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Biomedical subjects

M Levi

Publications and source records attributed to M Levi.

At least 37 records · Page 2Linked to original sources
PubMed2004

[Extent and quality of anti-coagulation treatment with coumarin derivatives by the Dutch Thrombosis Services].

OBJECTIVE: To obtain an impression of the extent and quality of the anti-coagulation treatment with coumarin derivatives carried out by the Thrombosis Services in the Netherlands. DESIGN: Descriptive. METHOD: Data were drawn from the medical annual reports of 62 of the 63 Thrombosis Services in the Netherlands over the period 1998-2002. In 2002 the Thrombosis Services treated 325,072 patients and performed 4,469,730 INR laboratory tests. The half-yearly figures produced by the Thrombosis Services were calculated as an average percentage per year per thrombosis service and then recalculated as a percentage per year. RESULTS: Seventy-three per cent of the patients were treated for an arterial and 27% for a venous indication. Depending on the required intensity of anticoagulation a mean of 74-78% of the long-term treated patients fell within the therapeutic range and a mean of 6-10% below. The mean number of major bleedings per 100 treatment years was 1.0. A mean of 79% of the patients was treated with acenocoumarol and 21% with phenprocoumon. When acenocoumarol was used, a mean of 72-77% fell within the therapeutic range and in the case of phenprocoumon 79-82%. In the last few years the number of patients had increased due to a growing number of patients treated for atrial fibrillation. The percentages of INR within the therapeutic range were unchanged or showed a slight increase. CONCLUSION: The quality of the anticoagulation therapy with coumarin derivatives was good or acceptable.

Acenocoumarol↗
PubMed2004

[Job-sharing in postgraduate medical training: not automatically a nice duet].

Part-time work is an increasingly common phenomenon amongst medical professionals. Therefore many postgraduate training programmes for resident physicians also offer the opportunity of part-time work, which is usually in the form of an 80% full-time equivalent post. A new initiative has created the possibility of job-sharing, in which each of the participants fulfills 50% of one training position. Although the experience of the participants is mainly positive, it is unclear how this development will impact the quality of patient care and how it will affect the fulfillment of the training objectives. A more systematic evaluation of job-sharing in postgraduate medical training programmes is required to clarify these points.

Attitude of Health Personnel↗
PubMed2004

[Reasons why patients do or do not participate in clinical trials; a systemic review of the literature].

OBJECTIVE: To assess the factors that may influence a patient's consent to participate in a clinical trial. DESIGN: Systematic literature survey. METHOD: Studies on the characteristics of patients, trials, the physicians requesting informed consent and the informed consent procedures were looked for in Medline, Embase, and Cinahl. Articles published in English, German, Dutch or French in the period 1980-2002 and originating in Europe, the United States, Canada, New Zealand or Australia were included. Studies on non-adults, healthy experimental subjects or less than 30 patients were excluded. RESULTS: Thirty suitable studies were retrieved. Factors that may affect the granting of consent to participate in a clinical trial included: uncertainty of the patient, randomisation and the use of a placebo, the relationship between the person asking for informed consent and the patient, and the dissemination of information during the informed consent procedure. Since these factors are often interrelated, no single factor could be identified as decisive for participation in a clinical trial; they can influence the decision of the patient to participate in a trial in either a positive or a negative direction. CONCLUSION: Optimalization of the information concerning informed consent, the way the information is provided and the attitude of the person requesting informed consent are important and sometimes decisive factors that may determine the participation process.

Adult↗
PubMed2004

Systematic review of survival after acute mesenteric ischaemia according to disease aetiology.

