Hyperhomocysteinemia and venous thrombosis : studies into risk and therapy

Homocysteine is a risk factor for venous thrombosis. Elevated concentrations can be treated with folic acid, vitamin B6 and vitamin B12. The main study (chapter 9) in this thesis is a randomized placebo-controlled trial in which patients with a first event of deep-vein thrombosis or pulmonary embolism are treated with above mentioned vitamins or a placebo. There was no effect of vitamin treatment on recurrent thrombosis. A case-control study is described whichs shows that elevated homocysteine concentrations are a risk factor for venous thrombosis and pulmonary embolism in elderly patients (chapter 7). Two studies deal with acidic citrate as an anticoagulant in blood collection tubes. We show that acidic citrate stabilizes homocysteine concentrations at room temperature (chapter 3) and that the homocysteine concentrations measured in blood collection tubes with acidic citrate as anticoagulant correlate well with the concentrations measured in blood tubes with EDTA as anticoagulant (chapter 4). One study compared patients on and off anticoagulant therapy. There was no influence of coumarin derivatives on plasma homocysteine concentrations (chapter 5). The endogeous thrombin potential is not different in patients with high homocysteine concentrations in comparison to patients with low homocysteine concentrations (chapter 6).LEI Universiteit LeidenKlinische epidemiologi

Onderzoek naar de ecologische achteruitgang en het herstel van Zuid-Limburgse hellingschraallandcomplexen

De Zuid-Limburgse hellingschraallanden behoren tot de meest soortenrijke graslandtypen in ons land. Ze liggen op een gradiënt van zure heischrale graslanden bovenaan de helling en basische kalkgraslanden in het middendeel van de helling. Onderaan de helling komen voedselrijkere en dus meer ruige graslandtypen voor. Het oppervlak aan goed ontwikkelde hellingschraallanden is in de 20e eeuw sterk achteruit gegaan en ook de kwaliteit ervan. Om na te gaan wat de oorzaken zijn voor de achteruitgang van flora als fauna en hoe verder herstelbeheer moet plaatsvinden, is in 2005 in het kader van OBN een vierjarig onderzoek gestart. Hieruit blijkt dat er zeker nog perspectief is voor herstel van soortenrijke hellingsschraallanden. Het beheer binnen de hellingschraallanden kan verder geoptimaliseerd worden, zodat meer afvoer van nutriënten plaatsvindt en een meer heterogene vegetatiestructuur ontstaat. Ook moet de sterke mate van versnippering en isolatie van de hellingschraallanden worden aangepakt door het vergroten en onderling verbinden van de huidige reservaten

Adult-onset autoinflammation caused by somatic mutations in UBA1:A Dutch case series of patients with VEXAS

Background: A novel autoinflammatory syndrome was recently described in male patients who harbored somatic mutations in the X-chromosomal UBA1 gene. These patients were characterized by adult-onset, treatment-refractory inflammation with fever, cytopenia, dysplastic bone marrow, vacuoles in myeloid and erythroid progenitor cells, cutaneous and pulmonary inflammation, chondritis, and vasculitis, which is abbreviated as VEXAS. Objective: This study aimed to (retrospectively) diagnose VEXAS in patients who had previously been registered as having unclassified autoinflammation. We furthermore aimed to describe clinical experiences with this multifaceted, complex disease. Methods: A systematic reanalysis of whole-exome sequencing data from a cohort of undiagnosed patients with autoinflammation from academic hospitals in The Netherlands was performed. When no sequencing data were available, targeted Sanger sequencing was applied in cases with high clinical suspicion of VEXAS. Results: A total of 12 male patients who carried mutations in UBA1 were identified. These patients presented with adult-onset (mean age 67 years, range 47-79 years) autoinflammation with systemic symptoms, elevated inflammatory parameters, and multiorgan involvement, most typically involving the skin and bone marrow. Novel features of VEXAS included interstitial nephritis, cardiac involvement, stroke, and intestinal perforation related to treatment with tocilizumab. Although many types of treatment were initiated, most patients became treatment-refractory, with a high mortality rate of 50%. Conclusion: VEXAS should be considered in the differential diagnosis of males with adult-onset autoinflammation characterized by systemic symptoms and multiorgan involvement. Early diagnosis can prevent unnecessary diagnostic procedures and provide better prognostic information and more suitable treatment options, including stem cell transplantation

Homocysteine and venous thrombosis: outline of a vitamin intervention trial.

