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Biomedical subjects

M V Huisman

Publications and source records attributed to M V Huisman.

At least 19 recordsLinked to original sources

Strong decrease of high sensitivity C-reactive protein with high-dose atorvastatin in patients with type 2 diabetes mellitus.

OBJECTIVE: Statins are known to reduce CRP concentrations, but whether high doses are more effective is not known. METHODS: In a prospective double-blind multicenter study in 186 DM2 patients without manifest coronary artery disease and with dyslipidemia, the effect of a 30-week treatment with 10 and 80 mg atorvastatin or placebo on the reduction of hs-CRP levels was measured. RESULTS: Median CRP levels increased with 6.6% in the placebo group and were reduced by 15 and 47%, respectively, with atorvastatin 10 and 80 mg (P<0.001; significantly different from 10 mg atorvastatin and from placebo (P<0.001). Variation in IL-6 and plasma lipids associated for 21 and 8%, respectively, with variation in CRP levels (P<0.001 and P=0.01). Of patients with a baseline CRP level above an arbitrary threshold of 3.0 mg/l, 56% in the 80 mg atorvastatin group reached a level of less than 3.0 mg/l, versus 23% randomized to 10 mg atorvastatin (P<0.01) and 17% in the placebo group (P<0.005). CONCLUSIONS: In DM2 patients high dose atorvastatin induced a strong reduction in CRP levels. The decrease in CRP was mainly independent of effects on lipid lowering and changes in IL-6 levels. The pleiotropic effect of high-dose atorvastatin on inflammation could add to its cardioprotective effect in high-risk patients.

Aged↗

Decrease of hemostatic cardiovascular risk factors by aggressive vs. conventional atorvastatin treatment in patients with Type 2 diabetes mellitus.

BACKGROUND: Patients with Type 2 diabetes mellitus have increased levels of hemostatic risk variables for cardiovascular disease, such as fibrinogen, von Willebrand factor (VWF), factor (F)VIIa, d-dimer and plasminogen activator inhibitor-1 (PAI-1). OBJECTIVES: To evaluate the effect of aggressive vs. standard dose atorvastatin on hemostatic cardiovascular risk factors in patients with Type 2 diabetes mellitus. PATIENTS AND METHODS: The effect of 30 weeks of treatment with atorvastatin 10 and 80 mg on hemostatic cardiovascular risk factors was assessed in a randomized double-blind placebo-controlled trial on 217 patients with Type 2 diabetes mellitus and dyslipidemia. RESULTS AND CONCLUSIONS: Atorvastatin 10 and 80 mg dose-dependently reduced d-dimer (7.4% and 8.5%, respectively, P for trend = 0.004) and PAI-1 antigen levels (9.0% and 18%, respectively, P for trend = 0.021). Levels of fibrinogen, VWF, tissue-type plasminogen activator and FVIIa were not influenced by atorvastatin. In conclusion, in patients with Type 2 diabetes mellitus, atorvastatin dose-dependently improved the levels of the hemostatic risk variables d-dimer and PAI-1.

Aged↗

Impaired endothelium-dependent vasodilation in type 2 diabetes mellitus and the lack of effect of simvastatin.