BACKGROUND: Differentiation of acute mesenteric ischaemia on the basis of aetiology is of great importance because of variation in disease progression, response to treatment and outcome. The aim of this study was to analyse the published data on survival following acute mesenteric ischaemia over the past four decades in relation to disease aetiology and mode of treatment. METHOD: A systematic review of the available literature from 1966 to 2002 was performed. RESULTS: Quantitative analysis of data derived from 45 observational studies containing 3692 patients with acute mesenteric ischaemia showed that the prognosis after acute mesenteric venous thrombosis is better than that following acute arterial mesenteric ischaemia; the prognosis after mesenteric arterial embolism is better than that after arterial thrombosis or non-occlusive ischaemia; the mortality rate following surgical treatment of arterial embolism and venous thrombosis (54.1 and 32.1 per cent respectively) is less than that after surgery for arterial thrombosis and non-occlusive ischaemia (77.4 and 72.7 per cent respectively); and the overall survival after acute mesenteric ischaemia has improved over the past four decades. CONCLUSION: There are large differences in prognosis after acute mesenteric ischaemia depending on aetiology. Surgical treatment of arterial embolism has improved outcome whereas the mortality rate following surgery for arterial thrombosis and non-occlusive ischaemia remains poor.

Acute Disease↗
PubMed2004

Recombinant nematode anticoagulant protein c2, an inhibitor of tissue factor/factor VIIa, attenuates coagulation and the interleukin-10 response in human endotoxemia.

The tissue factor-factor (F)VIIa complex (TF/FVIIa) is responsible for the initiation of blood coagulation under both physiological and pathological conditions. Recombinant nematode anticoagulant protein c2 (rNAPc2) is a potent inhibitor of TF/FVIIa, mechanistically distinct from tissue factor pathway inhibitor. The first aim of this study was to elucidate the pharmacokinetics and pharmacodynamics of a single intravenous (i.v.) dose of rNAPc2. The second aim was to study its effect on endotoxin-induced coagulation and inflammation. Initially, rNAPc2 was administered to healthy volunteers in three different doses. There were no safety concerns and the pharmacokinetics were consistent with previous studies, in which rNAPc2 was administered subcutaneously. rNAPc2 elicited a dose-dependent reduction of the endogenous thrombin potential and a selective prolongation of prothrombin time. Subsequently, the effect on endotoxin-induced coagulation and inflammation was studied. The administration of rNAPc2 completely blocked the endotoxin-induced thrombin generation, as measured by plasma prothrombin fragment F1+2. The endotoxin-induced effect on fibrinolytic parameters such as plasmin-antiplasmin complexes and plasminogen activator inhibitor type 1 was not affected by rNAPc2. The administration of rNAPc2 attenuated the endotoxin-induced rise in interleukin (IL)-10, without affecting the rise in other cytokines. In conclusion, rNAPc2 is a potent inhibitor of TF/FVIIa, which was well tolerated and could safely be used intravenously in this Phase I study in healthy male volunteers. A single i.v. dose rNAPc2 completely blocked endotoxin-induced thrombin generation without affecting the fibrinolytic response. In addition, rNAPc2 attenuated the endotoxin-induced rise in IL-10, without affecting the rises in other cytokines.

Adolescent↗
PubMed2004

Beta-receptor blockade decreases elevated plasma levels of factor VIII:C in patients with deep vein thrombosis.

BACKGROUND: An elevated plasma level of factor VIII:C (FVIII:C) is a strong and dose-dependent risk factor for venous thromboembolism (VTE). The cause of elevated FVIII:C in patients with thrombophilia is as yet unknown. FVIII:C increases significantly after infusion of epinephrine, vasopressin or physical exercise. The aim of the present study was to investigate whether beta-receptor blockade will lower sustained elevated FVIII:C in patients with VTE. METHODS AND RESULTS: Two cohorts of patients with documented deep vein thrombosis and an elevated FVIII:C (>175 IU dL(-1)) and healthy volunteers, were studied. One cohort was treated with the beta-receptor blocker, whereas the other cohort served as non-treatment controls. The patient treatment group and healthy volunteers were given 40 mg propranolol, thrice daily, for 14 days. The mean baseline level of FVIII:C was 220 IU dL(-1) and 102 IU dL(-1) in patients and healthy volunteers, respectively. After 2 weeks of propranolol a significant 23% reduction of FVIII:C (- 52 IU dL(-1); 95%CI:[-65; -39]) compared with no change over time in the patient no- treatment group (-1.8 IU dL(-1); 95%CI:[-34; 30]). After discontinuation of propranolol FVIII:C returned to its initial high level. In healthy volunteers propranolol had no effect on the plasma concentration of FVIII:C. CONCLUSION: This study demonstrates that in patients with VTE a sustained elevated FVIII:C concentration can be decreased with the use of propranolol. This observation may be of potential clinical relevance, since it has been shown that each increase of 10 IU dL(-1) in FVIII:C concentration enhanced the risk of a recurrent VTE by 24%.

