Menno Huisman - Academia.edu (original) (raw)
Papers by Menno Huisman
Thrombosis and Haemostasis, 2008
Annals of internal medicine, Jan 17, 2016
The performance of different diagnostic strategies for pulmonary embolism (PE) in patient subgrou... more The performance of different diagnostic strategies for pulmonary embolism (PE) in patient subgroups is unclear. To evaluate and compare the efficiency and safety of the Wells rule with fixed or age-adjusted d-dimer testing overall and in inpatients and persons with cancer, chronic obstructive pulmonary disease, previous venous thromboembolism, delayed presentation, and age 75 years or older. MEDLINE and EMBASE from 1 January 1988 to 13 February 2016. 6 prospective studies in which the diagnostic management of PE was guided by the dichotomized Wells rule and quantitative d-dimer testing. Individual data of 7268 patients; risk of bias assessed by 2 investigators with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool. The proportion of patients in whom imaging could be withheld based on a "PE-unlikely" Wells score and a negative d-dimer test result (efficiency) was estimated using fixed (≤500 µg/L) and age-adjusted (age × 10 µg/L in patients aged >50 ...
Thromb Haemost, 2007
1. Thromb Haemost. 2008 Jan;99(1):244-5. The physician's estimation 'al... more 1. Thromb Haemost. 2008 Jan;99(1):244-5. The physician's estimation 'alternative diagnosis is less likely than pulmonary embolism' in the Wells rule is dependent on the presence of other required items. Klok FA, Zidane M, Djurabi RK, Nijkeuter M, Huisman MV. ...
Thrombosis research, Jan 15, 2016
The Wells rule is the recommended first step in the work-up of suspected deep vein thrombosis (DV... more The Wells rule is the recommended first step in the work-up of suspected deep vein thrombosis (DVT). However, it is often incorrectly used leading to an excessive number of diagnostic tests used in daily practice and diagnostic failures. A simpler objective risk stratification tool may improve adherence to the guidelines. We evaluated the diagnostic performance of the I-DVT score, which consists of four easy assessable variables: Immobilization, >3cm Difference in calve circumferences, prior Venous thromboembolism (VTE) and active malignant Tumor. We performed an observational study in 617 consecutive patients with suspected DVT. All patients were managed according to the recommended algorithm starting with the Wells rule followed by D-dimer test and/or compression ultrasonography (CUS). The I-DVT score was prospectively calculated at baseline and evaluated post-hoc. The DVT prevalence was 36%. DVT could be excluded in 13% of patients without CUS by the Wells rule and a normal D-...
Thromb Haemost, 2006
... Pulmonary embolism as a first clinical sign of occult malignancy: a prospective follow-up stu... more ... Pulmonary embolism as a first clinical sign of occult malignancy: a prospective follow-up study. van der Heiden PL, Prins MH, de Monyé W, van Strijen ML, Banga JD, Postmus PE, Ten Wolde M, Büller HR, Brandjes DP, Huisman MV; ANTELOPE study group. ...
Thrombosis and Haemostasis, Oct 1, 2003
Onn behalf of the Antelope study group DeepDeep vein thrombosis (DI 'T) and pulmonary embolism (P... more Onn behalf of the Antelope study group DeepDeep vein thrombosis (DI 'T) and pulmonary embolism (PE) are considered to be two forms of the same disease, howeverhowever it is not fully understood why some patients present with PE and others with DVT. The factor XIII (FXIII)(FXIII) and thrombin activatable fibrinolysis inhibitor (TAFI) genes encode for proteins which are involved in stabilizingstabilizing the fibrin clot and making it more lysis resistant. Polymorphisms of both genes have been reported to bebe protective against DVT Literature on the association with PE is limited and contradictory. We hypothesized thatthat the changes in clot characteristics introduced by FXIII A 34Leu and the reduced TAFI concentration associated withwith the TAFI -438 A allele may affect clot stability and thereby potentially contribute to whether a patient presentspresents with D VT or PE. We determined the frequencies of both polymorphisms in consecutive patients with a firstfirst episode of objectively demonstrated PE and in patients in whom the diagnosis PE was refuted. TheThe frequency of FXIII A 34Leu Leu in PE patients and non-PE patients was 4% and 9%. [Odds Ratio (OR) 0.5 (95%(95% CI: 0.1 to to 1.9)]. respectively. For -438 A/A TAFI genotype the frequency was 1% and 8% [OR 0.1 (95% CI:CI: 0.1)2 to 1.1) J. respectively. Subanalyses demonstrate that the TAFI -438 A allele may he associated with a lowerlower risk ofPE. Risk reduction seems to be most pronounced in young females (age less than 45 years), [OR 0.1 (95%(95% CI: 0.01 to 0.7)J, and in women using oral contraception [OR 0.1 (95% CI: 0.02 to 0.6)J.