OBJECTIVE: Although type 2 diabetes is recognized as an independent risk factor for cardiovascular disease and cardiovascular disease is associated with endothelial dysfunction, the influence of type 2 diabetes per se on the endothelial function is controversial. HMG-CoA-reductase inhibitors have been shown to have short-term beneficial effects on endothelial dysfunction among patients with dyslipidemia or cardiovascular disease. The effect of HMG-CoA reductase inhibitors on the endothelial function in diabetes is largely unknown. METHODS: Seventeen patients with type 2 diabetes, free of cardiovascular disease and no other cardiovascular risk factors, except for dyslipidemia, were studied together with ten healthy volunteers. The effect of 5-hydroxytryptamine, as an endothelium-dependent vasodilator, and sodium nitroprusside, as an endothelium-independent vasodilator, on the forearm blood flow was measured using venous occlusion plethysmography. RESULTS: 5-Hydroxytryptamine and sodium nitroprusside, infused in the brachial artery, caused a dose-dependent vasodilation. The vasodilator response to 5-hydroxytryptamine was significantly lower among the diabetic patients, 42 and 56%, than among the controls, 73 and 103%, at a dose of 0.3 and 0.9 ng/kg/min, respectively (P<0.05 and P<0.001). Vasodilator responses to sodium nitroprusside were comparable among the diabetic patients and controls. A 6-week treatment with simvastatin 40 mg once daily did not change the vasodilator responses to 5-hydroxytryptamine or sodium nitroprusside among the patients with diabetes. CONCLUSIONS: The results of this study indicate that the endothelial function is impaired in type 2 diabetes and is not restored after a 6-week treatment period with simvastatin 40 mg.

Case-Control Studies↗

Reduction in thrombus extension and clinical end points in patients after initial treatment for deep vein thrombosis with the fixed-dose body weight-independent low molecular weight heparin certoparin.

Low molecular weight heparin (LMWH) is effective in the treatment of acute deep vein thrombosis (DVT) in adults. This has not been demonstrated for one LMWH alone. The relationship between venographic changes due to LMWH therapy and clinical outcome in the initial treatment period has not been reported. A pooled analysis of two clinical trials was performed. The trials compared a fixed-dose, body weight-independent, subcutaneous LMWH, certoparin (8000 antifactor Xa [aXa] U twice a day [b.i.d.]), with an adjusted-dose intravenous unfractionated heparin (UFH) with respect to venographic changes expressed as Marder score and occurrence of recurrent venous thromboembolism, major bleeding, and mortality. The Marder score was 23.2 +/- 8.4 in patients randomized to LMWH (n = 299 paired phlebograms) and 23.9 +/- 8.9 in patients allocated to UFH (n = 297 paired phlebograms) at entry (2p = 0.23) and 18.9 +/- 9.7 and 20.5 +/- 9.9 at the end of the initial therapy (2p = 0.04), respectively. The composite outcome of recurrent venous thromboembolism, major bleeding, and mortality occurred less frequently during treatment with LMWH (n = 393) than it did with UFH (n = 404, 1.3% versus 5.0%, risk reduction [RR] 0.26, 95% confidence interval [CI] 0.11 to 0.63, 2p = 0.004). Single events of recurrent thromboembolism (2p = 0.12), major bleeding (2p = 0.03), and mortality (2p = 0.12) were observed less frequently with LMWH. A trend toward a lack of regression of thrombus size was observed in recurrent venous thromboembolism (2p = 0.08). Body weight-independent LMWH significantly reduces thrombus size and the incidence of composite outcome during the initial treatment of acute proximal venous thrombosis compared with adjusted dose intravenous UFH. The data indicate a relation between an unimproved Marder score and a recurrent venous thromboembolism.

Aged↗

Monitoring renal function in obese patients with type 2 diabetes mellitus in daily practice.

BACKGROUND: Endogenous creatinine clearance (GFR(24-hr)) and the Cockcroft formula (GFR(Cockcroft)) are used for the assessment of the glomerular filtration rate (GFR) in daily practice. The influence of extreme obesity in Type 2 diabetes mellitus (T2DM) on the Cockcroft formula was evaluated. METHODS: We compared GFR as calculated by GFR(Cockcroft) to GFR as determined by GFR(24-hr) in 210 patients with T2DM and normal serum creatinine levels. The influence of body mass index (BMI) on the difference between both methods was evaluated. RESULTS: GFR(Cockcroft) was an overall good predictor for GFR(24-hr), but a large individual difference between both methods was observed. A significant correlation was found between the two methods (r=0.962, p<0.001). In T2DM patients with a BMI>35 kg/m2, mean GFR(Cockcroft) was 18% greater than GFR(24-hr). For every unit BMI in this patient group the GFR(Cockcroft) increased by 7.9% relative to the GFR(24-hr). CONCLUSIONS: The major limitation of this evaluation is the lack of a gold standard for GFR measurement. This evaluation of daily practice shows the GFR estimation by the Cockcroft formula and the 24-hr creatinine clearance are in agreement, although a large individual variation was found between both methods making the interchangeability questionable. In view of the influence of BMI on the Cockcroft formula, this should not be used to estimate the GFR in T2DM patients with extreme obesity.