Adult↗
PubMed2004

Treatment effects of drotrecogin alfa (activated) in patients with severe sepsis with or without overt disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) is a serious condition associated with sepsis. Clinical management of DIC is hampered by lack of clear diagnostic criteria. The International Society on Thrombosis and Haemostasis (ISTH) has proposed a diagnostic scoring algorithm for overt DIC based on routine laboratory tests. The objective was to assess a modified version of the ISTH scoring system and determine the effect of drotrecogin alfa (activated) (DrotAA, recombinant human activated protein C) on patients with DIC. The large database from the PROWESS clinical trial in severe sepsis was retrospectively used to assess a modified ISTH scoring system. Baseline characteristics and treatment effects of DrotAA were evaluated. At baseline, 29% (454/1568) of patients had overt DIC. Overt DIC was a strong predictor of mortality, independent of APACHE II score and age. Placebo-treated patients with overt DIC had higher mortality than patients without (43 vs. 27%). DrotAA-treated patients with overt DIC had a trend towards greater relative risk reduction in mortality than patients without (29 vs. 18%, P = 0.261) but both groups had greater relative risk reduction than placebo-treated patients. Serious bleeding rates during DrotAA infusion in patients with and without overt DIC were slightly increased (P = 0.498), compared with placebo, while clinically overt thrombotic events during the 28-day period were slightly reduced (P = 0.144). Modified ISTH overt DIC scoring may be useful as an independent assessment for identifying severe sepsis patients at high risk of death with a favorable risk/benefit profile for DrotAA treatment. Patients without overt DIC also received significant treatment benefit.

Adult↗
PubMed2004

Local activation of coagulation and inhibition of fibrinolysis in the lung during ventilator associated pneumonia.

BACKGROUND: Fibrin deposition is a hallmark of pneumonia. To determine the kinetics of alterations in local coagulation and fibrinolysis in relation to ventilator associated pneumonia (VAP), a single centre prospective study of serial changes in pulmonary and systemic thrombin generation and fibrinolytic activity was conducted in patients at risk for VAP. METHODS: Non-directed bronchial lavage (NBL) was performed on alternate days in patients expected to require mechanical ventilation for more than 5 days. A total of 28 patients were studied, nine of whom developed VAP. RESULTS: In patients who developed VAP a significant increase in thrombin generation was observed in the airways, as reflected by a rise in the levels of thrombin-antithrombin complexes in NBL fluid accompanied by increases in soluble tissue factor and factor VIIa concentrations. The diagnosis of VAP was preceded by a decrease in fibrinolytic activity in NBL fluid. Indeed, before VAP was diagnosed clinically, plasminogen activator activity levels in NBL fluid gradually declined, which appeared to be caused by a sharp increase in NBL fluid levels of plasminogen activator inhibitor 1. CONCLUSION: VAP is characterised by a shift in the local haemostatic balance to the procoagulant side, which precedes the clinical diagnosis of VAP.

Blood Coagulation↗
PubMed2004

Disturbed alveolar fibrin turnover during pneumonia is restricted to the site of infection.

