Abstract:
BACKGROUND:Thiopurines (TP) are widely used in the management of inflammatory bowel diseases. Side effects and inefficacy are a major concern as they lead to withdrawal of the drug. MATERIALS AND METHODS:Tools investigating TP metabolism are useful to avoid inadequate cessation of TP therapy. RESULTS:TP metabolism is complex and many enzymes are involved. Among them, Thiopurine methyl transferase is the only one routinely measured by pheno- or genotyping. A decreased TPMT activity results in a potential overdosing of TP drugs leading to myelotoxicity, whereas an ultra-high activity leads to TP ineffectiveness and overproduction of methylated compounds responsible for hepatotoxicity. TPMT determination prior to TP treatment results in an individual adapted dose. Xanthine oxidase/dehydrogenase (XOD), inosine triphosphate pyrophosphatase (ITPA) and glutathion-S-transferase (GST) are other promising enzyme targets that might help to explain TP efficacy or toxicity. ITPA and GST polymorphisms might potentially be related to some TP side effects, while a XOD inhibition by allopurinol could avoid TP-related hepatotoxicity. CONCLUSIONS:Utilization of thiopurine metabolites, 6-thioguanine nucleotides and 6-methylmercaptopurine, is discussed, specifically, in case of thiopurine failure and recommendations are given about their interpretation and potential dose optimization. These enzymes and metabolites tests are complementary to the regular monitoring of blood cells count and liver tests which remains mandatory.
journal_name
Eur J Clin Investjournal_title
European journal of clinical investigationauthors
Dewit O,Starkel P,Roblin Xdoi
10.1111/j.1365-2362.2010.02346.xsubject
Has Abstractpub_date
2010-11-01 00:00:00pages
1037-47issue
11eissn
0014-2972issn
1365-2362pii
ECI2346journal_volume
40pub_type
杂志文章,评审abstract:BACKGROUND:Our aim in the present study was to determine whether endothelial NO synthase gene (ecNOS) polymorphisms are associated with myocardial infarction (MI). METHODS:Forty chromosomes from patients with MI were screened for polymorphisms of the ecNOS gene using polymerase chain reaction-single-strand conformatio...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1046/j.1365-2362.1999.00451.x
更新日期:1999-04-01 00:00:00
abstract::In twenty-five outpatients with essential hypertension, the relevance of renal kallikrein excretion for inter-individual differences in the blood pressure response to changes in dietary sodium intake was investigated. The patients were studied during 2 weeks of high (300 mmol) and 2 weeks of low (50-100 mmol) sodium i...
journal_title:European journal of clinical investigation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1111/j.1365-2362.1985.tb00160.x
更新日期:1985-06-01 00:00:00
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journal_title:European journal of clinical investigation
pub_type: 杂志文章
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更新日期:1992-02-01 00:00:00
abstract::Portal-systemic spill-over of unconjugated ursodeoxycholic acid (UDCA) was assessed in ten healthy subjects, six patients with mild chronic liver disease and eight patients with cirrhosis. Following oral administration of UDCA (1.5 mg/kg body weight), serum concentrations of unconjugated UDCA were measured during 2 h ...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.1983.tb00126.x
更新日期:1983-12-01 00:00:00
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journal_title:European journal of clinical investigation
pub_type: 杂志文章
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journal_title:European journal of clinical investigation
pub_type: 杂志文章,评审
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更新日期:2017-11-01 00:00:00
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journal_title:European journal of clinical investigation
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journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.1985.tb00147.x
更新日期:1985-04-01 00:00:00
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journal_title:European journal of clinical investigation
pub_type: 杂志文章
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更新日期:1978-08-01 00:00:00
abstract:BACKGROUND:It remains unsettled whether alcoholic cirrhosis is a risk factor for myocardial infarction (MI). METHODS:We used data from nationwide healthcare registries to study all Danes diagnosed with alcoholic cirrhosis in 1996-2014, and five controls were matched to each of them on gender and age. We excluded every...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
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更新日期:2020-04-01 00:00:00
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pub_type: 杂志文章
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journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1046/j.1365-2362.2001.00892.x
更新日期:2001-10-01 00:00:00
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journal_title:European journal of clinical investigation
pub_type: 杂志文章,随机对照试验
doi:10.1111/j.1365-2362.2005.01573.x
更新日期:2005-12-01 00:00:00
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journal_title:European journal of clinical investigation
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更新日期:2002-06-01 00:00:00
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journal_title:European journal of clinical investigation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1046/j.1365-2362.1999.00579.x
更新日期:1999-12-01 00:00:00
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journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.1984.tb02100.x
更新日期:1984-04-01 00:00:00
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journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.2011.02476.x
更新日期:2011-08-01 00:00:00
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journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.1980.tb00011.x
更新日期:1980-02-01 00:00:00
abstract::Pulmonary plasma kinetics of endogenous noradrenaline (NA) and tritium labelled L-noradrenaline (3H-NA) was studied in fifteen subjects during pulmonary arterial catheterization. Plasma NA concentration in femoral artery ranged from 0.5 to 8.2 nmol l-1, mean 2.3 nmol l-1, which was not significantly different from tha...