Body Mass Index↗

[Protocol for ambulant treatment of deep venous thrombosis in a leg: efficacious and safe in general practice].

OBJECTIVE: To evaluate a standard protocol for ambulant treatment of patients with deep venous thrombosis (DVT) in a leg with low molecular weight heparins (LMWH). DESIGN: Prospective. METHOD: A protocol was established within a regional context which provided for all patients in or around Veghel, the Netherlands, with demonstrated DVT in the period 1 March 1997-31 July 1999 to receive ambulant treatment with LMWH and oral anticoagulants. After diagnosing the treatment was started in the emergency department of the Sint Joseph Hospital in Veghel, the subsequent LMWH injectons were administered by the general practitioner in his practice. RESULTS: Of the 130 patients with demonstrated DVT, six were hospitalized because of pulmonary embolism, carcinoma or pregnancy, while 124 (95%) were eligible for ambulant treatment (56 males with a median age of 57 years (range 16-98) and 68 females with a median age of 51 years (18-89). During the acute period of LMWH treatment, none of the 124 patients developed a recurrence of thrombosis, pulmonary embolism or major haemorrhage. During 3 months' follow-up one patient developed a thrombosis in the other leg, this patient died after 2 months from disseminated carcinoma of the colon. CONCLUSION: Ambulant treatment of patients with DVT of the leg with LMWH in a daily practice setting is feasible and can be carried out effectively and safely in 95% of the patients in a regional organization.

Acute Disease↗

Recurrent venous thromboembolism: diagnosis and management.

A diagnosis of recurrent venous thromboembolism is commonly suspected by physicians in the clinical setting. Many do not realize that recurrent venous thromboembolism may mimic the first venous thromboembolic event (VTE) and that only 20 to 30% of patients who have had a first VTE actually have objective recurrent thrombotic disease. Objective testing is necessary to prevent the misdiagnosis of thrombophilia in patients and the associated exposure to prolonged anticoagulant treatment that accompanies that diagnosis. In patients with clinically suspected recurrent venous thrombosis, compression ultrasonography in a new venous segment is the preferred diagnostic approach and contrast venography is an alternative test. There is insufficient evidence to know whether D-dimer testing is an effective approach to the diagnosis of thrombophilia. In patients with suspected recurrent pulmonary embolism, the diagnostic method should begin with ventilation/perfusion lung-imaging and a complementary pulmonary angiography when the results of initial tests are equivocal. Patients with recurrent venous thromboembolism should be treated with anticoagulants for longer than 6 months but the precise period depends on the patient's risk of bleeding as a result of the treatment. Finally, there is currently a lack of evidence that risk for recurrent VTE is increased in patients with a first episode of venous thromboembolism and heterozygous factor V Leiden mutation or the G2021OA prothrombin mutation.

Fibrin Fibrinogen Degradation Products↗

Suspected pulmonary embolism: prevalence and anatomic distribution in 487 consecutive patients. Advances in New Technologies Evaluating the Localisation of Pulmonary Embolism (ANTELOPE) Group.