Severe infection is associated with profound alterations in the systemic haemostatic balance, with activation of coagulation and suppressed fibrinolysis. Within the alveolar compartment, similar disturbances have been described during pulmonary inflammation. The current authors investigated whether local haemostasis was influenced during ventilator-associated pneumonia (VAP). In five patients with unilateral VAP, bronchoalveolar lavage fluid (BALF) was obtained from both the infected site (as identified on chest radiograph) and the contralateral noninfected lung (with no clinical or radiographic abnormalities). Markers for coagulation and fibrinolysis were compared between infected and noninfected lungs. A total of 10 healthy volunteers and 10 mechanically ventilated patients without pneumonia served as controls. Strong activation of coagulation (high levels of thrombin-antithrombin complexes, soluble tissue factor and factor VIIa) was detected in BALF from infected lungs, compared with that from noninfected lungs and controls. Furthermore, in infected lungs, fibrinolysis was depressed, with high levels of plasminogen activator inhibitor type 1. In conclusion, ventilator-associated pneumonia is characterised by a hypercoagulant state at the site of infection.

Adult↗
PubMed2004

Critical bleeding in surgery: conventional therapy and new prospects.

Perioperative bleeding is one of the most frequent complications of surgery. Management of bleeding consists of local control (surgical or endoscopic hemostasis), measures to retain adequate circulation and proper transfusion procedures. In this review we will discuss various agents with a prohemostatic potential and their efficacy to reduce perioperative blood loss. Desmopressin increase the plasma concentration of Von Willebrand factor giving an augmentation of primary hemostasis. The use of recombinant activated factor VII is based on the evidence that activation of coagulation in vivo predominantly proceeds by the tissue factor/factor VII (a) pathway. Agents that exerts anti-fibrinolytic activity are aprotinin and the group of lysine analogues. The prohemostatic effect is due to inhibition of fibrinolysis and to a protective effect on platelets. Prohemostatic therapy may achieve an improvement of hemostasis, by amelioration of primary hemostasis, stimulation of fibrin formation or inhibition of fibrinolysis and seems to be effective in reducing perioperative blood loss and transfusion requirements.

Blood Loss, Surgical↗
PubMed2004

Psychological treatment of eating disorders. A review of the literature.

The aim of this study is to review the existing literature (PubMed database) on the psychological treatments for eating disorders (EDs), subdivided in individual, group and family therapies. Moreover new approaches and directions in this field are addressed. An extensive literature review is performed to identify the psychological treatment trials in anorexia nervosa (AN) and bulimia nervosa (BN) published over the past 2 decades. Eighty-two studies focused on psychotherapeutic treatment of EDs are reviewed. Only a minor part of these studies are randomised and controlled. While there is evidence of the efficacy of cognitive behavioral therapy (CBT), this is still missing for other psychotherapeutic approaches. However, there is general agreement about the importance of psychotherapy in multimodal treatments. There is still a need for a shared concept of outcome in EDs, since the efficacy of psychological treatment is greatly influenced by the definition of outcome adopted (concerning symptoms, psychosocial functioning, personality).

Anorexia Nervosa↗
PubMed2004

Quality of life and metabolic control in patients with diabetes mellitus type 1 treated by continuous subcutaneous insulin infusion or multiple daily insulin injections.

