[Therapeutic consequences of thrombophilic testing]. / Conséquences thérapeutiques de la mise en évidence d'une thrombophilie.

OBJECTIVE: The objectives of this article are to review the data about the consequences of thrombophilia testing and to think about its indications. CURRENT KNOWLEDGE AND KEY POINTS: The indications of congenital thrombophilic testing have extended since the discovery of prevalent abnormalities, such as mutations of factor V or II genes. However, thrombophilia does not result in a significant increase in the risk of recurrence unlike the spontaneous occurrence of thrombotic events. The factor V Leiden mutation is associated with a moderate increase in recurrence rate, while the G20210A mutation of factor II is not associated with a significant increase in recurrence. Regarding the decrease in natural anticoagulants is concerned, there is no definite conclusion, although the decrease in antithrombin is suspected of being associated with an increase in recurrence. FUTURE PROSPECTS AND PROJECTS: Finally, identification of a constitutional thrombophilia most often do not influence the therapeutic decisions unless some rare abnormalities are found, such as a decrease in antithrombin, homozygous mutations in factors V or II genes or associations of thrombophilia. One must remember that antiphospholipid antibodies must be searched because their impact on recurrences is well-known. Diagnostic work-up for thrombophilia is not useful after a distal or a superficial venous thrombosis (except for antiphospholipid antibodies in case of distal venous thrombosis).

[Psychiatric adverse effects of fluoroquinolone: review of cases from the French pharmacologic surveillance database]. / Effets indésirables psychiatriques des fluoroquinolones: cas notifiés à la pharmacovigilance française.

INTRODUCTION: Psychiatric adverse effects of fluoroquinolones are known for long, but can sometimes be missed. We analyse cases spontaneously reported to the French pharmacovigilance. METHODS: Cases of psychiatric adverse effects with fluoroquinolones reported to the French pharmacovigilance system were analysed. The studied period was from January 1985 and June 2002. Data analysed included age, sex, adverse effect, fluoroquinolone, seriousness and evolution. RESULTS: Five hundred ninety cases have been reported concerning 273 males and 316 females (sex unknown in 1 case). Mean age was 66 years (median: 70, range: 12-102). The most frequently reported psychiatric adverse effects were confusion (51%), hallucinations (27%), agitation (13%), delusion (12%), insomnia (8%), somnolence (4%) (several adverse effects could be associated in a single patient). Serious cases represented 21.7% (resulting in hospitalisation in most cases). Evolution was favourable in most cases (88.5%), and was unknown in 9.5% of cases. CONCLUSION: The number of cases reported during this period is moderate, but under-reporting probably interferes. The eventuality of this kind of adverse effect with fluoroquinolones should be kept in mind. Dose should be adjusted to renal function, especially in older patients.

[Subacute ischemia of the lower limb revealing hyperhomocysteinemia in a young woman]. / Ischémie subaiguë d'un membre inférieur révélant une hyperhomocystéinémie chez une femme jeune.

A 51-year-old woman had no known cardiovascular risk factor. She presented with bilateral calf intermittent claudication from February. She was hospitalized in August for acute right leg ischemia without loss of sensorymotor functions, following angiography by one week. She had an occlusion of both superficial femoral arteries and abdominal aorta thrombus, plausible source for embolism. Her condition quickly improved with heparin and iloprost infusion. Since the aortic thrombus was removed on ultrasound, aortic surgery was not performed at this time. Investigations showed hyperhomocysteinemia (25 microg/L after overnight fasting and 115 after methionin load) and decrease in folic acid. This report highlights the occurrence of severe arterial disease in young women with high serum homocysteine levels.

[Painful bruising syndrome: a psychogenic disease]. / Syndrome des ecchymoses douloureuses: une maladie psychogène.

INTRODUCTION: Painful bruising syndrome was described by Gardner and Diamond in 1955. It is marked by spontaneous bruising, without any biological abnormality, affecting young women with pathological mental context. EXEGESIS: We report three observations with painful bruising syndrome. In a patient, psychotherapy induced improvement in dermatological and articular manifestations. In other case, placebotherapy made clinical symptoms go away for a prolonged period. CONCLUSION: Some etiological hypotheses have been postulated for Gardner and Diamond syndrome. However, published cases speak in favour of psychogenic hypothesis. Somatic and psychological approach must be offered to these patients.

The enzymatic antioxidant system in blood and glutathione status in human immunodeficiency virus (HIV)-infected patients: effects of supplementation with selenium or beta-carotene.

