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1.
Knee Surg Sports Traumatol Arthrosc ; 22(8): 1940-8, 2014 Aug.
Article in English | MEDLINE | ID: mdl-23708381

ABSTRACT

PURPOSE: Primary stability in arthrodesis of the knee can be achieved by external fixation, intramedullary nailing or plate fixation. Each method has different features and results. We present a practical algorithm for arthrodesis of the knee following a failed (infected) arthroplasty, based on our own results and a literature review. METHODS: Between 2004 and 2010, patients were included with an indication for arthrodesis after failed (revision) arthroplasty of the knee. Patients were analyzed with respect to indication, fusion method and bone contact. End-point was solid fusion. RESULTS: Twenty-six arthrodeses were performed. Eighteen patients were treated because of an infected arthroplasty. In total, ten external fixators, ten intramedullary nails and six plate fixations were applied; solid fusion was achieved in 3/10, 8/10 and 3/6, respectively. CONCLUSIONS: There is no definite answer as to which method is superior in performing an arthrodesis of the knee. Intramedullary nailing achieved the best fusion rates, but was used most in cases without--or cured--infection. Our data and the contemporary literature suggest that external fixation can be abandoned as standard fusion method, but can be of use following persisting infection. The Ilizarov circular external fixator, however, seems to render high fusion rates. Good patient selection and appropriate individual treatment are the key to a successful arthrodesis. Based upon these findings, a practical algorithm was developed.


Subject(s)
Arthrodesis/methods , Arthroplasty, Replacement, Knee/adverse effects , Knee Joint/surgery , Prosthesis-Related Infections/surgery , Aged , Arthrodesis/instrumentation , Female , Humans , Male , Prosthesis-Related Infections/etiology , Reoperation , Retrospective Studies , Treatment Failure
2.
Neth Heart J ; 21(5): 214-8, 2013 May.
Article in English | MEDLINE | ID: mdl-22311175

ABSTRACT

The arterial endothelium is a complex organ that modulates vascular tone by release of various substances to control perfusion. Endothelial function reflects vascular ageing and health. Already at the earliest stages of atherosclerosis the delicate balance between arterial constriction and relaxation is disturbed. Therefore, non-invasive assessment of endothelial function is a means to identify patients at increased cardiovascular risk, even at levels of disease that cannot be identified with classical imaging techniques that depict arterial wall and/or lumen or with functional assessment of ischaemia. Currently, there is an increasing interest in the early recognition of endothelial dysfunction to streamline and optimise preventive therapeutic measures. In this article, several methods for the assessment of endothelial function are briefly reviewed. In particular, we discuss the fast bed-side assessment of endothelial function by the reactive hyperaemia peripheral arterial tonometry (RH-PAT) method.

3.
Mycoses ; 54 Suppl 3: 22-7, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21995659

ABSTRACT

Prosthetic joint infections (PJI) are rarely due to fungal agents and if so they are mainly caused by Candida strains. This case represents a PJI caused by a multi-drug resistant Pseudallescheria apiosperma, with poor in vivo response to itraconazole and voriconazole. This case differs also by the way of infection, since the joint infection did not follow a penetrating trauma. In the majority of cases, Scedosporium extremity infections remain local in immunocompetent individuals. We report a persistent joint infection with multiple therapeutic failures, and subsequent amputation of the left leg. Detailed clinical data, patient history, treatment regime and outcome of a very long-lasting (>4 years) P. apiosperma prosthetic knee infection in an immunocompetent, 61-year-old male patient are presented with this case. The patient was finally cured by the combination of multiple and extensive surgical interventions and prolonged antifungal combination therapy with voriconazole and terbinafine.