OBJECTIVE: To assess the quality of life and metabolic control in patients with diabetes mellitus type 1 on continuous subcutaneous insulin infusion (CSII) in comparison with patients on multiple daily insulin injections (MDII). RESEARCH DESIGN AND METHODS: The study included 49 patients (13 males, 36 females), aged 41.4+/-11.3 years (mean+/-SD) on CSII for >1 year and 79 patients (43 males, 36 females), aged 43.1+/-14.8 years on MDII for >1 year, from three Dutch diabetic clinics. There were no statistically significant differences in duration of diabetes, social class, level of education, marital status, smoking or recent admissions to hospital. The questionnaires used were a Diabetes Quality of Life scale adapted from the DCCT, the Diabetes Satisfaction Questionnaire (DTSQ), and the WHO Well-Being Questionnaire. HbA1c was measured with an HPLC method (reference range 4.3 to 6.1 %). RESULTS: Using two-sided t-tests no statiscally significant differences were found between the patients on CSII and MDII with respect to quality of life (version A (<30 years) 4.32+/-0.22 vs 4.20+/-0.30; version B (> or =30 years) 4.18+/-0.25 vs 4.29+/-0.28), well-being (48.59+/-9.23 vs 50.99 +/-8.70), satisfaction with treatment (5.10+/-0.69 vs 5.15+/-0.71) and HbA1c (8.14+/-1.51 vs 8.47+/-1.40). Frequency of daily blood glucose monitoring was slightly higher in CSII than in MDII patients (4.52+/-1.19 vs 3.60+/-1.47; p<0.0001). CONCLUSION: The present data indicate that patients on CSII have similar QoL based on questionnaires when compared with patients on MDII. These data suggest that in patients with less optimal control on MDII, converting the treatment strategy to CSII is not associated with decreased quality of life.

Adult↗
PubMed2003

Potential role of platelets in endothelial damage observed during treatment with cisplatin, gemcitabine, and the angiogenesis inhibitor SU5416.

PURPOSE: An increased incidence of thromboembolic events was observed during treatment with cisplatin-gemcitabine plus SU5416 (CG+SU5416), a tyrosine kinase inhibitor targeting the vascular endothelial growth factor (VEGF) receptor-1 and -2. Nine thromboembolic events occurred in eight of 19 patients. We performed an analysis of parameters of the coagulation cascade and vessel wall activation. MATERIALS AND METHODS: Markers for thrombin generation and endothelial cell activation were measured in three patients treated with CG+SU5416, two of whom developed a thromboembolic event. The results were compared with measurements in six patients treated with CG alone, and in 17 patients treated with SU5416 alone. RESULTS: During cycles 1 and 2 of treatment with CG+SU5416, a significant cycle-dependent activation of both the coagulation cascade and endothelial cells occurred, whereas platelet counts decreased. Change in platelet number had a significant negative predictive effect on soluble (s)-E-selectin levels. Significant activation of the coagulation cascade only was observed in the patients treated with CG alone, whereas in patients treated with SU5416 alone, significant endothelial cell activation was observed. CONCLUSION: We hypothesize that endothelial cells deprived of VEGF after exposure to SU5416 became activated and more susceptible to damage during treatment with CG+SU5416, which was aggravated by a transient decrease in platelets, which are, among other things, carriers of VEGF. These results suggests that VEGF, in addition to being a permeability, proliferation, and migration factor, also is a maintenance and protection factor for endothelial cells, and that platelets may have a role in maintaining vascular integrity.

Aged↗
PubMed2003

[New anticoagulants].

A large number of newly developed platelet aggregation inhibitors and anticoagulants are currently being investigated in clinical studies. Most of these new agents are targeted to haemostatic pathways that have recently been shown to be of importance in vivo and usually have a higher efficacy than the currently available anticoagulants. The new platelet aggregation inhibitors can be divided into thienopyridine derivatives (ticlopidine, clopidogrel) and glycoprotein IIb/IIIa receptor antagonists (abciximab, eptifibatide, tirofiban). The new inhibitors of fibrin synthesis can be divided into direct thrombin inhibitors (hirudine, melagatran, ximelagatran), specific factor Xa inhibitors (pentasaccharides: fondaparinux, idraparinux) and inhibitors of the tissue thromboplastin factor VIIa complex (recombinant nematode anticoagulant protein c2, inactivated factor VIIa, recombinant tissue factor pathway inhibitor). In some cases this also results in a (relatively modest) increase in the risk of bleeding. The clinical use of the new compounds is often much more convenient than that of the presently available anticoagulants.

Anticoagulants↗