[Excellent performances of Wells' score and of the modified Wells' score for the diagnosis of proximal or distal deep venous thrombosis in outpatients or inpatients at Toulouse University Hospital: TVP-PREDICT study]. / Excellentes performances du score de Wells et du score de Wells modifié dans le diagnostic de thrombose veineuse profonde proximale ou distale chez des patients hospitalisés ou ambulatoires au CHU de Toulouse: étude TVP-PREDICT.

AIM OF THE STUDY: In order to validate a standardized strategy for the diagnosis of lower limb deep vein thrombosis (DVT) in the regional university hospital of Toulouse, we decided to study the performances of Wells' score and the modified Wells' score for the diagnosis of proximal and distal DVT. METHOD: Inpatients or outpatients referred to the vascular medicine department from April 2006 to March 2007 with suspected DVT were included prospectively and consecutively. Wells' score was determined for each patient and compared with the duplex ultrasound result. RESULTS: Two hundred and ninety-seven patients were included. The prevalence of DVT was 13.5%. The negative predictive values of Wells' score and the modified Wells' score were 99 and 97% respectively. Similar results were found for proximal or distal thrombosis. The performances of the modified Wells' score were not statistically better than those of the original score. In 48% of patients, the determination of the D-dimers would not have been contributory. In the group with low probability (70% of patients), the incidence of thrombosis was 0.6%. CONCLUSION: Wells' score and Wells' modified score have shown excellent performances. The value of the modified Wells' score is not superior and our preference, for practical reasons, goes to the original score. The widespread use of duplex ultrasound, the large proportion of patients in which D-dimers would not have been contributory and the excellent results of Wells score for patients with a low probability of DVT are encouraging arguments in favor of the development of an alternative strategy for these patients.

[Medical treatment of patients with clinical peripheral arterial disease at hospital discharge: compliance with the French guidelines and changing practices (COPART I registry)]. / Traitement médical du patient atteint d'artériopathie athéroscléreuse des membres inférieurs symptomatique à sa sortie de l'hôpital: adéquation aux recommandations et évolution des pratiques dans le temps (registre COPART I).

INTRODUCTION: Peripheral arterial disease (PAD) is a frequent and serious condition with a risk of mortality comparable to that of certain cancers. However, in France, the literature on this medical condition is scarce and data on management, incidence of complications and prognosis are lacking. PURPOSES: The COPART I registry, set up in June 2004, in the Vascular Medicine Department of the University Hospital of Toulouse, France, constitutes an observational database on hospitalized patients with PAD, in order to evaluate management, follow-up and prognosis of the patients. The aim of the present work is to compare medical prescriptions at hospital discharge, with the recent guidelines of the French High Authority of Health. METHODS: All consecutive patients with PAD, hospitalized in the Vascular Medicine Department of the University of Toulouse, between June 1, 2004 and July 31, 2006 were included. Only surviving patients were analysed. RESULTS: Four hundred patients were included in the study. As expected, the majority were male (70%). Common cardiovascular risk factors were: arterial hypertension (66.7%), dyslipidemia (58.9%), diabetes (42.9%), and smoking (27.4%). Three patients out of 10 had claudication intermittens, nearly two out of 10 patients complained of persistent pain, and four out of 10 patients had Leriche and Fontaine stage IV arteriopathy. At hospital discharge, 86.9% of the patients were taking at least one antiplatelet treatment, 71.2% a statin, 54% a renin-angiotensin-system inhibitor. Nearly 66% of the patients (65.8%) received at least one antiplatelet agent and a statin. Nearly 50% of the patients (49.4%) had the three drugs recommended by the French High Authority of Health. We observed a change in prescription practices for statins (+30%), as well as for prescription of evidence-based tri-therapy (+29%) between 2004 and 2006. CONCLUSION: Treatments prescribed at hospital discharge of patient with PAD included in the COPART I registry are in compliance with the French High Authority of Health guidelines concerning antiplatelet drugs and statins. Inhibitors of the renin-angiotensin system seem insufficiently used. However, favorable trends in medical practices between 2004 and 2006 have been observed.

[Characteristics and one-year follow-up of patients with peripheral arterial disease. Initial results of the COPART I registry]. / Caractéristiques et devenir à un an d'une cohorte de patients artériopathes hospitalisés : premiers résultats du registre COPART I.