PURPOSE: To evaluate the prevalence and anatomic distribution of pulmonary embolism (PE) in a group of consecutive patients clinically suspected of having PE. MATERIALS AND METHODS: Four hundred eighty-seven consecutive patients clinically suspected of having PE were examined in six Dutch hospitals from May 1997 through March 1998. Patients underwent ventilation-perfusion (V-P) scintigraphy, spiral computed tomographic (CT) angiography, and/or digital subtraction pulmonary angiography according to a strict diagnostic protocol. Independent readers reviewed all of the diagnostic image studies in centralized readings. The largest pulmonary arterial branch in which PE was detected was recorded. RESULTS: The prevalence of PE was 27% (130 of 487 patients). There was a significant difference in PE size between the high-probability and nondiagnostic V-P scans: The high-probability scans tended to depict larger emboli, but they also showed small subsegmental emboli. Twenty-nine (22%) of 130 patients had subsegmental PE; 23 of these 29 patients had a high-probability V-P scan. CONCLUSION: The largest pulmonary arterial branch with PE was central or lobar in 66 (51%), segmental in 35 (27%), and isolated subsegmental in 29 (22%) patients.

Adult↗

Fixed-dose, body weight-independent subcutaneous LMW heparin versus adjusted dose unfractionated intravenous heparin in the initial treatment of proximal venous thrombosis. EASTERN Investigators.

BACKGROUND: Body weight-adjusted subcutaneous low-molecular-weight heparin (LMWH) has been proven to be at least as effective and safe as dose-adjusted intravenous unfractionated heparin (UFH) for the treatment of patients with venous thromboembolism. However, body weight-adjusted dosage of low-molecular-weight heparin may be cumbersome and could lead possibly to incorrect dosing. Therefore a fixed LMWH dose, independent of body-weight, might rationalize initial treatment for venous thromboembolism. METHODS: Patients with proven proximal deep-vein thrombosis were randomly assigned to fixed dose subcutaneous LMWH Certoparin (8,000 anti-factor Xa U b.i.d.; 265 patients) or to adjusted dose i.v. UFH (273 patients) for 12 days. Vitamin K antagonists were started between day 3 and 7 and continued for up to 6 months. The primary outcome measure was a 30 percent or greater improvement in the Marder Score, as revealed by repeated venography on day 12 (end of the initial treatment). The secondary composite outcome measure included death, recurrent venous thromboembolism and major bleeding and was assessed at day 12 and after 6 months by a blinded adjunction committee. RESULTS: The Marder score improved by 30% or more in 30.3% and 25.0% of patients assigned to LMWH (198 paired venograms) and UFH (192 paired venograms), respectively (2p = 0.26). At the end of the initial treatment, the composite outcome was observed in 4 of the 265 patients (1.5%) randomized to LMWH, as compared with 14 of the 273 patients (5.1%) randomized to UFH (2p = 0.03). At 6 months these figures were 6.8% and 12.8%, respectively (risk reduction 0.53, confidence interval 0.31-0.90, 2p = 0.02). CONCLUSION: Fixed dose subcutaneous LMWH certoparin is at least as efficacious as UFH in resolving proximal vein thrombosis.

Acute Disease↗

Clinical evaluation of a monoclonal antibody-based enzyme immunoassay for fibrin degradation products in patients with clinically suspected pulmonary embolism. ANTELOPE-Study Group.

We prospectively evaluated the diagnostic accuracy of the Fibrinostika FbDP assay in 304 consecutive patients with suspected pulmonary embolism and examined potentially useful cut-off points at which the disease can be excluded. The prevalence of pulmonary embolism was 31%. The assay generated an area under the Receiver Operating Characteristic curve of 0.79 (95% CI 0.73-0.84). A cut-off point of 0.05 microg/ml yielded a sensitivity, specificity, negative predictive value and an exclusion efficiency of 100% (95% CI 96-100), 5% (95% CI 2-9), 100% (95% CI 69-100) and 3% (95% CI 2-6), respectively. A clinically useful cut-off point seems to be 0.11 microg/ml which corresponded with a sensitivity, specificity, negative predictive value and an exclusion efficiency of 96% (95% CI 90-99), 27% (95% CI 24-28), 93% (95% CI 84-98) and 20% (95% CI 16-25), respectively. We conclude that the assay has potential clinical utility for the exclusion of pulmonary embolism, but it cannot be used as a sole test.

