed for a transplant but not placed on the waiting list. The estimated gain in quality-adjusted life-years from transplantation was positive for each of the disease groups. The mean incremental cost per quality-adjusted life-year (95% bootstrap confidence intervals) from time of listing to 27 months for patients with PBC, ALD, and PSC are £29,000 (£1,000 to £59,000), £48,000 (£12,000 to £83,000) and £21,000 (,£23,000 to £60,000), respectively. In conclusion, liver transplantation increases the survival and health-related quality of life of patients with each of three end-stage liver diseases. However, the extent of this increase differs between different disease groups. Cost-effectiveness estimates were poorer for patients with ALD over the 27-month period than for patients with PBC or PSC. This in part reflects the costs of the higher number of ALD patients assessed for each transplant. [source]

Liver Transplantation for Alcoholic Liver Disease in Europe: A Study from the ELTR (European Liver Transplant Registry)

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2010
P. Burra
Alcohol-related liver disease (ALD) is one of the most common indications for liver transplantation (LT). Long-term outcome after LT for ALD versus other etiologies is still under debate. The aim of this study was to compare outcome after LT of patients with ALD, viral (VIR), and cryptogenic cirrhosis. Donor, graft and recipient ELTR variables were analysed in transplants for alcoholic and nonalcoholic cirrhosis (1988,2005) and were correlated with patient survival. Causes of death and/or graft failure were compared between groups. Nine thousand eight hundred eighty ALD, 10 943 VIR, 1478 ALD + VIR and 2410 cryptogenic (CRYP) liver transplants were evaluated. One, 3, 5 and 10 years graft survival rates after LT in ALD patients were 84%, 78%, 73%, 58%, significantly higher than in VIR and CRYP (p = 0.04, p = 0.05). By multivariate analysis, ALD + VIR (RR 1.14) and viral alone (RR 1.06) were significant risk factors for mortality. De novo tumors, cardiovascular and social causes were causes of death/graft failure in higher percentage in ALD groups versus other etiologies. LT for ALD cirrhosis has a favorable outcome, however, hepatitis C virus co-infection seems to eliminate this advantage. Screening for de novo tumors and prevention of cardiovascular complications are essential to provide better long-term results. [source]