Journal of thrombosis and haemostasis : JTH, Jan 10, 2016
To evaluate the potential association between (unprovoked) pulmonary embolism (PE) and the presen... more To evaluate the potential association between (unprovoked) pulmonary embolism (PE) and the presence and extent of coronary artery calcium (CAC) and thoracic aorta calcium (TAC). CAC and TAC derived from CT pulmonary angiography of 100 patients with PE were compared to that of 100 patients in whom PE was ruled out. Intra-observer and interobserver agreement for both TAC and CAC were excellent (ICC >0.95 for both). In patients with PE versus patients without PE, no significant differences were found in the presence of CAC or TAC (CAC 64% vs. 67%, Odds Ratio (OR) 1.0, 95%CI 0.67-1.6; TAC 46% vs. 59%, OR 1.2, 95%CI 0.80-2.1). Mean CAC and TAC scores were significantly lower in patients with PE than in patients without PE (CAC 3.4 vs. 4.9, absolute difference 1.5, 95%CI 0.2-2.8; TAC 1.1 vs. 1.8, absolute difference 0.9, 95%CI 0.2-1.2), although after correction for potential confounders this was no longer significant (p=0.10 and p=0.15). No significant differences were found in the pr...
Chest, 2016
After diagnosis of cancer-associated venous thromboembolism (VTE), guidelines recommend to consid... more After diagnosis of cancer-associated venous thromboembolism (VTE), guidelines recommend to consider continuing anticoagulant treatment until patients are cured from cancer, although the safety of stopping anticoagulant treatment after cancer is cured has never been evaluated. Cohort study in consecutive patients diagnosed with cancer-associated VTE at the Leiden University Medical Center between January 2001 and January 2010 followed for the effect of cancer treatment, occurrence of recurrent VTE, major haemorrhage and death. Of the 358 patients diagnosed with cancer-associated VTE, anticoagulant treatment was continued until death in 207 patients. In another 12 patients anticoagulant treatment was continued because of an alternative indication despite cure from cancer. Anticoagulant treatment was stopped in 50 patients for reasons other than major haemorrhage despite active cancer, in 21 patients after major haemorrhage, and in 68 patients after cure from cancer. Among these 68 patients, 10 patients were diagnosed with symptomatic recurrent VTE during a cumulative follow-up of 311 years resulting in an incidence rate (IR) of 3.2/100 PY (95%CI 1.5-5.9). Seven out of these 10 patients with recurrent VTE were also diagnosed with a cancer relapse during follow-up. In the 50 patients who stopped anticoagulant treatment despite active cancer the recurrent VTE IR was 19 per 100 PY (11 events during 59 years of follow-up; 95%CI 9.3-33). Our data support the recommendation to stop anticoagulant treatment for cancer-associated VTE in patients cured from cancer. A cancer relapse seems to be a strong risk factor for recurrent symptomatic VTE.