Subject(s)
Knee Prosthesis/adverse effects , Mycoses/diagnosis , Prosthesis-Related Infections/diagnosis , Pseudallescheria , Antifungal Agents/administration & dosage , Antifungal Agents/pharmacology , Antifungal Agents/therapeutic use , Arthritis/diagnostic imaging , Arthritis/therapy , Drainage , Fistula/pathology , Humans , Hyphae/cytology , Immunocompetence , Male , Middle Aged , Mycoses/microbiology , Mycoses/therapy , Pseudallescheria/cytology , Pseudallescheria/drug effects , Pseudallescheria/isolation & purification , Radiography
4.
Scand J Rheumatol ; 40(3): 225-31, 2011 May.
Article in English | MEDLINE | ID: mdl-21261551

ABSTRACT

OBJECTIVE: Insufficient data are available on the efficacy of combined conservative interventions recommended by treatment guidelines for knee/hip osteoarthritis (OA). The aims of this observational cohort study were (i) to estimate the results of an evidence-based 12-week tailored multimodal conservative treatment protocol for patients with knee/hip OA and (ii) to identify predictors for response. METHODS: After obtaining data on previous OA-related interventions, multimodal treatment was offered to patients with knee and/or hip OA at a specialized outpatient clinic. Treatment with analgesics was tailored using a numeric rating scale (NRS) for pain, aiming for NRS ≤ 4. The following outcome measures were assessed: (i) the proportion of patients fulfilling OMERACT-OARSI (Outcome Measures in Rheumatoid Arthritis Clinical Trials/Osteoarthritis Research Society International) responder criteria and (ii) the proportion of patients with NRS pain ≤ 4 after 12 weeks. RESULTS: A total of 183 out of 299 patients was included. OMERACT-OARSI responder criteria were fulfilled at 12 weeks in 47% of patients; 39% reached NRS pain ≤ 4. The only independent predictor for response was the number of previously used non-steroidal anti-inflammatory drugs (NSAIDs). The majority of patients had not been exposed adequately to conservative treatment modalities for knee and/or hip OA in the past (81%). CONCLUSION: Evidence-based multimodal conservative treatment using a standardized protocol for knee and/or hip OA is feasible and successful in 47% of patients. In general, response could not be predicted. Basic first-line recommended conservative treatment options have not been used adequately prior to referral to secondary care in the vast majority of patients.


Subject(s)
Analgesics/therapeutic use , Dietary Supplements , Osteoarthritis, Hip/therapy , Osteoarthritis, Knee/therapy , Pain/drug therapy , Physical Therapy Modalities , Chondroitin/administration & dosage , Cohort Studies , Evidence-Based Medicine , Female , Glucosamine/administration & dosage , Humans , Male , Middle Aged , Osteoarthritis, Hip/complications , Osteoarthritis, Hip/physiopathology , Osteoarthritis, Knee/complications , Osteoarthritis, Knee/physiopathology , Pain/etiology , Pain/physiopathology , Pain Measurement , Severity of Illness Index , Surveys and Questionnaires , Treatment Outcome
5.
Neth Heart J ; 18(9): 423-9, 2010 Sep.
Article in English | MEDLINE | ID: mdl-20862237

ABSTRACT

Background. In acute myocardial infarction, thrombus aspiration prior to percutaneous coronary interventions (PCI) is often beneficial, but this approach has never been studied in patients without acute myocardial infarction. The aim of this retrospective study is to shed light on that topic based on our initial experience with manual thrombus aspiration in patients with stable or unstable angina pectoris and angiographic evidence of lesion-site thrombus. Methods. We assessed the feasibility (thrombus aspiration without predilatation) of this approach; in addition, we determined angiographic coronary flow and myocardial blush grade. Results. During 33 months in which a total of 4725 PCI were performed in our centre, manual thrombus aspiration was attempted in 14 patients with stable or unstable angina pectoris with angiographic evidence of thrombus. In nine of these 14 patients, the aspiration catheter could be advanced into the lesion without predilatation; in eight patients visible thrombus was obtained. The corrected TIMI frame count improved during the entire interventional procedure (21.1±11.2 vs. 12.8±5.9 frames; p=0.015). Myocardial blush grade, which overall improved during PCI (p<0.001), tended to show greater improvement in patients in whom thrombus aspiration could be achieved (1.6±0.9 vs. 0.7±0.5; p=0.06). Conclusions. Preliminary evidence suggests that manual thrombus aspiration may occasionally be considered in selected patients without acute myocardial infarction but with angiographic evidence of lesion-site thrombus. Nevertheless, prospective studies are required to clearly define the role of this approach in clinical practice. (Neth Heart J 2010;18:423-9.).