To investigate the effects of selenium or beta-carotene supplementation in human immunodeficiency virus (HIV)-infected patients, who are known to have deficiencies of selenium and vitamin A, we evaluated the blood enzymatic antioxidant system, including superoxide dismutase (SOD), selenodependent glutathione peroxidase (GPX), and catalase (Cat); glutathione (GSH) status; and plasma selenium concentration. The placebo group consisted of 18 HIV-infected patients with no supplementation, the selenium group was composed of 14 patients receiving oral selenium treatment, and the beta-carotene group comprised 13 patients receiving oral beta-carotene supplementation. All groups were studied for 1 y. At the beginning of the study, a significantly higher SOD activity (P < 0.001) was observed in all HIV-infected patients compared with uninfected control subjects, and GPX activity at baseline was higher in the placebo (P < 0.004) and selenium (P < 0.014) groups than in the control subjects. These higher enzyme activities could be related to an increased synthesis of these enzymes in erythrocyte precursors under oxidative stress. Moreover, we observed significantly lower GSH values in all HIV-infected patients than in control subjects at the beginning of the study (P < 0.001). After selenium or beta-carotene supplementation, no significant difference was observed for SOD activity compared with baseline. On the contrary, GPX activity increased significantly after selenium treatment (P < 0.04 between 3 and 6 mo), whereas a slight increase was found after beta-carotene treatment. Similarly, a significant increase in GSH values was observed at 12 mo compared with baseline both after selenium supplementation (P < 0.001) and beta-carotene supplementation (P < 0.01). Because GPX and GSH play an important role in the natural enzymatic defense system in detoxifying hydrogen peroxide in water, selenium supplementation could be of great interest in protecting cells against oxidative stress. The lower efficiency of beta-carotene could be attributed to the seriousness of the pathology at the time of recruitment into the beta-carotene group.

Endothelial dysfunction during acute methionine load in hyperhomocysteinaemic patients.

Hyperhomocysteinaemia has been associated with arterial and venous thrombosis possibly by causing damage to the endothelium. We hypothesised that an oral load in methionine, that increases plasma homocysteine, would also result in an increase in biological markers of endothelial or platelet dysfunction. Then we investigated two groups of patients with arterial or venous occlusive disease: 17 with hyperhomocysteinemia and 12 without hyperhomocysteinemia. We measured in both groups plasma soluble thrombomodulin, von Willebrand factor, P-selectin and tissue factor plasma inhibitor before and 6 hours after a load with 100 mg/kg oral methionine. Methionine load resulted in a significant increase in von Willebrand factor in both groups (P<0.02), suggesting that endothelial dysfunction occurs during the load.

Effect of the antioxidants selenium and beta-carotene on HIV-related endothelium dysfunction.

Patients infected with HIV are at increased risk of atherosclerosis, and have evidence of endothelium dysfunction. The hypothesis was tested that HIV-related endothelium dysfunction is related to loss of antioxidants. This was done by the supplementation of the antioxidants selenium and beta-carotene. We supplemented the diet of 10 HIV-seropositive subjects with 100 microg selenium daily, 11 subjects with 30 mg beta-carotene twice daily while 15 subjects were not supplemented. Plasma was obtained at outset and after a year, and tested by ELISA for endothelial cell, platelet and inflammatory markers. The non-supplemented patients experienced increases in von Willebrand factor and soluble thrombomodulin (both p <0.01). There were no changes in any of the indices in the patients taking selenium or beta-carotene. Increased von Willebrand factor and soluble thrombomodulin in the non-supplemented patients imply increased damage to the endothelium over the year of the study. Therefore we interpret the lack of increase in the patients taking antioxidants as evidence of the protection of the endothelium by these agents.

Soluble adhesion molecules and endothelial cell damage in HIV infected patients.

Endothelial damage is present in HIV infection but our understanding of markers and mechanisms is incomplete. We found increased levels of markers of endothelial cell damage such as von Willebrand factor (vWf), soluble thrombomodulin (sTM) and adhesion molecule E-selectin in 90 subjects seropositive for HIV relative to healthy controls. sTM was strongly raised in those patients with the lowest CD4+ cell count (p < 0.001), but levels of vWf increased at each incremental fall in CD4+ cell count and the two indices correlated significantly (r = -0.485, p < 0.001). vWf correlated strongly with levels of the inflammatory cytokines tumor necrosis factor (TNF-alpha) and alpha interferon (IFN-alpha) but sTM correlated only weakly with IFN-alpha. We suggest that increased vWf is largely the result of inflammatory stimulus of the endothelium but that sTM is found only in those patients with more severe disease, and so truly represents endothelial damage.

