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Biomedical subjects

E M van Wijk

Publications and source records attributed to E M van Wijk.

12 recordsLinked to original sources
PubMed2006

VKORC1 and CYP2C9 genotypes and phenprocoumon anticoagulation status: interaction between both genotypes affects dose requirement.

In a prospective follow-up study of the effects of VKORC1 and CYP2C9 genotypes on the anticoagulation status of patients, we assessed the CYP2C9 and the VKORC1 C1173T genotypes of patients during the initial 6 months of phenprocoumon treatment. We used linear regression models and Cox proportional hazard models to determine the effects of the VKORC1 and CYP2C9 genotypes on phenprocoumon dose requirements, overanticoagulation, and time to achieve stability. Allele frequencies of interest within the cohort (N=281) were 40.8% VKORC1 T-1173, 12.8% CYP2C9*2, and 6.9% CYP2C9*3. In patients with the VKORC1 CC genotype, carriers of a CYP2C9 polymorphism needed dosages that were nearly 30% lower than those for CYP2C9*1/*1 patients (P<0.001). In patients with a VKORC1 polymorphism, differences between carriers of a CYP2C9 polymorphism and CYP2C9*1/*1 were far smaller and largely not statistically significant. A larger part of the variability in dose requirement was explained by the VKORC1 genotype than by the CYP2C9 genotype (28.7% and 7.2%, respectively). Carriers of a combination of a CYP2C9 polymorphism and a VKORC1 polymorphism had a strongly increased risk of severe overanticoagulation (hazard ratio (HR) 7.20, P=0.002). Only carriers of a CYP2C9*2 allele had a decreased chance to achieve stability compared to CYP2C9*1/*1 patients (HR 0.61, P=0.004). In conclusion, the VKORC1 genotype modifies the effect of the CYP2C9 genotype on phenprocoumon dose requirements. A combination of polymorphisms of both genotypes is associated with a strongly increased risk of overanticoagulation, whereas delayed stabilization is mainly associated with the CYP2C9 genotype.

Aged↗
PubMed2002

Effect of VIMA with sevoflurane versus TIVA with propofol or midazolam-sufentanil on the cytokine response during CABG surgery.

BACKGROUND AND OBJECTIVE: Cardiac surgery with cardiopulmonary bypass triggers an inflammatory response involving pro-inflammatory cytokines such as tumour necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6) and interleukin 8 (IL-8). We investigated whether different anaesthetic techniques alter the pro-inflammatory cytokine response to cardiac surgery. METHODS: Thirty patients scheduled for elective coronary artery bypass grafting (CABG) surgery were randomized into three groups of 10 patients. They received either volatile inhalation induction and maintenance (Group 1) or total intravenous anaesthesia with propofol and a minimal dose sufentanil (Group 2) or a moderate dose midazolam-sufentanil (Group 3). The effect of the different anaesthetic techniques on plasma levels of TNF-alpha, IL-6 and IL-8 were examined during and after anaesthesia. RESULTS: Concentrations of TNF-alpha, and IL-8 were comparable in the three groups throughout all measurements. Before the start of cardiopulmonary bypass, IL-6 was significantly higher in Group 1 than in Group 2 (P = 0.009) or Group 3 (P = 0.030), but there were no differences between groups after cardiopulmonary bypass or postoperatively. In the three groups there was a positive correlation between aortic clamping time and serum concentrations of IL-6 (r = 0.54) and IL-8 (r = 0.62). Length of stay in intensive care was correlated with high levels of TNF-alpha (r = 0.78). CONCLUSIONS: Albeit there is difference between the volatile induction and maintenance of the anaesthesia method and the total intravenous anaesthesia technique on the pro-inflammatory cytokine response to surgical stimulation before starting of cardiopulmonary bypass, neither technique can modify the pro-inflammatory cytokine response to ischaemia-reperfusion or extracorporeal circulation.

Aged↗
PubMed2002

Dexamethasone decreases the pro- to anti-inflammatory cytokine ratio during cardiac surgery.

BACKGROUND: Cytokines regulate inflammation associated with cardiopulmonary bypass (CPB). Pro-inflammatory cytokines may cause myocardial dysfunction and haemodynamic instability after CPB, but the release of anti-inflammatory cytokines is potentially protective. We studied the effects of dexamethasone on pro- and anti-inflammatory cytokine responses during coronary artery bypass grafting surgery. METHODS: Seventeen patients were studied: nine patients received dexamethasone 100 mg before induction of anaesthesia (group 1) and eight patients acted as controls (group 2). Plasma levels of tumour necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, IL-10 and IL-4 were measured perioperatively. RESULTS: TNF-alpha and IL-8 did not increase significantly in group 1 whereas they increased in group 2 to greater than preoperative values (P<0.05). IL-6 increased in both groups, with lower values in group 1 than in group 2 (P<0.05). IL-10 increased in both groups, with higher values in group 1 (P<0.05). IL-4 did not change in group 1 but decreased in group 2 compared with pre-induction values (P<0.05). After surgery, patients in group 2 had tachycardia, hyperthermia, a greater respiratory rate and higher pulmonary artery pressure, and a longer stay in the intensive care unit. CONCLUSION: Dexamethasone given before cardiac surgery changes circulating cytokines in an anti-inflammatory direction. Postoperative outcome may be improved by inhibition of the systemic inflammatory response.

Aged↗
PubMed1990

An improved method for quantitative determination of urinary porphyrins by use of second-derivative spectroscopy.

An improved assay for quantification of urinary porphyrins by use of second-derivative spectroscopy is described. A new method for calculation of the porphyrin concentration is developed and the whole procedure is computerized. Acidified urine samples can be assayed within a few minutes by using this method. Precision and recoveries for both uro- and coproporphyrin are good. The method is presented as a very fast and accurate assay for the screening and quantification of urinary porphyrins.