Thrombosis Research, Mar 1, 2009
Background: Quantitative D-Dimer tests are established methods in the non-invasive diagnostic man... more Background: Quantitative D-Dimer tests are established methods in the non-invasive diagnostic management to rule out venous thromboembolism (VTE). The diagnostic performance and the clinical efficiency different D-Dimer assays in the exclusion of pulmonary embolism (PE) have not yet been compared in a clinical outcome study. Objective: Evaluation of the efficiency and safety of excluding the diagnosis of PE with two different quantitative D-Dimer assays in consecutive patients with clinically suspected PE. Patients and Methods: We studied the VTE-failure rate of 2206 consecutive patients with an unlikely clinical probability in whom VIDAS or Tinaquant D-Dimer tests were performed. Results: The prevalence of PE in 1238 patients whose D-Dimer level was analyzed with Tinaquant assay was 11%. The VIDAS assay group consisted of 968 patients with a PE prevalence of 13%. The VIDAS assay had a sensitivity of 99.2% (95%CI; 96-N 99.9%), the Tinaquant assay of 97.3% (95%CI; 93 -99%). The negative predictive value (NPV) in the Tinaquant assay group was 99.4% (95%CI 98-99.8%) in comparison to 99.7% (95%CI 99-N 99.9%) in the VIDAS assay group. During 3 month of follow-up, there were no fatal cases of PE among patients with normal D-Dimer and unlikely clinical probability in both D-Dimer assay groups. In addition, the test efficiency of Tinaquant assay was significantly higher in comparison to VIDAS assay (52% vs 42%, p b 0.001). Conclusion: Both Tinaquant and VIDAS D-Dimer tests perform equally well in combination with an unlikely clinical probability in excluding PE. The Tinaquant test was shown to be more efficient.
Nederlands Tijdschrift Voor Geneeskunde, 2012
Two male patients aged 57 and 73 were referred to the cardiologist because of progressive dyspnoe... more Two male patients aged 57 and 73 were referred to the cardiologist because of progressive dyspnoea. In one patient, the general practitioner had previously adopted an expectative policy because of a clean chest X-ray. At presentation after 4 weeks, the patient was diagnosed with and treated for acute coronary syndrome because of minor ECG abnormalities. Additional CT scanning showed a large saddle embolus. Despite adequate treatment, the patient suffered an electrical asystole and died. The other patient underwent ECG, bicycle ergometry, MRI adenosine, echocardiography and lung function tests over a period of 5 weeks before pulmonary embolism (PE) was diagnosed. As the signs and symptoms of PE are largely non-specific, diagnostic delay is common, with risk of poor clinical outcome. PE should at least be considered whenever a patient presents with acute or worsening breathlessness, chest pain, circulatory collapse or coughing, particularly in the presence of known thrombotic risk factors or when there is no clear alternative.
Journal of intensive care medicine, 2016
Journal of Bone Joint Surgery British Volume, Mar 1, 2010
The American journal of medicine
BACKGROUND: Determination of pretest probability and D-dimer tests are the first diagnostic steps... more BACKGROUND: Determination of pretest probability and D-dimer tests are the first diagnostic steps in patients with suspected pulmonary embolism, which can be ruled out when clinical probability is unlikely and D-dimer level is normal. We evaluated the utility of D-dimer testing in patients with impaired renal function. METHODS: D-dimer tests were performed in consecutive patients with suspected pulmonary embolism and an unlikely clinical probability. Creatinine levels were assessed as clinical routine. Glomerular filtration rate was calculated using the Modification of Diet in Renal Disease formula. Correlation between D-dimer level and renal function and proportions of patients with normal D-dimer in different categories of estimated glomerular filtration rate (eGFR) were assessed. Different categories of decreasing eGFR were defined as: normal renal function (eGFR Ͼ89 mL/min), mild decrease in eGFR (eGFR 60-89 mL/min), and moderate decrease in eGFR (eGFR 30-59 mL/min). RESULTS: Creatinine levels were assessed in 351 of 385 patients (91%). D-dimer levels significantly increased in 3 categories of decreasing eGFR (P ϭ .027 and P ϭ .021 for moderate renal impairment compared with mild renal impairment and normal renal function, respectively). Normal D-dimer levels were found in 58% of patients with eGFR Ͼ89 mL/min, in 54% with eGFR 60-89 mL/min, and in 28% with eGFR 30-59 mL/min. CONCLUSIONS: The specificity of D-dimer testing in patients with suspected pulmonary embolism and decreased GFR is significantly decreased. Nonetheless, performing D-dimer tests is still useful because computed tomography scanning can be withheld in a significant proportion of these patients.