INTRODUCTION: Almost all patients with the most severe peripheral arterial diseases (PAD) patients are hospitalised. This means that the hospital is a particularly good place to observe the characteristics and outcome of PAD patients. It is for this reason that the hospitalised patient registry (COPART I) was created. RESULTS: From June 1st 2004 to May 31st 2005, we included 187 patients surviving at hospital discharge. As expected the majority were men (68.4%). The median age was 72 (+/- 13 years). Almost one third of the PAD of patients suffered from intermittent claudication and two thir (63,6%) from permanent ischemia. A large majority of this latter group had critical limb ischemia. We found a mortality rate of 17.1% at the on year follow-up. These deaths were mainly of cardiovascular origin (9.1%). Almost 2/3 of the deaths had already occurred by six months. One patient in four undergone major or minor amputation during the follow up 2/3 of them involving major amputation. This figure rose to fou patients in ten for critical limb disease. A previous history of both major and minor amputation is strongly related with new amputations (RR = (CI: 1.2-7.5) P = 0.02). After one year of follow-up, almost four patients in ten (42.6%) with permanent ischemia had died, undergone major amputation, or suffered an MI or an IS. CONCLUSION: Peripheral arterial disease remains a severe chronic disease linked to excess mortality of cardiovascular origin. Therefore patients should be given optimal treatment.

Lack of association between ADH3 polymorphism, alcohol intake, risk factors and carotid intima-media thickness.

OBJECTIVE: We assess the relationships between alcohol dehydrogenase 3 (ADH3) polymorphism, alcohol consumption and cardiovascular risk factor levels. METHODS: In a representative population sample from Southwestern France (614 men, 567 women, age 49.7+/-8.5 years), alcohol intake was assessed by questionnaire. RESULTS: Alcohol consumption was significantly related with higher levels of total and HDL cholesterol, triglycerides, apolipoprotein A-I in men and with higher levels of HDL cholesterol in women. Also, an inverse relationship between alcohol consumption and intima-media thickness was found in men. Conversely, in both genders, no differences were found between ADH3 genotypes regarding all cardiovascular risk factors studied and carotid intima-media thickness. Also, in both genders, no significant ADH3xalcohol interaction was found for all variables, and further adjustment on age, body mass index, educational level, smoking status or after excluding subjects on hypolipidemic or antihypertensive drug treatment did not change the results. CONCLUSION: We found no interaction between the ADH3 polymorphism and alcohol intake on cardiovascular risk factor levels and atherosclerotic markers in Southwestern France.

Metabolic syndrome is associated with markers of subclinical atherosclerosis in a French population-based sample.

Metabolic syndrome (MetS) is associated with increased risk of cardiovascular disease (CVD). The relation of MetS with early stages of atherosclerosis, more important from a prevention perspective, has not been evaluated extensively. We examined the association of MetS, using WHO and NCEP definitions, with number of carotid and femoral plaques; carotid intima-media thickness (IMT); pulse wave velocity (PWV) in a random population-based sample of 1153 French adults (35-65 year). Impact of inflammatory factors (C-reactive protein and soluble intercellular adhesion molecule-1) on these parameters was also evaluated. Prevalence of MetS was 14.5 (CI: 12.3-16.0) and 17.5 (CI: 15.1-20.2)%, using NCEP and WHO definitions, respectively. MetS significantly predicted number of plaques, IMT, and PWV after adjustment for traditional risk factors (P<0.05). Inflammatory factors predicted peripheral plaques only. The risk of subclinical atherosclerosis was considerably increased with MetS (P<0.05); odds ratios ranged 1.80-2.15 with NCEP definition, and 1.48-1.97 with WHO definition. Individuals meeting both NCEP and WHO definitions had slightly greater risk of increased plaques, IMT, and PWV. MetS was strongly associated with subclinical atherosclerosis and aortic stiffness, and can be used as a surrogate marker for high CVD risk, deserving aggressive treatment.

[The anticoagulation clinic: that can not be ignored]. / La clinique des anticoagulants: un concept incontournable.