6.
Neth Heart J ; 18(7-8): 360-4, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20730003

ABSTRACT

Background. New-generation drug-eluting stents (DES) may solve several problems encountered with first-generation DES, but there is a lack of prospective head-to-head comparisons between new-generation DES. In addition, the outcome of regulatory trials may not perfectly reflect the outcome in 'real world' patients.Objectives. To compare the efficacy and safety of two new-generation DES in a 'real world' patient population.Methods. A prospective, randomised, single-blinded clinical trial to evaluate clinical outcome after Endeavor Resolute vs. Xience V stent implantation. The primary endpoint is target vessel failure at one-year follow-up. In addition, the study comprises a two-year and an open-label five-year follow-up. (Neth Heart J 2010;18:360-4.).

8.
J Bone Joint Surg Br ; 91(1): 31-6, 2009 Jan.
Article in English | MEDLINE | ID: mdl-19092001

ABSTRACT

We report the long-term outcome of a modified second-generation cementing technique for fixation of the acetabular component of total hip replacement. An earlier report has shown the superiority of this technique assessed by improved survival compared with first-generation cementing. The acetabular preparation involved reaming only to the subchondral plate, followed by impaction of the bone in the anchorage holes. Between 1978 and 1993, 287 total hip replacements were undertaken in 244 patients with a mean age of 65.3 years (21 to 90) using a hemispherical Weber acetabular component with this modified technique for cementing and a cemented femoral component. The survival with acetabular revision for aseptic loosening as the endpoint was 99.1% (95% confidence interval 97.9 to 100 after ten years and 85.5% (95% confidence interval 74.7 to 96.2) at 20 years. Apart from contributing to a long-lasting fixation of the component, this technique also preserved bone, facilitating revision surgery when necessary.


Subject(s)
Acetabulum/surgery , Arthroplasty, Replacement, Hip/methods , Bone Cements/therapeutic use , Cementation/methods , Hip Prosthesis/adverse effects , Acetabulum/diagnostic imaging , Adult , Aged , Aged, 80 and over , Female , Follow-Up Studies , Humans , Male , Middle Aged , Prosthesis Failure , Prosthesis-Related Infections/etiology , Radiography , Range of Motion, Articular/physiology , Treatment Outcome , Young Adult
9.
Neth Heart J ; 16(10): 344-9, 2008 Oct.
Article in English | MEDLINE | ID: mdl-18958258

ABSTRACT

Spontaneous coronary artery dissection (SCAD) is a very rare cause of acute coronary syndromes in young otherwise healthy patients with a striking predilection for the female gender. The pathological mechanism has not been fully clarified yet. However, several diseases and conditions have been associated with SCAD, such as atherosclerosis, connective tissue disorders and the peripartum episode. In this paper we present a review of the literature, discussing the possible mechanisms for SCAD, therapeutic options and prognosis. The review is illustrated with two SCAD patients who had a recurrence of a spontaneous dissection in another artery within a few days after the initial event. Because of the susceptibility to recurrent spontaneous dissections we propose at least one week of observation in hospital. Further, we will elaborate on the possible conservative and invasive treatment strategies in the acute phase of SCAD. Primary percutaneous coronary intervention remains the reperfusion strategy of choice; however, in small and medium-sized arteries with normalised flow conservative treatment is defendable. In addition, after the acute phase evaluation of possible underlying diseases is necessary, because it affects further treatment. (Neth Heart J 2008;16:344-9.).

10.
Neth Heart J ; 15(11): 382-6, 2007.
Article in English | MEDLINE | ID: mdl-18176640

ABSTRACT

BACKGROUND: Although the introduction of drugeluting stents (DES) has been associated with an impressive reduction in target vessel revascularisation, there has been concern about the safety profile. The aim of this study was to determine the incidence of stent thrombosis in real-world patients and evaluate the contribution of drug-eluting stents. METHODS: A prospective observational cohort study was conducted at a high-volume centre in Utrecht, the Netherlands. All patients who underwent a percutaneous coronary intervention (PCI) between 1 January and 31 December 2005 were evaluated. The patients were pretreated with aspirin and clopidogrel, which was continued for six months in bare metal stents (BMS) and 12 months in DES. RESULTS: In 2005, 1309 patients underwent a percutaneous coronary intervention procedure with stent implantation. After a median follow-up of nine months, 1.8% (n=23) of the patients had suffered from stent thrombosis. Two cases could be attributed to incorrect use of antiplatelet agents. In 8/23 cases, a technical reason was found such as an unrecognised dissection or stent underexpansion. The timing of stent thrombosis was acute in 1/23 patients, subacute in 20/23 patients and late in 2/23 patients. In both cases of late stent thrombosis, a BMS had been used. There were no differences in stent thrombosis rates between DES and BMS (1.4 vs. 1.9%, ns.). This is remarkable since DES were used in more complex and longer lesions. CONCLUSION: The use of DES in routine daily practice does not appear to be associated with a higher rate of stent thrombosis than BMS. (Neth Heart J 2007;15:382-6.Neth Heart J 2007;15:382-6).