Objective-In vitro studies implicate that the low-density lipoprotein receptor (LDLR)-related pro... more Objective-In vitro studies implicate that the low-density lipoprotein receptor (LDLR)-related protein (LRP) in macrophages has a pro-atherogenic potential. In the present study, we investigated the in vivo role of macrophage specific LRP in atherogenesis independent of its role in the uptake of lipoproteins. Methods and Results-We generated macrophage-specific LRP-deficient mice on an apoE/LDLR double-deficient background. Macrophage LRP deletion did not affect plasma cholesterol and triglyceride levels, lipoprotein distribution, and blood monocyte counts. Nevertheless, macrophage LRP deficiency resulted in a 1.8-fold increase in total atherosclerotic lesion area in the aortic root of 18-week-old mice. Moreover, LRP deficiency also resulted in a relatively higher number of advanced lesions. Whereas macrophage and smooth muscle cell content did not differ between LRP-deficient mice and control littermates, a 1.7-fold increase in collagen content and 2.3-fold decrease in relative number of CD3ϩ T cells were observed in lesions from macrophage specific LRP-deficient mice. Conclusions-Our data demonstrate that independent of its role in lipoprotein uptake, absence of LRP in macrophages resulted in more advanced atherosclerosis and in lesions that contained more collagen and less CD3ϩ T cells. In contrast to previous in vitro studies, we conclude that macrophage LRP has an atheroprotective potential and may modulate the extracellular matrix in the atherosclerotic lesions. (Arterioscler Thromb Vasc Biol. 2006;26:2710-2715.)
JAMA Internal Medicine, 2015
Thrombosis Research, 2015
Thrombosis and Haemostasis, 2008
Atherosclerosis Supplements, 2001
Atherosclerosis Supplements, 2006
Low density lipoprotein receptor (LDLR), a cell-surface glycoprotein, plays an important role in ... more Low density lipoprotein receptor (LDLR), a cell-surface glycoprotein, plays an important role in maintenance of cholesterol homeostasis. LDLR mutations cause familial hypercholesterolemia (FH) in humans and LDLR deletion induces atherosclerosis in mice. Expression of LDLR is regulated by activity of sterol regulatory element-binding protein-2 (SREBP2). Peroxisome proliferator-activated receptors (PPAR), the transcription factors for regulation of energy homeostasis, metabolism of lipids and fatty acids and adipocyte differntiation, reduce atherosclerosis. Herein, we have investigated the effect of activation of PPAR on LDLR expression in mouse hepatocytes/liver. Treatment of hepatocytes with PPAR ligands, fenofibrate and troglitazone, significantly induced expression of LDLR mRNA and protein. The induction was associated with the increased uptake of LDL by cells. Fenofibrate and troglitazone also restored hepatocyte LDLR expression inhibited by LDL and 25-hydroxy-cholesterol. Mechanism studies for PPAR-induced hepatocyte LDLR expression demonstrated that PPAR induced expression and maturation of SREBP2. Feeding mice of high-fat diet suppressed LDLR expression in the liver and increased plasma total and LDL cholesterol levels. However, fenofibrate and troglitazone abolished the inhibition of LDLR expression in the liver by high-fat diet and reduced plasma total and LDL cholesterol levels. Taken together, our studies indicate that the anti-atherogenic properties of PPAR are partially attributed to the PPAR-induced LDLR expression in the liver and enhancement of the cleaxance of circulation LDL cholesterol.