Complications linked to drug absorption are most frequently observed in the case of treatment by vitamin K antagonist (VKA), whereas 1% of the French population is treated by VKA. Despite official recommendations renewal, these complications are not decreasing. The experience of anticoagulation clinics (AC) in other countries proves their efficiency in the reduction of two-thirds of hemorragies and thrombotic recurrences. The concept of AC strictly obliged to associate therapeutic education to the patient and the calculation of the treatment dosage. Our experience started in 1998. We suggest a patient education at first during an individual consultation then during a group session. A multicentric prospective evaluation of AC vs. the conventional follow-up is on the way in France having as objectives to test the clinical efficiency and the comparison of the cost for such a supervision. In any case, important efforts have to be accomplished regarding the support of present and future antithrombotics. Their complexity of indications, supervision, and tolerance has to reinforce the rigour of therapeutic steps from the prescription to the absorption of the drug, with the possibility to appeal to the AC.

Clinical outcome and cost of hospital vs home treatment of proximal deep vein thrombosis with a low-molecular-weight heparin: the Vascular Midi-Pyrenees study.

BACKGROUND: Low-molecular-weight heparins have been shown to be effective and safe in the treatment of deep vein thrombosis. To our knowledge, there have been no direct comparisons of such treatment on an outpatient vs an inpatient basis. OBJECTIVE: To conduct a randomized, comparative, multicenter trial to evaluate the clinical outcomes and treatment costs of deep vein thrombosis in the outpatient and inpatient settings. METHODS: Two hundred one patients presenting with proximal deep vein thrombosis, without known risk factors for pulmonary embolism or hemorrhagic complications, were randomized to receive a low-molecular-weight heparin at the registered dose followed by an oral anticoagulant for up to 6 months, either in the hospital for the first 10 days followed by treatment at home (n=102) or at home from the outset (n=99). The primary clinical outcome was the incidence of venous thromboembolism recurrence, pulmonary embolism, or major bleeding. The economic analysis was performed from the point of view of the health insurance company. Total costs of the 2 management strategies were calculated to compare the cost consequences during the first 10 days. RESULTS: No differences in clinical outcome were detectable between the 2 groups. There was no increase in the rates of primary efficacy outcome in the patients treated at home vs in the hospital (3.0% vs 3.9%), while a cost reduction of 56% was demonstrated for outpatient management. CONCLUSION: For patients with proximal deep vein thrombosis and no symptoms of pulmonary embolism or increased risk of major bleeding, home treatment using a low-molecular-weight heparin is an effective, safe, and cost-saving strategy.

[Risk factors management in 5708 ambulatory patients suffering from peripheral vascular disease followed in urban practices]. / Contrôle des facteurs de risque dans une population de 5 708 artériopathes des membres inférieurs vus en médecine de ville.

STUDY OBJECTIVE: we examined the management of risk factors in patients suffering from obliterating peripheral arterial disease (OPAD), in urban medical practice. METHODS: PRISMA, ECLAT1 and APRES are surveys based on urban medicine in France. These 3 studies have allowed a compilation of data pertaining to the control of risk factors in patients suffering from one or more clinical manifestations of atherothrombosis, including cerebral vascular accident, coronary insufficiency or OPAD. The study population was divided among patients with isolated OPAD, versus OPAD associated with coronary artery disease (CAD), versus OPAD associated with cerebral vascular disease. RESULTS: a total of 5 708 patients with stable OPAD were included among the 3 studies. Risk factors were not managed in the majority of patients, including 62.6% of hypercholesterolemic patients, 71.1% of diabetics, and 77.4% of hypertensive patients. Overall, the control of risk factors was less satisfactory in patients with OPAD than in patients with CAD. Smoking (70.6% current or past smokers) remains a major risk factor in OPAD. The proportion of current smokers was significantly higher is the group with isolated OPAD than in the other 2 groups of patients (p < 0.0001). CONCLUSIONS: The control of risk factors in patients with OPAD is suboptimal, mainly because of failure to reach the therapeutic goals, rather than because of poor medical management. It is important that recent recommendations be implemented in medical practice. Awareness of the primary physicians will be key in the optimisation of treatment prescriptions and, above all, in the achievement of a higher level of clinical performance.

[Critical chronic ischemia of the limbs: organization of the management of a malignant disease]. / L'ischémie critique chronique des membres: organisation de la prise en charge d'une maladie maligne.