11.
Neth Heart J ; 14(5): 174-176, 2006 May.
Article in English | MEDLINE | ID: mdl-25696622
13.
J Bone Joint Surg Am ; 87(7): 1522-33, 2005 Jul.
Article in English | MEDLINE | ID: mdl-15995120

ABSTRACT

BACKGROUND: The mechanisms leading to aseptic loosening of a total hip replacement are not fully understood. A fibrous tissue interface can be present around the implant. Hypothetically, component micromovements can compress this interface and cause increased fluid pressure according to biphasic models. We tested the hypothesis that compression of a fibrous membrane with or without the presence of high-density polyethylene particles leads to bone degradation. METHODS: A titanium implant was inserted in forty-five rabbit tibiae, and, after osseous integration was achieved, a fibrous tissue interface was generated. The animals were randomized to undergo a sham operation, treatment with compression of the fibrous membrane, treatment with high-density polyethylene particles, or treatment with both compression and particles. Morphometric analysis of the surrounding bone was performed on cryostat sections after Giemsa staining and staining of tartrate-resistant acid phosphatase activity. RESULTS: Forty specimens were available for analysis; five tibiae with an infection were excluded. After nine weeks, the controls showed vital bone, whereas the specimens treated with compression showed necrosis of bone and replacement of bone by cartilage in a discontinuous layer (p < 0.05 for both) but not fibrous tissue. Treatment with high-density polyethylene particles caused replacement of bone by fibrous tissue (p < 0.05) but not necrosis or cartilage formation. Compression combined with the presence of high-density polyethylene particles caused bone necrosis and loss of bone with replacement by cartilage and fibrous tissue (p < 0.05). CONCLUSIONS: In this in vivo study in rabbits, fibrous membrane compression led to bone necrosis and cartilage formation, possibly because of fluid pressure or fluid flow, whereas the presence of high-density polyethylene particles led to the loss of bone with replacement of bone by fibrous tissue. Cartilage formation may be a protective response to fluid pressure and/or fluid flow. Fibrous membrane compression may play an important role in the early stages of loosening of a total hip replacement.


Subject(s)
Biocompatible Materials/adverse effects , Connective Tissue/physiopathology , Hip Prosthesis/adverse effects , Polyethylene/adverse effects , Prosthesis Failure , Animals , Bone and Bones/physiopathology , Compressive Strength , Models, Animal , Rabbits , Titanium/adverse effects
14.
Clin Orthop Relat Res ; (419): 107-14, 2004 Feb.
Article in English | MEDLINE | ID: mdl-15021140

ABSTRACT

Between 1974 and 1989, 315 primary total hip replacements (274 patients) were done using the cemented Weber Rotation prosthesis and standardized operative technique, which was modified for the stem in 1978. After the first postoperative year, all patients had routine clinical and radiologic examinations at 2-year intervals. Twenty-one patients (22 hips) were lost to followup. At the most recent followup, 30 of 293 hips (253 patients) had been revised: 24 hips for aseptic loosening, five hips for infection, and one hip for a femoral fracture. Survivorship analyses with revision for aseptic loosening as an end point for the 315 hips showed 93% and 78% survival after 10 and 15 years, respectively. Separate survival analyses for the socket showed 99% and 89% survival after 10 and 15 years, respectively. The stem had a survival of 94% and 81%, respectively, during the same time. Survival at 15 years with radiologic evidence of loosening as an end point was 85% for the socket and 72% for the stem. The cementing technique and the design of the acetabular component significantly influenced the rate of loosening. Survivorship analyses with revision for aseptic loosening of the socket, using a modified second generation cementing technique and a hemispheric socket, showed 100% survival after 10 years and 98% after 13 years.


