Showing papers by "M. den Heijer published in 1995"
TL;DR: This work has identified a common mutation in MTHFR which alters a highly-conserved amino acid; the substitution occurs at a frequency of approximately 38% of unselected chromosomes and may represent an important genetic risk factor in vascular disease.
Abstract: Hyperhomocysteinaemia has been identified as a risk factor for cerebrovascular, peripheral vascular and coronary heart disease. Elevated levels of plasma homocysteine can result from genetic or nutrient-related disturbances in the trans-sulphuration or re-methylation pathways for homocysteine metabolism. 5, 10-Methylenetetrahydrofolate reductase (MTHFR) catalyzes the reduction of 5, 10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the predominant circulatory form of folate and carbon donor for the re-methylation of homocysteine to methionine. Reduced MTHFR activity with a thermolabile enzyme has been reported in patients with coronary and peripheral artery disease. We have identified a common mutation in MTHFR which alters a highly-conserved amino acid; the substitution occurs at a frequency of approximately 38% of unselected chromosomes. The mutation in the heterozygous or homozygous state correlates with reduced enzyme activity and increased thermolability in lymphocyte extracts; in vitro expression of a mutagenized cDNA containing the mutation confirms its effect on thermolability of MTHFR. Finally, individuals homozygous for the mutation have significantly elevated plasma homocysteine levels. This mutation in MTHFR may represent an important genetic risk factor in vascular disease.
5,606 citations
TL;DR: Hyperhomocysteinaemia is a common risk factor for recurrent venous thrombosis and can lead to a two-fold or three-fold increase in risk.
391 citations
TL;DR: The data demonstrate that the use of disembedded or separate versions of the questionnaire, together with variation in the case criteria can be a major explanation for variation in cut-off scores that was observed in previous studies.
Abstract: In this study we assessed the accuracy of the General Health Questionnaire in detecting psychiatric disorders in general medical out-patients. A total of 290 newly referred patients were interviewed with the Present State Examination. Prior to the interview, 112 patients completed the full GHQ-60, 100 completed the GHQ-30 and 78 completed the GHQ-12. Data from the first group were used to study the full GHQ-60, together with the GHQ-30 and and GHQ-12, when disembedded from the full questionnaire. In a comparison between the disembedded and the separate versions of the GHQ-30 and GHQ-12 we observed considerable variation in the cut-off scores where a certain sensitivity and specificity was attained. In ROC-analysis, the versions were not materially different in their discriminatory capacity (area under the curve). The use of different criteria to define a ‘case’ demonstrated that case severity was another source of increasing cut-off scores. Our data demonstrate that the use of disembedded or separate versions of the questionnaire, together with variation in the case criteria can be a major explanation for variation in cut-off scores that was observed in previous studies.
57 citations
Journal Article•
2 citations