Chronic critical ischemia of the limbs (CCIL) typically raises the problem of early diagnosis and specialized treatment. The challenge is considerable since the incidence of CCIL is in the range of 500 to 1,000 patients/million inhabitants/year, with an incidence of major amputations from 100 to 300/million inhabitants/year. Mortality of these patients reaches 20% at 6 months and more than 80% at 10 years, which places the CCIL in the group of highly malignant oncological diseases. Despite therapeutic advances, the rate of amputations continues to progress especially in diabetics whose life expectancy is increasing due the excellent contribution of coronaropathy. Prequisites are summarized in the TASC consensus and in the discussions conducted during the creation of vascular centres: multidisciplinary teams, arteriopathy register (including CCIL and center audits), development of protocols (evaluation cost - efficiency of revascularization and medical treatments, evaluation of angiogenesis projects), collaboration between vascular centers and networks. CCIL is a malignant disease with an increasing incidence implying early and specialized care; means exist but efforts have to be made regarding their evaluation and coordination.

Non-invasive electromagnetic measurement of the peripheral pulsatile blood flow: experimental study and clinical applications.

The non-invasive electromagnetic blood flowmeter described in this paper allows us to measure pulsatile flow through a limb. The limb is placed in a magnetic field and the blood flow rate induces electromagnetic forces which are detected at the skin surface with ECG electrodes (Faraday's law). A special computer technique is necessary to isolate the signal from artefacts (local ECG, BCG, EMG). In vitro calibration is performed using a circulatory model and in vivo using mongrel dogs. Its validity is assessed by comparing the results with the responses obtained from the invasive electromagnetic flowmeter. Sources of error in the measurement such as blood composition (Na+, K+), haematocrit (45% to 29%), and venous flow are reported here. The results indicate that the method is reliable, easy to utilise and offers a unique non-invasive way of measuring true pulsatile blood flow rate in humans. Various clinical applications are discussed for possible use of the device.

Incidence and prognosis of cancer associated with bilateral venous thrombosis: a prospective study of 103 patients.

BACKGROUND: A strong association between bilateral deep vein thrombosis (DVT) and cancer had been found in one retrospective study. To confirm this finding, consecutive patients with an objective diagnosis of bilateral DVT were followed over 12 months. PATIENTS AND METHODS: One-hundred and three patients, hospitalized for bilateral DVT, were included in the study. Twenty-six patients (25.2%) were already known to have a cancer, 26 (25.2%) had a previous history of venous thromboembolic disease, 44 (42.7%) had a symptomatic pulmonary embolism. The patients were scheduled to be prospectively followed up at 3, 6 and 12 months as outpatients. Information on recurrence, evidence of a new overt cancer and the cause of death were recorded for all patients. RESULTS: A new cancer was diagnosed in 20 (26%) of the 77 patients without known cancer at admission. The risk of cancer was significantly more important in idiopathic thrombosis than in patients with secondary thrombosis (40.5% vs. 12.5%; odds ratio 4.8, 95% confidence interval 1.4, 18.8). Seventy percent of the cancers discovered had already spread. Age, gender, presence of pulmonary embolism, recurrence and location of the thrombosis were not statistically associated with the risk of cancer. The 1-year survival rates of patients with a previously known cancer and patients with a newly discovered cancer were, respectively, 26% and 35% (P = 0.33). CONCLUSIONS: Bilateral DVT is a significant risk indicator of malignancy. Cancer is present in 45% of patients with bilateral DVT and is associated with a poor prognosis.

Carotid intima-media thickness and coronary heart disease risk factors in a low-risk population.