Subject(s)
Arthroplasty, Replacement, Hip/methods , Hip Prosthesis , Joint Instability/surgery , Prosthesis-Related Infections/diagnosis , Adult , Aged , Aged, 80 and over , Arthroplasty, Replacement, Hip/adverse effects , Cohort Studies , Confidence Intervals , Female , Follow-Up Studies , Hip Joint/physiopathology , Hip Joint/surgery , Humans , Joint Instability/etiology , Male , Middle Aged , Observer Variation , Probability , Prospective Studies , Prosthesis Design , Prosthesis Failure , Prosthesis-Related Infections/therapy , Recovery of Function , Reoperation , Time Factors , Treatment Outcome
15.
Cardiovasc Res ; 53(2): 496-501, 2002 Feb 01.
Article in English | MEDLINE | ID: mdl-11827701

ABSTRACT

OBJECTIVES: To infer the relative impact of elevated triglyceride levels and insulin resistance on endothelial dysfunction in patients with chronic hypertriglyceridemia (HTG). METHODS: Endothelial function was studied in 11 HTG patients and 16 normolipidemic controls. Cumulative-dose infusions of 5-hydroxytryptamine (5HT) and sodium nitroprusside were infused locally into the brachial artery to study endothelium-dependent and endothelium-independent vasodilation, respectively. Data of the HTG patients were dichotomized around the median of insulin resistance, calculated as HOMA-index, forming HTG groups with mild (HTG-MIR) and severe insulin resistance (HTG-SIR). RESULTS: HTG patients had higher triglyceride levels and smaller LDL particle size than controls (both P< or =0.001), whereas these parameters did not differ between both HTG groups. Insulin resistance was higher in both HTG groups than in controls (11.1 (7.0-14.5) and 4.9 (4.0-6.7) vs. 2.4 (4.9-5.2), respectively, both P<0.001). Similarly, free fatty acid levels, another indicator of insulin resistance, were highest in the HTG-SIR group, followed by those in the HTG-MIR and control group (0.7 (0.6-0.8), 0.5 (0.4-0.6) and 0.4 (0.3-0.4) mmol/l, respectively, all P<0.05). Endothelial-dependent vasodilation was similar in HTG-MIR and controls. In contrast, the response to 5HT was attenuated in the HTG-SIR group compared to controls (low and high dose by, respectively, -60 and -44%, both P<0.01), and tended to be lower than in the HTG-MIR group (-43%, P=0.068 and -41%, P=0.100, respectively). Endothelium-independent vasodilation did not differ between the three groups. CONCLUSION: These findings indicate that chronic hypertriglyceridemia per se is not associated with endothelial dysfunction. In contrast, the presence of insulin resistance, characterized by hyperinsulinemia and FFA elevation, contributes to the induction of endothelial dysfunction in chronic HTG.


Subject(s)
Endothelium, Vascular/physiopathology , Hypertriglyceridemia/physiopathology , Insulin Resistance , Nitroprusside , Serotonin , Vasodilator Agents , Adult , Case-Control Studies , Chronic Disease , Dose-Response Relationship, Drug , Fatty Acids, Nonesterified/metabolism , Humans , Hypertriglyceridemia/metabolism , Lipoproteins, LDL , Middle Aged , Particle Size , Statistics, Nonparametric
16.
Blood Coagul Fibrinolysis ; 12(8): 705-12, 2001 Dec.
Article in English | MEDLINE | ID: mdl-11734672