Adolescent↗

Use of a new monoclonal antibody-based enzyme immunoassay for soluble fibrin to exclude pulmonary embolism. ANTELOPE-Study Group.

We prospectively evaluated the diagnostic performance of a new soluble fibrin assay in 303 consecutive patients with suspected pulmonary embolism and examined potentially useful cut-off levels at which this disease can be safely excluded. In addition, the diagnostic accuracy was calculated in the subgroups of in- and outpatients. The ROC curve of the assay in the total study cohort had an area under the curve of 0.69. The cut-off level associated with a sensitivity and negative predictive value of 100% was 20 ng/ml, but the specificity was only 4%. The cut-off level with a sensitivity of 90% was 30 ng/ml, which corresponded with a specificity and negative predictive value of 27% and 86%. respectively. The diagnostic performance was comparable in the subgroups of in- and outpatients. We conclude that the soluble fibrin assay has a low diagnostic accuracy and seems unsuitable as a screening test for the exclusion of pulmonary embolism.

Adult↗

The incidence of venous thromboembolism in asymptomatic carriers of a deficiency of antithrombin, protein C, or protein S: a prospective cohort study.

Deficiencies of antithrombin, protein C, and protein S are associated with an increased risk of venous thromboembolism. The objective of this study was to prospectively assess the incidence of venous thromboembolism in nontreated asymptomatic subjects with such a deficiency. We conducted a prospective cohort study in asymptomatic family members of unselected patients who presented with a venous thromboembolic event and who were found to have a deficiency of antithrombin, protein C, or protein S. No anticoagulant prophylaxis was given to the study participants, except during risk periods for venous thromboembolism. All venous thromboembolic events were diagnosed by objective diagnostic tests. A total of 208 individuals with a mean age of 37 years (range, 15 to 79) were included in the study. A total of 611 patient observation years was obtained. Nine venous thromboembolic events occurred, resulting in an annual incidence of 1.5% (95% confidence interval [CI], 0.7 to 2.8) for the 3 deficiencies combined. Five of these events occurred spontaneously, resulting in an annual incidence of spontaneous venous thromboembolism of 0.8% (95% CI, 0.3 to 1.9). For antithrombin, protein C, and protein S deficiencies separately, this figure was 1.6%, 1.0%, and 0.4%, respectively. Thirty-four subjects experienced a total of 40 risk periods during which 4 venous thromboembolic events occurred (10% per risk period). We conclude that the use of continuous anticoagulant prophylaxis seems not warranted in asymptomatic individuals with a deficiency of antithrombin, protein C, or protein S. During risk periods for venous thromboembolism, adequate anticoagulant prophylaxis is necessary.

Adult↗

Observer dependency of the SimpliRed D-dimer assay in 81 consecutive patients with suspected pulmonary embolism.

The SimpliRed D-dimer assay is a whole blood agglutination test for the exclusion of pulmonary embolism (PE) and has been advocated as a reliable rapid bedside alternative to more time-consuming quantitative assays. However, widely differing negative predictive values (77-100%) are reported. This study assessed the intra- and interobserver variability as a possible cause for this wide accuracy range and evaluated the accuracy of the SimpliRed test in 81 consecutive patients with clinically suspected PE. Absolute D-dimer concentration was measured using the Tinaquant (Roche Diagnostics GmbH, Mannheim, Germany) assay. Every assay was immediately scored by one observer and then photographed. Photos were randomised and read twice by two other independent observers. The intraobserver reproducibility was good: kappa=0.81 and 0.73. However, we found poor interobserver reproducibility with kappa=0.47. This seems due to the fact that the SimpliRed test proved difficult to interpret in the 0.3-1.3 microg/mL plasma concentration D-dimer range, which contained 32/81 (40%) patients, 8 of whom had PE. Using pulmonary angiograms and ventilation perfusion lung scans with a concurrent spiral computed tomography scan as a gold standard (25 patients had PE), SimpliRed's accuracy to exclude PE was moderate, with negative predictive values of 0.78 and 0.84. In particular, the two observers scored the SimpliRed test as normal in 12 of 25 and 5 of 25 patients with proven PE. We conclude that SimpliRed is strongly observer-dependent. This explains the varying sensitivities for the detection of venous thromboembolism as reported in previous studies.