OBJECTIVE: Coronary heart disease (CHD) risk factors have been consistently related to an increase in carotid intima-media thickness (IMT) in selected populations. However, few studies were population-based and furthermore little attention has been given to the influence of CHD risk factors on IMT in low-risk populations for CHD. DESIGN: We examined the association between carotid IMT and CHD risk factors in a large (n = 1013) and representative sample of middle-aged men and women in one of the European populations with the lowest CHD risk. METHODS: High-resolution B-mode ultrasonography of the common carotid arteries was performed. RESULTS: Age, smoking (not significant in women), body mass index, waist to hip ratio, systolic (SBP) and diastolic blood pressure, alcohol consumption, total and low-density lipoprotein cholesterol, triglycerides, glycaemia, fibrinogen (not significant in women), haematocrit (not significant in men) and insulin (not significant in women) were positively and significantly associated with mean IMT. High-density lipoprotein (HDL) cholesterol (not significant in women) was negatively and significantly associated with mean IMT. In a subsample of 355 men, IMT was not associated with angiotensin I-converting enzyme gene polymorphism. Multivariate analyses showed, in men, independent associations between mean IMT (0.61+/-0.11 mm) and age, pack-years, SBP, HDL cholesterol, alcohol and the interaction between age and alcohol. In women, only age and SBP were independently associated with mean IMT (0.58+/-0.09 mm). CONCLUSIONS: We found thinner IMT than those found in high-risk populations, suggesting that an increased IMT might reflect local atherosclerosis. Protective factors such as HDL cholesterol or regular and moderate alcohol consumption are probably important determinants of the early stages of atherosclerosis in these low-risk populations.

Dermatan sulfate is a more potent inhibitor of clot-bound thrombin than unfractionated and low molecular weight heparins.

Clot-bound thrombin proteolyses fibrinogen and amplifies the coagulation cascade at its close vicinity, thereby ensuring the growth of fibrin-rich thrombus. The present study compares the ability of various glycosaminoglycans (GAGs) to inhibit these 2 properties. Unfractionated heparin (UH), 3 low molecular weight heparins (LMWHs) with increasing antifactor Xa/antifactor IIa ratio, the synthetic pentasaccharide (PS), devoid of antifactor IIa activity, and dermatan sulfate (DS), a catalyst of thrombin inhibition by heparin cofactor II, were selected on the basis of their different properties. Proteolysis of fibrinogen by clot-bound thrombin was evaluated by measuring fibrinopeptide A (FPA) generation after an incubation of standardized washed clots in plasma for 120 min in absence or in presence of increasing concentrations of heparins or of DS. The results were compared to those obtained when free alpha-thrombin (0.4 nM) was added to plasma in the same experimental conditions. On the basis of equivalent antithrombin units, UH and LMWHs gave identical results. To inhibit by 70% fibrinogen proteolysis induced by clot-bound thrombin (IC 70), 5- to 9-fold higher concentrations of UH or of LMWHs were required in comparison with those required to inhibit free thrombin. For DS, only a 1.3 times higher concentration was required. PS (final concentration 1 anti Xa U.ml-1) was devoid of any inhibitory effect. The amplification of the coagulation cascade induced by clot-bound thrombin was evaluated by measuring the shortening of whole blood clotting time (WBCT) resulting from the incubation of washed clots in native blood. In absence of GAG, clot-bound thrombin reduced WBCT from 18 +/- 2 min to 9 +/- 1 min.(ABSTRACT TRUNCATED AT 250 WORDS)

D-Dimers, thrombin antithrombin III complexes and prothrombin fragments 1+2: diagnostic value in clinically suspected deep vein thrombosis.

This study was performed to determine the accuracy of D-Dimer fibrin derivatives, thrombin-antithrombin III (TAT) complexes and prothrombin fragments 1 + 2 (F 1 + 2) determinations for the diagnosis of deep vein thrombosis (DVT). One hundred and sixteen consecutive patients referred to the angiology unit of our hospital for a clinically suspected DVT were investigated. They were submitted to mercury strain gauge plethysmography and to ultrasonic duplex scanning examination; in cases of inconclusive results or of proximal DVT (n = 35), an ascending phlebography was performed. After these investigations were completed, the diagnosis of DVT was confirmed in 34 and excluded in 82. One half of the patients were already under anticoagulant therapy at the time of investigation. The 3 biological markers were assayed using commercially available ELISA techniques and the D-Dimer was also assayed with a fast latex method. The normal distribution of these markers was established in 40 healthy blood donors. The most accurate assay for the diagnosis of DVT was the D-Dimer ELISA which had both a high sensitivity (94%) and a high negative predictive value (95%). The D-Dimer latex, TAT complexes and F 1 + 2 were far less sensitive and provided negative predictive values which ranged between 78 and 85%. In spite of positive and significant correlations between the levels of the 3 markers, their association did not improve their overall accuracy for detecting DVT. Therefore, with the exception of the D-Dimer ELISA, these markers were of little value for the diagnosis of DVT in this specific population.