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Heischraal grasland op Zuid-Limburgse hellingen: mogelijkheden voor versnelde ontwikkeling?

Het onderzoek is uitgevoerd op een tweetal terreinen in Zuid Limburg, te weten een hellinggrasland ten noordoosten van de Bemelerberg, en de Keerderberg. In deze gebieden is geëxperimenteerd met de behandelingen: plaggen, maaien en hooi uitleggen in verschillende combinaties. Het artikel doet verslag van de effecten van deze experimenten voor de vegetatie

Onderzoek naar de ecologische achteruitgang en het herstel van Zuid-Limburgse hellingschraallandcomplexen

Contains fulltext : 35261.pdf ( ) (Open Access)53 p

Hyperhomocysteinemie als risicofactor voor veneuze trombose.

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Oral anticoagulant treatment with coumarin derivatives does not influence plasma homocysteine concentration.

Contains fulltext : 49651.pdf (publisher's version ) (Closed access)BACKGROUND: High circulating levels of homocysteine are a risk factor for arterial and venous thrombosis. This association has been established in numerous case-control studies. In some of these studies, patients were treated with anticoagulants at the time of venapuncture. It is not clear whether homocysteine concentrations are influenced by anticoagulants. If anticoagulation does, indeed, have an effect on homocysteine levels, it might underestimate or overestimate the possible association of homocysteine levels and vascular disease. METHODS: In this study we used two different groups to investigate the effect of coumarin derivatives on homocysteine concentrations. Homocysteine levels were measured in 40 patients who were on the waiting list for orthopedic surgery and who were expected to receive prophylactic anticoagulant therapy after the operation. Measurements were taken before the operation, as well as during and after coumarin therapy. Homocysteine concentrations were also measured in a second study group consisting of 12 healthy volunteers who were treated with oral anticoagulants. RESULTS: Mean homocysteine concentrations increased by 6% (95% CI 2-10%) during the treatment with coumarin derivatives. This corresponds to a 1 mumol/L increase in homocysteine concentration. After the anticoagulant treatment period, the concentrations decreased again. We determined that this slight increase does not influence the interpretation of epidemiological studies. We also observed no significant effect of anticoagulants on homocysteine concentration after 13 weeks of treatment of healthy volunteers (decrease of 3.6%, or approximately 0.6 micromol/L; 95% CI -17.5-8.5%). CONCLUSION: We conclude that anticoagulation does not influence homocysteine concentrations to any significant degree

Measurement of total homocysteine concentrations in acidic citrate- and EDTA-containing tubes by different methods.

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Interaction between hyperhomocysteinemia, mutated methylenetetrahydrofolatereductase (MTHFR) and inherited thrombophilic factors in recurrent venous thrombosis.

Venous thrombosis is a multicausal disease involving acquired and genetic factors. In this study we investigated a possible interaction between hyperhomocysteinemia (fasting or postload) and factor V Leiden or prothrombin G20210A on the risk of recurrent venous thrombosis. We also looked at the risk due to mutations in the MTHFR-gene (C677T and A1298C). We performed a case-control study in 171 patients with a history of recurrent venous thrombosis and 461 control subjects from the general population. Hyperhomocysteinemia (fasting or 6 h after an oral methionine load) was defined as a homocysteine concentration above the 90th percentile of the distributions in the control group. The odds ratio (adjusted for age and sex) for recurrent venous thrombosis was 1.8 (95% CI: 1.1 to 3.0) for fasting hyperhomocysteinemia, 5.1 (95% CI: 3.0 to 8.6) for factor V Leiden and 1.8 (95% CI: 0.7 to 4.2) for prothrombin G20210A. We found 14 patients and 3 controls with both hyperhomocysteinemia and factor V Leiden, which yielded an odds ratio of 11.6 (95% CI: 3.2 to 42.5). We found no interaction between hyperhomocysteinemia and prothrombin G20210A. The relative risk for MTHFR 677CT was 1.6 (95% CI: 1.1 to 2.4) and for MTHFR 677TT was 1.4 (95% CI: 0.7 to 2.8). The combined risk for MTHFR 677TT and factor V Leiden was 18.7 (95% CI: 3.3 to 108). We conclude that hyperhomocysteinemia and factor V Leiden are risk factors for recurrent venous thrombosis. The risk of thrombosis appeared high for individuals who had both risk factors