Thrombosis and Haemostasis, 2008
Annals of internal medicine, Jan 17, 2016
The performance of different diagnostic strategies for pulmonary embolism (PE) in patient subgrou... more The performance of different diagnostic strategies for pulmonary embolism (PE) in patient subgroups is unclear. To evaluate and compare the efficiency and safety of the Wells rule with fixed or age-adjusted d-dimer testing overall and in inpatients and persons with cancer, chronic obstructive pulmonary disease, previous venous thromboembolism, delayed presentation, and age 75 years or older. MEDLINE and EMBASE from 1 January 1988 to 13 February 2016. 6 prospective studies in which the diagnostic management of PE was guided by the dichotomized Wells rule and quantitative d-dimer testing. Individual data of 7268 patients; risk of bias assessed by 2 investigators with the QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) tool. The proportion of patients in whom imaging could be withheld based on a "PE-unlikely" Wells score and a negative d-dimer test result (efficiency) was estimated using fixed (≤500 µg/L) and age-adjusted (age × 10 µg/L in patients aged >50 ...
Thromb Haemost, 2007
1. Thromb Haemost. 2008 Jan;99(1):244-5. The physician's estimation 'al... more 1. Thromb Haemost. 2008 Jan;99(1):244-5. The physician's estimation 'alternative diagnosis is less likely than pulmonary embolism' in the Wells rule is dependent on the presence of other required items. Klok FA, Zidane M, Djurabi RK, Nijkeuter M, Huisman MV. ...
Thrombosis research, Jan 15, 2016
The Wells rule is the recommended first step in the work-up of suspected deep vein thrombosis (DV... more The Wells rule is the recommended first step in the work-up of suspected deep vein thrombosis (DVT). However, it is often incorrectly used leading to an excessive number of diagnostic tests used in daily practice and diagnostic failures. A simpler objective risk stratification tool may improve adherence to the guidelines. We evaluated the diagnostic performance of the I-DVT score, which consists of four easy assessable variables: Immobilization, >3cm Difference in calve circumferences, prior Venous thromboembolism (VTE) and active malignant Tumor. We performed an observational study in 617 consecutive patients with suspected DVT. All patients were managed according to the recommended algorithm starting with the Wells rule followed by D-dimer test and/or compression ultrasonography (CUS). The I-DVT score was prospectively calculated at baseline and evaluated post-hoc. The DVT prevalence was 36%. DVT could be excluded in 13% of patients without CUS by the Wells rule and a normal D-...
Thromb Haemost, 2006
... Pulmonary embolism as a first clinical sign of occult malignancy: a prospective follow-up stu... more ... Pulmonary embolism as a first clinical sign of occult malignancy: a prospective follow-up study. van der Heiden PL, Prins MH, de Monyé W, van Strijen ML, Banga JD, Postmus PE, Ten Wolde M, Büller HR, Brandjes DP, Huisman MV; ANTELOPE study group. ...
Thrombosis and Haemostasis, Oct 1, 2003
Onn behalf of the Antelope study group DeepDeep vein thrombosis (DI 'T) and pulmonary embolism (P... more Onn behalf of the Antelope study group DeepDeep vein thrombosis (DI 'T) and pulmonary embolism (PE) are considered to be two forms of the same disease, howeverhowever it is not fully understood why some patients present with PE and others with DVT. The factor XIII (FXIII)(FXIII) and thrombin activatable fibrinolysis inhibitor (TAFI) genes encode for proteins which are involved in stabilizingstabilizing the fibrin clot and making it more lysis resistant. Polymorphisms of both genes have been reported to bebe protective against DVT Literature on the association with PE is limited and contradictory. We hypothesized thatthat the changes in clot characteristics introduced by FXIII A 34Leu and the reduced TAFI concentration associated withwith the TAFI -438 A allele may affect clot stability and thereby potentially contribute to whether a patient presentspresents with D VT or PE. We determined the frequencies of both polymorphisms in consecutive patients with a firstfirst episode of objectively demonstrated PE and in patients in whom the diagnosis PE was refuted. TheThe frequency of FXIII A 34Leu Leu in PE patients and non-PE patients was 4% and 9%. [Odds Ratio (OR) 0.5 (95%(95% CI: 0.1 to to 1.9)]. respectively. For -438 A/A TAFI genotype the frequency was 1% and 8% [OR 0.1 (95% CI:CI: 0.1)2 to 1.1) J. respectively. Subanalyses demonstrate that the TAFI -438 A allele may he associated with a lowerlower risk ofPE. Risk reduction seems to be most pronounced in young females (age less than 45 years), [OR 0.1 (95%(95% CI: 0.01 to 0.7)J, and in women using oral contraception [OR 0.1 (95% CI: 0.02 to 0.6)J.