Influence of long term oral anticoagulants upon prothrombin fragment 1 + 2, thrombin-antithrombin III complex and D-Dimer levels in patients affected by proximal deep vein thrombosis.

We have investigated the influence of long term oral anticoagulants (OAC) upon the plasma levels of prothrombin fragment 1 + 2 (F1 + 2), of thrombin-antithrombin III complexes (TAT) and of D-Dimer in 20 patients affected by a proximal deep vein thrombosis (DVT) diagnosed by ultrasonic duplex scanning. Patients (63 +/- 17 years, mean +/- SD) were sampled at the beginning of the OAC treatment (day 1), which was started 1 to 6 days after diagnosis confirmation and full heparinization, and then 8, 35 and 92 days after. The results were compared to those obtained in a blood donor population (39 +/- 10 years) and to an age-matched healthy population (63 +/- 19 years). The mean INR determined on days 8, 35 and 92 were almost identical (2.8 +/- 0.7, 2.9 +/- 0.9 and 2.8 +/- 0.6 respectively). In contrast, highly significant variations of the three markers were recorded during the observation period. Eight days after the beginning of OAC, increased levels of TAT complexes were associated with subnormal levels of F1 + 2 suggesting persistence of a hypercoagulable state. On the further sampling times, TAT complexes were in the normal range while F1 + 2 were far below the normal range. Between day 1 and day 92, the levels of D-Dimer continuously decreased reflecting a long-term fibrinolytic process. This study clearly indicates that high INR are not systematically associated with very low F1 + 2 levels, particularly in the acute phase of thrombosis.(ABSTRACT TRUNCATED AT 250 WORDS)

D-dimer test and diagnosis of deep vein thrombosis: a comparative study of 7 assays.

The current D-Dimer ELISA methods provide high sensitivity and negative predictive value for the diagnosis of deep vein thrombosis but these methods are not suitable for emergency or for individual determination. We have evaluated the performance of 3 newly available fast D-Dimer assays (Vidas D-Di, BioMérieux; Instant IA D-Di, Stago; Nycocard D-Dimer, Nycomed) in comparison with 3 classic ELISA methods (Stago, Organon, Behring) and a Latex agglutination technique (Stago). One-hundred-and-seventy-one patients suspected of presenting a first episode of deep vein thrombosis were investigated. A deep vein thrombosis was detected in 75 patients (43.8%) by ultrasonic duplex scanning of the lower limbs; in 11 of them the thrombi were distal and very limited in size (< 2 cm). We compared the performance of the tests by calculating their sensitivity, specificity, positive and negative predictive value for different cut-off levels and by calculating the area under ROC curves. The concordance of the different methods was evaluated by calculating the kappa coefficient. The performances of the 3 classic ELISA and of the Vidas D-Di were comparable and kappa coefficients indicated a good concordance between the results provided by these assays. Their sensitivity slightly declined for detection of the very small thrombi. Instant IA D-Di had a non-significantly lower sensitivity and negative predictive value than the 4 previous assays; however its performance was excellent for out-patients. As expected, the Latex assay had too low a sensitivity and negative predictive value to be recommended. In our hands, Nycocard D-Dimer also exhibited low sensitivity and negative predictive value, which were significantly improved when the plasma samples were tested by the manufacturer. Thus significant progress has been made, allowing clinical studies to be planned to compare the safety and cost-effectiveness of D-Dimer strategy to those of the conventional methods for the diagnosis of venous thrombosis.

Predicting daily maintenance dose of fluindione, an oral anticoagulant drug.

Due to large inter-individual variations, the dose of vitamin K antagonist required to target the desired hypocoagulability is hardly predictible for a given patient, and the time needed to reach therapeutic equilibrium may be excessively long. This work reports on a simple method for predicting the daily maintenance dose of fluindione after the third intake. In a first step, 37 patients were delivered 20 mg of fluindione once a day, at 6 p.m. for 3 consecutive days. On the morning of the 4th day an INR was performed. During the following days the dose was adjusted to target an INR between 2 and 3. There was a good correlation (r = 0.83, p < 0.001) between the INR performed on the morning of day 4 and the daily maintenance dose determined later by successive approximations. This allowed us to write a decisional algorithm to predict the effective maintenance dose of fluindione from the INR performed on day 4. The usefulness and the safety of this approach was tested in a second prospective study on 46 patients receiving fluindione according to the same initial scheme. The predicted dose was compared to the effective dose soon after having reached the equilibrium, then 30 and 90 days after. To within 5 mg (one quarter of a tablet), the predicted dose was the effective dose in 98%, 86% and 81% of the patients at the 3 times respectively. The mean time needed to reach the therapeutic equilibrium was reduced from 13 days in the first study to 6 days in the second study. No hemorrhagic complication occurred. Thus the strategy formerly developed to predict the daily maintenance dose of warfarin from the prothrombin time ratio or the thrombotest performed 3 days after starting the treatment may also be applied to fluindione and the INR measurement.