Chromatography, High Pressure Liquid↗
PubMed1982

Further evaluation of an automated amidolytic factor X assay in monitoring anti-vitamin K treatment.

A mechanized factor X assay was tested in 2222 plasma samples of patients being treated with oral anticoagulants. The correlation coefficient between this assay and Thrombotest was 0.78. The therapeutic range for factor X amidolytic activity was 150 to 300 units/l. Amidolytic factor X activity and Thrombotest provide similar information about the state of anticoagulation within the same patient, including patients that are not well balanced. The ranges for factors II, VII, IX and X clotting activity in 57 patients on long-term therapy (Thrombotest within the therapeutic range between 190 and 95 s) were 80-300, 70-600, 40-420 and 50-330 units/l, respectively. The range for factor X amidolytic activity in this group of patients was 150-470 units/l.

Anticoagulants↗
PubMed1981

Optimization of a mechanized amidolytic factor-X assay; influence of reaction conditions and reagents.

We describe the effect of pH and NaCl concentration on the activation of factor X in plasma by Russell's viper venom and on the amidolytic activity of the activated enzyme towards factor Xa-sensitive chromogenic substrates. An increasing NaCl concentration results in a decrease in the activation rate of factor X by Russell's viper venom, whereas in this step no pH effect is observed. Increasing NaCl concentrations decrease the Km and Vmax for both the factor Xa-sensitive chromogenic substrates, S 2222 and S 2337. Km values were lowest between pH 7.8 and 8.6; Vmax increased with increasing pH. Comparison of NaCl and KCl in the activation step as well as in the amidolytic step shows that the observed effect is specific for Na+, not just an effect of ionic strength. No difference was detected between activation by the crude venom or its purified factor X-activating enzyme. Also, values with the substrates S 2222 or S 2337 were the same in the mechanized amidolytic factor X assay.

Anticoagulants↗
PubMed1980

Evaluation of a new chromogenic assay for factor VII and its application in patients on oral anticoagulant treatment.

A new chromogenic method has been developed and rigorously standardized for the estimation of factor VII in defibrinated diluted plasma. This method employs a mixture of CaCl2-rabbit brain thromboplastin as activator, diluted factor VII deficient plasma as source of factor X and the chromogenic substrate S2222 for the measurement of factor Xa. The chromogenic method was insensitive to cold- and kaolin-induced activation of factor VII, this in contrast to the one-stage clotting assay. Results obtained with the chromogenic method revealed good correlation with the clotting method in 33 normal subjects, in 42 patients on oral anticoagulant therapy and in five patients with severe congenital factor VII deficiency. A good correlation was also obtained with 'Thrombotest'. Comparative estimation of factor VII and of factor VII cross-reacting material in supernatants of BaCl2 adsorbed plasma of coumarin treated patients revealed that the chromogenic method does not measure decarboxy factor VII. Detailed investigations revealed a half life for decarboxy factor VII of 2.1 +/- 0.6 h.

Acenocoumarol↗
PubMed1980

Mechanized amidolytic technique for determination of factor X and factor-X antigen, and its application to patients being treated with oral anticoagulants.

We describe a mechanized chromogenic assay for factor X, the results of which correlate well with those for the one-stage clotting assays for factor X in which it is activated either via the extrinsic pathway by thromboplastin or directly by Russell's viper venom. We purified human factor X and raised monospecific antibodies to it in rabbits. We used our chromogenic assay for factor X to develop a factor-X-inhibitor neutralization assay for determination of factor-X antigen. Patients receiving oral anticoagulant treatment had significantly different factor-X activities after activation via thromboplastin or with Russell's viper venom. The concentration of factor-X antigen, although decreased, significantly exceeded factor-X clotting activity or chromogenic activity in this group of patients. Results of the chromogenic assay for factor X correlated well with results of "Thrombotest," a clotting test introduced by Owren (Lancet ii: 754, 1959) to control anticoagulant therapy. For patients taking oral anticoagulant drugs, the therapeutic range by our assay is 180 to 300 units/L.

Anticoagulants↗
PubMed1979

Spontaneous platelet aggregation in cerebrovascular disease II. Further characterisation of the platelet defect.

A group of 186 patients with Transient Ischaemic Attacks (TIA) or cerebral infarction (CI) was found to demonstrate in vitro Spontaneous Platelet Aggregation (SPA) in 39% of those studied. Of the 176 normal subjects studied the incidence on in vitro SPA was found to be 5%. Further investigation of the phenomenon of SPA revealed that: 1. it is associated with ADP-hyperaggregability, i. e. the threshold concentration to induce second wave aggregation is decreased; 2. it is dependant on the increase in pH which occurs in platelet-rich plasma stirring in an aggregometer while concurrent ADP-hyperaggregability is independant of this change in pH; 3. it is associated with malondialdehyde production and the release of endogenous 5-hydroxytryptamine; and that 4. in addition Km and Vmax values for [14c]-5HT incorporation are normal; and that 5. no gross abnormalities of the platelet membrane glycoproteins were apparent although occasionally glycoprotein III was found to be increased. This study demonstrates abnormal platelet behaviour in patients with TIA and CI where the enzyme system involved in thromboxane production is sufficiently stimulated, by stirring alone, to induce aggregation of platelets and the release reaction. Acetylsalicylic acid abolishes SPA and prolongs the bleeding time with similar characteristics as has been described for normal individuals. Plasma beta-thromboglobulin levels are significantly increased in the patients studied. However, no correlation was established with the incidence of in vitro SPA.

Adenosine Diphosphate↗