Journal of thrombosis and haemostasis : JTH, Jan 10, 2016
To evaluate the potential association between (unprovoked) pulmonary embolism (PE) and the presen... more To evaluate the potential association between (unprovoked) pulmonary embolism (PE) and the presence and extent of coronary artery calcium (CAC) and thoracic aorta calcium (TAC). CAC and TAC derived from CT pulmonary angiography of 100 patients with PE were compared to that of 100 patients in whom PE was ruled out. Intra-observer and interobserver agreement for both TAC and CAC were excellent (ICC >0.95 for both). In patients with PE versus patients without PE, no significant differences were found in the presence of CAC or TAC (CAC 64% vs. 67%, Odds Ratio (OR) 1.0, 95%CI 0.67-1.6; TAC 46% vs. 59%, OR 1.2, 95%CI 0.80-2.1). Mean CAC and TAC scores were significantly lower in patients with PE than in patients without PE (CAC 3.4 vs. 4.9, absolute difference 1.5, 95%CI 0.2-2.8; TAC 1.1 vs. 1.8, absolute difference 0.9, 95%CI 0.2-1.2), although after correction for potential confounders this was no longer significant (p=0.10 and p=0.15). No significant differences were found in the pr...
Chest, 2016
After diagnosis of cancer-associated venous thromboembolism (VTE), guidelines recommend to consid... more After diagnosis of cancer-associated venous thromboembolism (VTE), guidelines recommend to consider continuing anticoagulant treatment until patients are cured from cancer, although the safety of stopping anticoagulant treatment after cancer is cured has never been evaluated. Cohort study in consecutive patients diagnosed with cancer-associated VTE at the Leiden University Medical Center between January 2001 and January 2010 followed for the effect of cancer treatment, occurrence of recurrent VTE, major haemorrhage and death. Of the 358 patients diagnosed with cancer-associated VTE, anticoagulant treatment was continued until death in 207 patients. In another 12 patients anticoagulant treatment was continued because of an alternative indication despite cure from cancer. Anticoagulant treatment was stopped in 50 patients for reasons other than major haemorrhage despite active cancer, in 21 patients after major haemorrhage, and in 68 patients after cure from cancer. Among these 68 patients, 10 patients were diagnosed with symptomatic recurrent VTE during a cumulative follow-up of 311 years resulting in an incidence rate (IR) of 3.2/100 PY (95%CI 1.5-5.9). Seven out of these 10 patients with recurrent VTE were also diagnosed with a cancer relapse during follow-up. In the 50 patients who stopped anticoagulant treatment despite active cancer the recurrent VTE IR was 19 per 100 PY (11 events during 59 years of follow-up; 95%CI 9.3-33). Our data support the recommendation to stop anticoagulant treatment for cancer-associated VTE in patients cured from cancer. A cancer relapse seems to be a strong risk factor for recurrent symptomatic VTE.