ABSTRACT

Hypertriglyceridemia (HTG) is an independent risk factor for cardiovascular disease (CVD). Hemostatic variables [factor VII antigen (FVIIag), factor VII coagulant activity (FVIIc), activated factor VII (FVIIa), free and endothelial-associated (EC) tissue factor pathway inhibitor (TFPI) antigen, pre- and post-heparin total TFPI activity, EC-TFPI activity, prothrombin fragment 1 + 2 (F1 + 2), fibrinogen and D-dimer] were compared between 18 HTG patients and 20 controls to investigate whether HTG is associated with alterations in the extrinsic pathway and whether such alterations create a procoagulant state, as expressed by F1 + 2 and D-dimer levels. In addition, the effects of bezafibrate therapy (6 weeks, 400 mg/day) on these variables were studied in 18 HTG patients in a double-blind, placebo-controlled, cross-over study. FVIIag, FVIIc, free TFPI and fibrinogen were significantly higher in HTG patients (by 44, 30, 45 and 31%, respectively; all P < 0.02), while FVIIa, EC-TFPIag and activity, total TFPI activities, F1 + 2 and D-dimer levels were similar in patients and controls. Bezafibrate reduced serum TG and fibrinogen levels (by 62 and 20%, respectively; both P < 0.001), whereas the other hemostatic variables were unaffected. In conclusion, the observed alterations in the extrinsic pathway in HTG are not associated with a procoagulant state. In contrast, the presence of elevated fibrinogen levels in HTG might enhance the risk for CVD. Bezafibrate therapy improved the adverse lipid profile and decreased fibrinogen levels in HTG patients.


Subject(s)
Blood Coagulation Factors/metabolism , Hypertriglyceridemia/metabolism , Thrombophilia/etiology , Adult , Antigens/drug effects , Antigens/metabolism , Bezafibrate/pharmacology , Bezafibrate/therapeutic use , Factor VII/drug effects , Factor VII/metabolism , Factor VIIa/drug effects , Factor VIIa/metabolism , Female , Hemostasis/drug effects , Humans , Hypolipidemic Agents/pharmacology , Hypolipidemic Agents/therapeutic use , Lipids/blood , Lipoproteins/blood , Lipoproteins/drug effects , Lipoproteins/metabolism , Male , Middle Aged , Thrombophilia/blood
17.
Cardiovasc Res ; 52(2): 299-305, 2001 Nov.
Article in English | MEDLINE | ID: mdl-11684078

ABSTRACT

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.


Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Endothelium, Vascular/physiopathology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Simvastatin/therapeutic use , Case-Control Studies , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/drug therapy , Dose-Response Relationship, Drug , Forearm/blood supply , Humans , Male , Middle Aged , Nitric Oxide Donors , Nitroprusside , Plethysmography , Regional Blood Flow/drug effects , Serotonin , Treatment Failure , Triglycerides/blood , Vasodilator Agents
18.
J Hypertens ; 19(4): 749-55, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11330878

ABSTRACT

OBJECTIVE: In hypertriglyceridemic patients, hypertension occurs frequently and may be associated with hyperinsulinemia and elevated plasma levels of free fatty acids (FFA). Besides the lipid-lowering effects, fibrates have been shown to reduce blood pressure in hypertensive patients. The present study was undertaken to investigate the effects of bezafibrate on hemodynamics in relation to insulin, FFA, sympathetic activity, renal sodium absorption, cyclic-GMP (cGMP) and endothelin-1 in hypertriglyceridemic patients. SUBJECTS AND METHODS: Hypertriglyceridemic patients (17) were randomized to receive in a double-blind placebo-controlled study bezafibrate or placebo for 6 weeks. At the end of both treatment periods, blood pressure and heart rate were measured automatically. Plasma insulin, FFA, aldosterone, catecholamines, cGMP, endothelin-1 levels and 24 h urine catecholamines and sodium excretion were assessed. RESULTS: Bezafibrate therapy decreased serum triglycerides (-65%, P < 0.001) and hemodynamic parameters: heart rate decreased from 69 to 66/min (P = 0.009), systolic blood pressure from 137 to 132 mmHg (P = 0.01), diastolic blood pressure from 81 to 79 mmHg (P = 0.07) and mean blood pressure from 102 to 99 mmHg (P = 0.06). Bezafibrate therapy reduced FFA and insulin (-55 and -57% respectively, both P < 0.001), while sympathetic activity and renal sodium absorption were not affected. cGMP increased (+17%, P = 0.008), whereas endothelin-1 levels tended to decrease upon bezafibrate therapy (-10%, P = 0.077) CONCLUSION: Bezafibrate reduces heart rate, blood pressure, insulin and FFA in hypertriglyceridemic patients. The hemodynamic effects cannot be attributed to changes in sympathetic activity or renal sodium absorption. Instead, based on the increase in plasma cGMP levels, the bezafibrate-induced hemodynamic effects are most likely to be caused by bezafibrate-induced improvement of endothelial function.