journal_title:European journal of clinical investigation
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journal_title:European journal of clinical investigation
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journal_title:European journal of clinical investigation
pub_type: 杂志文章,随机对照试验
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更新日期:2011-06-01 00:00:00
abstract::Levels of free anti-(xanthine oxidoreductase) (XOR) antibodies in the serum of normal healthy human subjects were determined, using both human and bovine enzyme as antigen, in an enzyme-linked immunosorbent assay (ELISA). Levels of IgM class anti-(human XOR) antibodies were found to be particularly high (mean values r...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
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abstract:INTRODUCTION:Asymptomatic carotid artery stenosis (ACAS) may cause future stroke and therefore patients with ACAS require best medical treatment. Patients at high risk for stroke may opt for additional revascularization (either surgery or stenting) but the future stroke risk should outweigh the risk for peri/post-opera...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
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更新日期:2020-12-01 00:00:00
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journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1046/j.1365-2362.2001.00795.x
更新日期:2001-05-01 00:00:00
abstract:BACKGROUND:Diverticular disease (DD) and irritable bowel syndrome (IBS) share a similar symptom pattern. However, comparative studies are flawed by different age at onset of symptoms. We aimed to verify whether clinical features distinguish DD from IBS. MATERIALS AND METHODS:Patients with DD or IBS, matched for age an...
journal_title:European journal of clinical investigation
pub_type: 杂志文章,多中心研究
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更新日期:2013-11-01 00:00:00
abstract:BACKGROUND:The DALI low-density lipoprotein (LDL) apheresis system is the first whole-blood apheresis system in regular clinical use. DALI stands for direct adsorption of lipoproteins, which describes the basic principle of operation of this newly developed LDL apheresis procedure. METHODS:The selective removal of LDL...
journal_title:European journal of clinical investigation
pub_type: 临床试验,杂志文章,多中心研究
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更新日期:1998-12-01 00:00:00
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journal_title:European journal of clinical investigation
pub_type: 杂志文章,随机对照试验
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更新日期:2010-02-01 00:00:00
abstract:BACKGROUND:HFE knockout mice (C57BL/6 x 129/Ola strain) mimic the functional aberrations of human hereditary haemochromatosis (HH) in short-term experiments. The present study investigates functional and morphological long-term changes. METHODS:HFE(o/o), HFE(+/o) and HFE(+/+) mice were maintained on iron-rich and cont...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1046/j.1365-2362.2002.01026.x
更新日期:2002-08-01 00:00:00
abstract::The effect of renal function on the cyclic AMP (cAMP) response to exogenous parathyroid hormone (PTH) was examined in patients with chronic renal failure (n = 22) and primary hyperparathyroidism (n = 19). In the patients with chronic renal failure there was marked resistance to the effect of exogenous PTH. In primary ...
journal_title:European journal of clinical investigation
pub_type: 杂志文章
doi:10.1111/j.1365-2362.1985.tb00141.x
更新日期:1985-02-01 00:00:00