Thrombosis Research, Mar 1, 2009
Background: Quantitative D-Dimer tests are established methods in the non-invasive diagnostic man... more Background: Quantitative D-Dimer tests are established methods in the non-invasive diagnostic management to rule out venous thromboembolism (VTE). The diagnostic performance and the clinical efficiency different D-Dimer assays in the exclusion of pulmonary embolism (PE) have not yet been compared in a clinical outcome study. Objective: Evaluation of the efficiency and safety of excluding the diagnosis of PE with two different quantitative D-Dimer assays in consecutive patients with clinically suspected PE. Patients and Methods: We studied the VTE-failure rate of 2206 consecutive patients with an unlikely clinical probability in whom VIDAS or Tinaquant D-Dimer tests were performed. Results: The prevalence of PE in 1238 patients whose D-Dimer level was analyzed with Tinaquant assay was 11%. The VIDAS assay group consisted of 968 patients with a PE prevalence of 13%. The VIDAS assay had a sensitivity of 99.2% (95%CI; 96-N 99.9%), the Tinaquant assay of 97.3% (95%CI; 93 -99%). The negative predictive value (NPV) in the Tinaquant assay group was 99.4% (95%CI 98-99.8%) in comparison to 99.7% (95%CI 99-N 99.9%) in the VIDAS assay group. During 3 month of follow-up, there were no fatal cases of PE among patients with normal D-Dimer and unlikely clinical probability in both D-Dimer assay groups. In addition, the test efficiency of Tinaquant assay was significantly higher in comparison to VIDAS assay (52% vs 42%, p b 0.001). Conclusion: Both Tinaquant and VIDAS D-Dimer tests perform equally well in combination with an unlikely clinical probability in excluding PE. The Tinaquant test was shown to be more efficient.
Nederlands Tijdschrift Voor Geneeskunde, 2012
Two male patients aged 57 and 73 were referred to the cardiologist because of progressive dyspnoe... more Two male patients aged 57 and 73 were referred to the cardiologist because of progressive dyspnoea. In one patient, the general practitioner had previously adopted an expectative policy because of a clean chest X-ray. At presentation after 4 weeks, the patient was diagnosed with and treated for acute coronary syndrome because of minor ECG abnormalities. Additional CT scanning showed a large saddle embolus. Despite adequate treatment, the patient suffered an electrical asystole and died. The other patient underwent ECG, bicycle ergometry, MRI adenosine, echocardiography and lung function tests over a period of 5 weeks before pulmonary embolism (PE) was diagnosed. As the signs and symptoms of PE are largely non-specific, diagnostic delay is common, with risk of poor clinical outcome. PE should at least be considered whenever a patient presents with acute or worsening breathlessness, chest pain, circulatory collapse or coughing, particularly in the presence of known thrombotic risk factors or when there is no clear alternative.
Journal of intensive care medicine, 2016
Journal of Bone Joint Surgery British Volume, Mar 1, 2010
The American journal of medicine
BACKGROUND: Determination of pretest probability and D-dimer tests are the first diagnostic steps... more BACKGROUND: Determination of pretest probability and D-dimer tests are the first diagnostic steps in patients with suspected pulmonary embolism, which can be ruled out when clinical probability is unlikely and D-dimer level is normal. We evaluated the utility of D-dimer testing in patients with impaired renal function. METHODS: D-dimer tests were performed in consecutive patients with suspected pulmonary embolism and an unlikely clinical probability. Creatinine levels were assessed as clinical routine. Glomerular filtration rate was calculated using the Modification of Diet in Renal Disease formula. Correlation between D-dimer level and renal function and proportions of patients with normal D-dimer in different categories of estimated glomerular filtration rate (eGFR) were assessed. Different categories of decreasing eGFR were defined as: normal renal function (eGFR Ͼ89 mL/min), mild decrease in eGFR (eGFR 60-89 mL/min), and moderate decrease in eGFR (eGFR 30-59 mL/min). RESULTS: Creatinine levels were assessed in 351 of 385 patients (91%). D-dimer levels significantly increased in 3 categories of decreasing eGFR (P ϭ .027 and P ϭ .021 for moderate renal impairment compared with mild renal impairment and normal renal function, respectively). Normal D-dimer levels were found in 58% of patients with eGFR Ͼ89 mL/min, in 54% with eGFR 60-89 mL/min, and in 28% with eGFR 30-59 mL/min. CONCLUSIONS: The specificity of D-dimer testing in patients with suspected pulmonary embolism and decreased GFR is significantly decreased. Nonetheless, performing D-dimer tests is still useful because computed tomography scanning can be withheld in a significant proportion of these patients.