Clinical prediction of lower limb deep vein thrombosis in symptomatic hospitalized patients.

We evaluated two clinical scores for the prediction of deep venous thrombosis (DVT) in hospitalized patients (Wells' and Kahn's). We included 273 patients referred to the vascular exploration unit for the suspicion of DVT. A clinical questionnaire was tilled in by the practitioner and the scores were calculated from this form. 66 of the 273 patients had a DVT. When Wells' score was 3, a DVT was found by duplex echography in 51% patients; when the score was 0, a DVT was found in 9%. Kahn's score was not adapted to this population. We then developed a new simple score (cancer, palsy or plaster immobilization, warmth, superficial venous dilation, unilateral pitting edema, other diagnosis). A DVT was found in 76% patients with a score of 3 and in 11% in those with a score of 0. We therefore propose a 6-item score whose main advantages are simplicity and usefulness in routine practice.

Plasma vascular endothelial growth factor and its receptor Flt-1 in patients with hyperlipidemia and atherosclerosis and the effects of fluvastatin or fenofibrate.

Increased vascular endothelial cell growth factor (VEGF) may be important in cardiovascular pathophysiology (perhaps relating to angiogenesis and collateral vessel development) and binds target endothelium via receptors such as Flt-1. We hypothesized that there would be increased levels of plasma VEGF and Flt-1 in patients with atherosclerosis and others with hyperlipidemia compared with controls, and a reduction in these factors with 3 months of lipid-lowering therapy. Twenty patients with uncomplicated hyperlipidemia but no atherosclerosis, 20 patients with hyperlipidemia plus clear atherosclerosis, and 40 matched controls were studied. Plasma VEGF was higher in patient groups than in healthy controls (p <0.01), but Flt-1 was not significantly altered. After lipid-lowering therapy, patients with uncomplicated hyperlipidemia had significantly reduced total cholesterol and VEGF (all p <0.05) but no significant change in Flt-1. Lack of a significant correlation between the von Willebrand factor and VEGF suggests the latter is unrelated to endothelial damage. Plasma VEGF that increases in patients with uncomplicated hyperlipidemia free of major underlying atherosclerosis and in patients with hyperlipidemia plus established atherosclerosis is reduced by successful lipid-lowering treatment. These findings may have implications for the pathophysiology and treatment of hyperlipidemia and atherosclerosis, and suggest an alternative mechanism (i.e., modulation of angiogenesis) by which lipid-lowering therapy may reduce cardiovascular events beyond lipid reduction alone.

Antioxidant status (selenium, vitamins A and E) and aging.

Antioxidant status can be evaluated by blood selenium, vitamins A and E. The level of selenium was determined in whole blood, erythrocytes and plasma of 170 French people (70-95 years old) healthy and with intercurrent illness, by using PIXE (proton-induced X-ray emission analysis). These results are discussed with other values from the literature. Plasma levels of vitamins A and E have been measured by HPLC. All data were compared with those obtained for younger subjects. Healthy elderly people residing in a geriatric home received selenium supplements during 1 month. The influence of this supplementation brought to light a deficiency for this trace element. The correlation of aging and nutritional requirements with immune function, heart and cancer death rate is presented and discussed.

Spontaneous pneumothorax associated with Pneumocystis carinii pneumonia. Successful treatment with talc pleurodesis.

Spontaneous pneumothoraces occur in patients with acquired immunodeficiency syndrome and Pneumocystis carinii pneumonia. However, treatment with tube insertion and tetracycline sclerosis often fails to prevent recurrence. We present a single case of such a patient successfully treated with talc sclerosis.

Levels of plasma thrombomodulin are increased in atheromatous arterial disease.

The plasma thrombomodulin (TM) level depends on the integrity of the endothelium and the clearance of the molecule. In several different pathological conditions, plasma TM levels increase with damage to the endothelium. We studied plasma TM levels in patients with various localizations of atheromatous arterial disease who had normal serum creatinine levels. Two groups of patients had a single symptomatic localization, which was either peripheral occlusive arterial disease (POAD) or ischemic heart disease (IHD) and a third group of patients had multiple symptomatic localizations (polyvascular). We compared the plasma TM levels with the plasma levels of other specific markers of endothelial cell activation such as: prostacyclin (PGI2), tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1). Plasma TM levels were significantly increased in all three individual groups and when all patients were considered (total patients), as compared with normal controls. When all patients were considered, there was a significant positive correlation between plasma TM levels and t-PA and between plasma TM levels and PGI2. A significant positive correlation was also found between the plasma TM levels and PAI-1 for patients with POAD. Thus, our findings suggest that an increased influx of TM into the plasma may be caused by endothelial cell damage in patients with atheromatous arterial disease. However in our study, the plasma TM levels obtained were similar for all three types of atheromatous arterial disease. Though plasma thrombomodulin is a marker of endothelial cell injury, it cannot be of a clinical interest until its levels are related to the extend of the atheromatous lesions.(ABSTRACT TRUNCATED AT 250 WORDS)

Lipoprotein(a) in 505 hospitalized patients with various pathological states: correlations with cardiovascular diseases and therapies.