Subject(s)
Bezafibrate/therapeutic use , Blood Pressure/drug effects , Heart Rate/drug effects , Hypertriglyceridemia/drug therapy , Hypertriglyceridemia/physiopathology , Hypolipidemic Agents/therapeutic use , Absorption , Adult , Cyclic GMP/blood , Double-Blind Method , Fatty Acids, Nonesterified/blood , Female , Hemodynamics/drug effects , Humans , Insulin/blood , Kidney/metabolism , Lipids/blood , Male , Middle Aged , Sodium/metabolism , Sympathetic Nervous System/physiopathology
19.
Ned Tijdschr Geneeskd ; 145(12): 590-3, 2001 Mar 24.
Article in Dutch | MEDLINE | ID: mdl-11294001

ABSTRACT

Until recently, the European Union (EU) health agenda was limited to a selection of public health issues and good intentions of the Ministers of Health of the EU Member States. Lack of political will on the part of Member States to develop common policies in the fields of health care and social security is increasingly being bypassed by the political will and power of the European Parliament to initiate common action in these fields such as the Rocard report, for example, concerning the financing of health care. Furthermore, EU common market and other financial-economic regulations and policies already substantially affect the functioning of health care systems in Member States. The Netherlands' trade and professional associations should develop their organisation-specific EU strategies and policies as EU institutes, rules and culture substantially differ from national political and governmental systems; in recent years, the Dutch government has not always been successful in its approach and operations within the EU arena.


Subject(s)
European Union , Health Policy , Politics , Humans , Netherlands , Public Health/economics
20.
Arterioscler Thromb Vasc Biol ; 20(11): 2434-40, 2000 Nov.
Article in English | MEDLINE | ID: mdl-11073849

ABSTRACT

Although there is evidence that hyperlipidemia and predominance of small dense low density lipoproteins (LDLs) are associated with increased oxidative stress, the oxidation status in patients with hypertriglyceridemia (HTG) has not been studied in detail. Therefore, we studied urinary levels of F(2)-isoprostanes (8-isoprostaglandin F(2alpha) and 2,3-dinor-5,6-dihydro-8-isoprostaglandin F(2alpha)) and susceptibility of very low density lipoproteins (VLDLs) and LDLs to oxidation ex vivo in 18 patients with endogenous HTG and 20 matched control subjects. In addition, the effects of 6 weeks of bezafibrate therapy were assessed in a double-blind, placebo-controlled, crossover trial. Urinary levels of F(2)-isoprostanes were similar in the HTG and normolipidemic group. Bezafibrate caused an increase in 8-isoprostaglandin F(2alpha) (762+/-313 versus 552+/-245 ng/24 h for bezafibrate and placebo therapy, respectively; P=0.03), whereas 2,3-dinor-5, 6-dihydro-8-isoprostaglandin F(2alpha) levels tended to be increased (1714+/-761 versus 1475+/-606 ng/24 h for bezafibrate and placebo therapy, respectively; P=0.11). VLDLs and LDLs were more resistant to copper-induced oxidation in patients with HTG than in control subjects. Bezafibrate reversed the oxidation resistance to the normal range. In conclusion, these results indicate the following: (1) HTG is associated with normal in vivo oxidative stress and enhanced ex vivo resistance of lipoproteins to oxidation. (2) Bezafibrate reduces the resistance of lipoproteins to copper-induced oxidation and enhances oxidative stress in HTG patients.


Subject(s)
Bezafibrate/therapeutic use , Dinoprost/analogs & derivatives , Hypertriglyceridemia/drug therapy , Hypertriglyceridemia/metabolism , Lipoproteins/blood , Oxidative Stress/drug effects , Cholesterol, HDL/blood , Cholesterol, HDL/metabolism , Cholesterol, LDL/blood , Cholesterol, LDL/metabolism , Cross-Over Studies , Dinoprost/metabolism , Dinoprost/urine , Double-Blind Method , Female , Humans , Hypertriglyceridemia/blood , In Vitro Techniques , Lipid Metabolism , Lipids/blood , Lipoproteins/metabolism , Lipoproteins, VLDL/blood , Male , Middle Aged , Oxidation-Reduction
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