Document Detail


Hyperhomocysteinaemia and endothelial dysfunction in young patients with peripheral arterial occlusive disease.
MedLine Citation:
PMID:  7781664     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Hyperhomocysteinaemia, defined as an abnormally high plasma homocysteine concentration after an oral methionine load, is common in young (< or = 50 years) patients with peripheral arterial occlusive disease. It is thought to predispose to atherosclerosis by injuring the vascular endothelium. Treatment with pyridoxine and/or folic acid may lower plasma homocysteine levels. In mildly hyperhomocysteinaemic patients with peripheral arterial occlusive disease, we studied the effect of daily treatment with pyridoxine (250 mg) plus folic acid (5 mg) on homocysteine metabolism (i.e. plasma concentrations in the fasting state and after methionine loading, in 48 patients) and on endothelial function (in 18 patients). Endothelial function was estimated as the plasma concentrations of the endothelium-derived proteins, von Willebrand factor (vWF), thrombomodulin (TM), and tissue-type plasminogen activator (tPA). At baseline, fasting homocysteine levels were above normal in 24 of the 48 patients (50%); post-load levels, by definition, were above normal in 100% of patients. After 12 weeks of treatment, fasting and post-load levels were normal in 98 and 100% of patients, respectively. Endothelial function was assessed in 18 patients who completed 1 year of treatment. At baseline, median vWF (235%) and TM (57.1 ng mL-1) levels were above normal. At follow-up, vWF levels had decreased to 170% (P = 0.01) and TM levels had decreased to 49 ng mL-1 (P = 0.04). tPA levels were normal at baseline and did not change. Endothelial dysfunction is present in young patients with peripheral arterial occlusive disease and hyperhomocysteinaemia. Pyridoxine plus folic acid treatment normalizes homocysteine metabolism in virtually all patients, and appears to ameliorate endothelial dysfunction.
Authors:
M Van den Berg; G H Boers; D G Franken; H J Blom; G J Van Kamp; C Jakobs; J A Rauwerda; C Kluft; C D Stehouwert
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Publication Detail:
Type:  Clinical Trial; Journal Article    
Journal Detail:
Title:  European journal of clinical investigation     Volume:  25     ISSN:  0014-2972     ISO Abbreviation:  Eur. J. Clin. Invest.     Publication Date:  1995 Mar 
Date Detail:
Created Date:  1995-07-20     Completed Date:  1995-07-20     Revised Date:  2004-11-17    
Medline Journal Info:
Nlm Unique ID:  0245331     Medline TA:  Eur J Clin Invest     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  176-81     Citation Subset:  IM    
Affiliation:
Department of Vascular Surgery, Free University Hospital, Amsterdam, The Netherlands.
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MeSH Terms
Descriptor/Qualifier:
Adult
Amino Acid Metabolism, Inborn Errors / blood,  drug therapy,  physiopathology
Arterial Occlusive Diseases / blood,  complications*,  physiopathology
Biological Markers / blood
Blood Pressure / drug effects
Cholesterol / blood
Endothelium, Vascular / physiopathology*
Fasting
Female
Folic Acid / therapeutic use*
Follow-Up Studies
Homocysteine / blood,  metabolism*
Humans
Male
Methionine / diagnostic use*
Middle Aged
Pyridoxine / therapeutic use*
Smoking
Thrombomodulin / analysis
Time Factors
Tissue Plasminogen Activator / blood
von Willebrand Factor / analysis
Chemical
Reg. No./Substance:
0/Biological Markers; 0/Thrombomodulin; 0/von Willebrand Factor; 454-28-4/Homocysteine; 57-88-5/Cholesterol; 59-30-3/Folic Acid; 63-68-3/Methionine; 65-23-6/Pyridoxine; EC 3.4.21.68/Tissue Plasminogen Activator

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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