Objective-In vitro studies implicate that the low-density lipoprotein receptor (LDLR)-related pro... more Objective-In vitro studies implicate that the low-density lipoprotein receptor (LDLR)-related protein (LRP) in macrophages has a pro-atherogenic potential. In the present study, we investigated the in vivo role of macrophage specific LRP in atherogenesis independent of its role in the uptake of lipoproteins. Methods and Results-We generated macrophage-specific LRP-deficient mice on an apoE/LDLR double-deficient background. Macrophage LRP deletion did not affect plasma cholesterol and triglyceride levels, lipoprotein distribution, and blood monocyte counts. Nevertheless, macrophage LRP deficiency resulted in a 1.8-fold increase in total atherosclerotic lesion area in the aortic root of 18-week-old mice. Moreover, LRP deficiency also resulted in a relatively higher number of advanced lesions. Whereas macrophage and smooth muscle cell content did not differ between LRP-deficient mice and control littermates, a 1.7-fold increase in collagen content and 2.3-fold decrease in relative number of CD3ϩ T cells were observed in lesions from macrophage specific LRP-deficient mice. Conclusions-Our data demonstrate that independent of its role in lipoprotein uptake, absence of LRP in macrophages resulted in more advanced atherosclerosis and in lesions that contained more collagen and less CD3ϩ T cells. In contrast to previous in vitro studies, we conclude that macrophage LRP has an atheroprotective potential and may modulate the extracellular matrix in the atherosclerotic lesions. (Arterioscler Thromb Vasc Biol. 2006;26:2710-2715.)
JAMA Internal Medicine, 2015
Thrombosis Research, 2015
Thrombosis and Haemostasis, 2008
Atherosclerosis Supplements, 2001
Atherosclerosis Supplements, 2006
Low density lipoprotein receptor (LDLR), a cell-surface glycoprotein, plays an important role in ... more Low density lipoprotein receptor (LDLR), a cell-surface glycoprotein, plays an important role in maintenance of cholesterol homeostasis. LDLR mutations cause familial hypercholesterolemia (FH) in humans and LDLR deletion induces atherosclerosis in mice. Expression of LDLR is regulated by activity of sterol regulatory element-binding protein-2 (SREBP2). Peroxisome proliferator-activated receptors (PPAR), the transcription factors for regulation of energy homeostasis, metabolism of lipids and fatty acids and adipocyte differntiation, reduce atherosclerosis. Herein, we have investigated the effect of activation of PPAR on LDLR expression in mouse hepatocytes/liver. Treatment of hepatocytes with PPAR ligands, fenofibrate and troglitazone, significantly induced expression of LDLR mRNA and protein. The induction was associated with the increased uptake of LDL by cells. Fenofibrate and troglitazone also restored hepatocyte LDLR expression inhibited by LDL and 25-hydroxy-cholesterol. Mechanism studies for PPAR-induced hepatocyte LDLR expression demonstrated that PPAR induced expression and maturation of SREBP2. Feeding mice of high-fat diet suppressed LDLR expression in the liver and increased plasma total and LDL cholesterol levels. However, fenofibrate and troglitazone abolished the inhibition of LDLR expression in the liver by high-fat diet and reduced plasma total and LDL cholesterol levels. Taken together, our studies indicate that the anti-atherogenic properties of PPAR are partially attributed to the PPAR-induced LDLR expression in the liver and enhancement of the cleaxance of circulation LDL cholesterol.