Fibrin Fibrinogen Degradation Products↗

Thrombophilia.

Thrombophilia is now considered a multicausal disease, with an interplay of acquired and genetic risk factors. Recent studies have shown that patients with the 20210 A prothrombin mutation display remarkably similar characteristics compared with patients with Factor V Leiden mutation. It is evident that neither the Factor V Leiden mutation nor the 20210 A prothrombin mutation is a major risk factor for myocardial infarction or stroke, unless accompanied by other classical risk factors, including diabetes mellitus, hypertension and smoking. Finally, the homozygous form of the thermolabile methylenetetrahydrofolate reductase gene, although leading to elevated homocysteine levels, seems not to represent a genetic risk factor for venous thrombosis.

Factor V↗

Incidence of venous thromboembolism in families with inherited thrombophilia.

The risk of spontaneous or risk-period related venous thromboembolism in family members of symptomatic carriers of antithrombin (AT), protein C (PC) or protein S (PS) defects, as well as of the Factor V Leiden mutation is still undefined. We performed a retrospective cohort study in family members (n = 793) of unselected patients with a documented venous thromboembolism and one of these deficiencies to make an estimate of this risk. The annual incidences of total and spontaneous venous thromboembolic events in carriers of AT, PC or PS defects (n = 181) were 1.01% and 0.40%, respectively, as compared to 0.10% and 0.04% in non-carriers, respectively (relative risks both 10.6). In carriers of Factor V Leiden (n = 224), the annual incidences of total and spontaneous venous thromboembolism were 0.28% and 0.11%, respectively, as compared to 0.09% and 0.04% in non-carriers, respectively (relative risks 2.8 and 2.5). Additional risk factors (immobilisation, surgery and trauma: oral contraceptive use; and pregnancy/ post-partum) increased the risk of thrombosis in carriers of AT, PC and PS defects as compared to non-carriers (relative risks 8.3, 6.4 and 8.2, respectively). Oral contraceptive use and pregnancy/ post-partum period increased the risk of thrombosis in carriers of Factor V Leiden to 3.3-fold and 4.2-fold, respectively, whereas other risk factors had only a minor effect. These data lend some support to the practice of screening family members of symptomatic carriers of a AT, PC and PS deficiency. For family members of symptomatic carriers of Factor V Leiden, screening does not seem to be justified except for women in fertile age.

Adolescent↗

[Acquired haemophilia A].

A 74-year-old man developed a severe bleeding disorder on the basis of acquired Factor VIII (F VIII) inhibitor. Coagulation assays showed a prolonged activated partial thromboplastin time (APTT) with a normal prothrombin time (PT);F VIII level was 0.07 IU and F VIII inhibitor level 8.8 Bethesda units (BU). At least half the cases of acquired haemophilia A are associated with pregnancy, the postpartum period or an underlying malignancy or autoimmune disease. Haemorrhagic diathesis can be severe and life-threatening. Treatment of acute haemorrhages consists of human or porcine factor VIII concentrate, activated prothrombin complex concentrate (FEIBA) or recombinant factor VIIa, depending on the antibody titre. Immunosuppressive therapy is successful in at least 60% of the patients in making the inhibitor disappear. In patients with a spontaneous haemorrhagic diathesis, a thorough medical history should be taken, coagulation assays should be performed and a specialist should be consulted.

Aged↗