OBJECTIVE: Our aim was to study the lipoprotein (a) (Lp(a)) levels in various pathological states. EXPERIMENTAL DESIGN: This investigation was prospective and included a healthy control group. SETTING: This study was carried out in two internal medicine and angiology services in teaching hospitals. PATIENTS: 505 patients were included with various diseases: 66 acute infections, 9 HIV infections, 25 cancers, 86 diabetes, 36 systemic diseases, 94 atheromatous vascular disease, 27 arterial hypertensions. A control group was composed of 21 healthy subjects. INTERVENTIONS: There was no therapeutic intervention but cardiovascular treatments were recorded. MEASURES: Serum Lp(a), total cholesterol, triglycerides, HDL-cholesterol, calculated LDL-cholesterol, apolipoproteins A-I and B were measured together with inflammatory parameters, serum creatinine, proteinuria, serum aminotransferase activity. RESULTS: There was no difference in Lp(a) levels between controls and each patient group. However, a correlation was found in systemic diseases between Lp(a) and C reactive protein (r = 0.371, p = 0.026) or serum albumin concentration (r = 0.453, p = 0.006). In hypertension, Lp(a) correlated with serum creatinine (r = 0.420, p = 0.03). In the whole patient population, Lp(a) was correlated with cholesterol (r = 0.156, p = 0.0001), apolipoprotein B (r = 0.215, p = 0.0001), age (r = 0.108, p = 0.015), arterial events (r = 0.174, p = 0.0001) and platelet anti-aggregant drugs (r = 0.169, p = 0.0001). CONCLUSIONS: Lp(a), was related to atheromatous events and in systemic diseases to inflammation, suggesting that Lp(a) might vary in some patients in a manner similar to acute phase proteins.

Plasma thrombomodulin: new approach of endothelium damage.

Endothelium damage is associated with thrombotic risk in a variety of diseases including atherosclerosis, gram negative sepsis, viral infections and neoplastic disease. Therefore, it appears necessary to find a mean for the clinical investigation for such a damage. Among the markers of these cells, thrombomodulin which is a membrane glycoprotein, seems to be of great interest for this purpose. Actually, thrombomodulin is also found in plasma, following an endothelial lesion. Plasma levels of thrombomodulin are increased in a certain number of pathologies associated with endothelium lesion: atheromatous arterial disease, disseminated intravascular coagulation syndrome and also in systemic lupus erythematosus where the levels of plasma thrombomodulin are related to the severity of the pathology. Moreover, previous in vitro studies confirm the fact that the release of thrombomodulin from the endothelial cell membrane occurs during the course of injury by activated leukocytes or hydrogen peroxide. So, one can suppose a prospective interest in the measurement of plasma thrombomodulin as a diagnostic tool for the approach of endothelium damage.

Common carotid intima-media thickness: does it matter how it is measured.

AIM: Intima media thickness (IMT) has proved to be a useful tool in predicting cardiovascular morbidity. However, methods are not well standardized, and several software packages softwares are available although they have never been compared with one other. Thus, the extrapolation of data from large studies might be questionable on routine practice. Our objective was to compare 2 software packages largely used for semi-automatic measurement of IMT. METHODS: We have measured IMT on left and right common carotid in 97 patients in standardized conditions. RESULTS: The same image was processed through the 2 software (Metris and Iôdp). There was no difference for IMT measured at various times by the same investigator, although the number of measurable points increased as the operator became more experienced. The number of measurable points was significantly greater with Iôdp. IMT was lower with Iôdp than Metris (mean difference 0.066 mm on the right side). CONCLUSION: These results suggest that the same software must be used for repeated measurements in 1 patient. One must be careful in using data from large studies or normality values. At the individual level, the use of IMT to determine vascular risk is dependent upon the software used. It is urgent to standardize the methods of IMT measurement.

Cannabis arteritis revisited--ten new case reports.