Bone mineral decrease in the leg with unilateral chronic occlusive arterial disease.

OBJECTIVE: The links between osteoporosis and arteriosclerosis have been established by numerous epidemiological studies. Could arteriosclerosis induce bone mineral loss via ischemia or other pathological process? We carried out a comparative study of bone mineral density in both legs of patients with unilateral arterial disease of the lower limbs. METHODS: We studied 25 patients, 22 men and 3 women, whose mean age was 62.3 years (range 35-88 years). These patients had unilateral lower limb arterial disease of at least 3 months duration with a systolic index at least 50% lower on the affected than on the healthy side. Bone mineral content (BMC) and bone mineral densities (BMD) of the femoral neck, femur, tibia, foot and ankle of the affected and the unaffected legs were measured by dual x-ray absorptiometry (Lunar DPXL) and the results compared. RESULTS: Bone mineral density was significantly lower in the femur (-3.7%, p = 0.04), the foot and the ankle (-3%, p = 0.05) of the affected leg. There was a non-significant decrease in BMD of the whole femoral neck (-1.2%) and the trochanter (-4.4%, p = 0.08) on the affected side. Tibial bone mineral density was identical in both legs. Bone mineral content was lower on the affected side (-5.3%, p = 0.05) whereas fat mass and muscle mass were the same in both legs. CONCLUSION: The ischemia resulting from arterial disease of the lower limbs appears to have a direct deleterious effect on bone mineralization.

Myocardial contractility: non-invasive assessment after cardiac surgery.

The shape of the carotid blood-flow signal in the assessment of myocardial contractility is important. The non-invasive electromagnetic method permits the measurement of the pulsatile carotid flow rate and thus to estimate the maximum blood flow acceleration (max. dF/dt), which is directly related to myocardial contractility. The electromagnetic flowmeter method, routinely used in the superficial arteries of arteriosclerotic patients, has been modified to record the blood flow rate in the carotid artery. Two ECG electrodes on both sides of the common carotid artery record the signal given by a small magnet located above the electrodes. Using this method, we have studied the effects of isoprenaline infusion in a normal subject. In patients after cardiac surgery we measured max. dF/dt in the region of the carotid artery and compared changes in it with parameters obtained by invasive methods such as the cardiac index, and the pulmonary and systemic pressures. The first results of blood flow recordings in the ascending aorta are presented here.

Intermittent claudication in older patients. Practical treatment guidelines.

The prevalence of intermittent claudication (IC) increases with age; when questioned, older patients consider increased difficulty in walking to be a normal consequence of aging. Although the prognosis for the involved limb with IC is relatively good, IC is an important clinical predictor of increased cardiovascular mortality. It is important to effect a minimal strategy for determining the presence of lesions in different vascular regions: carotids, coronaries, aorta and renal arteries. The goals for the treatment of IC in the elderly are to improve the walking distance and quality of life and to increase survival. Practical guidelines for the treatment of IC are to first establish a correct diagnosis. Then, patients have to apply life-style modifications and participate in an exercise programme, with the next treatment step involving the use of antiplatelet drugs. However, it must be remembered that older patients could have limitations on exercise; in such cases, a vasoactive drug should be considered. The third guideline consists of multifocal evaluation of the arteries, specifically the coronaries, carotids and abdominal aorta. The existence of an iliac obstruction or stenosis requires consideration of the 2 last guidelines. In more than 75% of cases, elderly patients have femoropopliteal or distal arterial obstructions: exercise and a vasoactive drug should be employed in these instances. The presence of iliac lesions has to be discussed in the presence of a multidisciplinary team in a vascular centre, and should consider the usefulness of percutaneous transluminal angioplasty or surgery.