The purpose of this paper was to revisit the old concept of cannabis arteritis first described in the 1960s and report 10 new cases. Ten male patients, with a median age of 23.7 years developed subacute distal ischemia of lower or upper limbs, leading to necrosis in the toes and/or fingers and sometimes to distal limb gangrene. Two of the patients also presented with venous thrombosis and three patients were suffering from a recent Raynaud's phenomenon. Biological test results did not show evidence of the classical vascular risk factors for thrombosis. Arteriographic evaluation in all cases revealed distal abnormalities in the arteries of feet, legs, forearms, and hands resembling those of Buerger's disease. A collateral circulation sometimes with opacification of the vasa nervorum was noted. In some cases, arterial proximal atherosclerotic lesions and venous thrombosis were observed. All patients were moderate tobacco smokers and regular cannabis users. Despite treatment with ilomedine and heparin in all cases, five amputations were necessary in four patients. The vasoconstrictor effect of cannabis on the vascular system has been known for a long time. It has been shown that delta-8- and delta-9-tetrahydrocanabinols may induce peripheral vasoconstrictor activity. Cannabis arteritis resembles Buerger's disease, but patients were moderate tobacco smokers and regular cannabis users. These cases show that prolonged use of cannabis could be an additive risk factor for juvenile and young adult arteritis. Cannabis arteritis is a forgotten and severe occlusive vascular disease occurring in young adults. Search for cannabis use may be an important tool for a better knowledge of arteritis in young smokers.

[Cutaneous circulation in sportsmen. A laser Doppler study]. / Circulation cutanée chez le sportif. Etude par Doppler laser.

The cutaneous blood flow serves a dual purpose: it feeds the skin but also, and chiefly, regulates body temperature. In this study variations in the skin blood flow of athletes were compared with those observed in non-athletes. We studied 18 non-athletes and 18 high-level athletes. Skin blood flow was measured before and after an exercise test, using a computerized laser Doppler system (PF3 periflux). After a physical exercise, athletes showed a significant increase of skin blood flow in areas of muscular activity, whereas this increase was half as much in non-athletes. Conversely, in areas other than those of muscular activity skin blood flow was reduced by 30% in athletes and increased by 100% in non-athletes. Intensive physical training therefore seems to generate a microcirculatory skin balance.

[The fate of patients with stenosis of the trunk of the left coronary artery]. / Devenir des sténoses du tronc de la coronaire gauche.

We have studied the fate of 49 patients with stenosis of the trunk of the left coronary artery of more than 50%. The follow-up period extends from 1,5 years to 5 years (with a mean of 33.83 +/- 13.55 months). The clinical picture was not characteristic. Unstable angina was found in 59% of cases. The exercice test (29 patients) was positive in 100%, with a mean depression of 3.3 mm. Stenosis of the trunk, which is rarely an isolated condition (8% of cases), is usually associated with disorders of the other main coronary vessels. Twenty six patients underwent surgery. Thirteen patients who were operable were treated medically. The performance of the left ventricle and the degree of involvement of the coronary arteries were comparable in these two groups. Seven inoperable patients were treated medically. Actuarial survival curves show a significant difference (p less than 0.01) in survival after two years between the operated cases (88%), the operable cases treated medically (60%), and the inoperable cases (57%). The decreased mortality of the operated cases corresponds also with a greater functional capacity in the survivors compared with that of the cases treated medically.

[Change in heart function in Duchênne de Boulogne myopathies at the severe progressive stage]. / Altération de la fonction cardiaque dans les myopathies de Duchênne de Boulogne au stade évolutif sévère.

Left ventricular function was studied in 15 patients with rapidly progressive Duchenne de Boulogne muscular dystrophy. Only one patient had a previous history of cardiac failure. All patients had typical electrocardiographical changes. Haemodynamic and angiographic investigation was performed in all patients. Three groups of patients were distinguished according to angiographic criteria : group I comprising 7 normal patients. group II comprising 4 "intermediary" patients, and group III of 4 patients with hypokinetic cardiomyopathy. Segmental ventricular dyskinesis was observed in 6 patients. Mitral incompetence was present in 2 cases and mitral valve prolpse in 1 case. All patients had a normal resting cardiac index. Patients in group II and III had end diastolic left ventricular pressures greater than 15 mmHg. An intravenous angiotensin test was performed in 4 patients from groups I and II. Impaired left ventricular function was demonstrated in patients thought to be normal in the basal state. Finally, myocardial involvement in this group of patients runs a parallel course to the duration and severity of the peripheral muscular disease.