[Clinical and ultrasonographic follow-up after femoro-popliteal venous bypass for lower limb revascularization]. / Surveillance clinique et échographique des pontages veineux fémoro-poplités des membres inférieurs.

Revascularisation of the lower limbs with vein graft is frequent. Femoro-popliteal infrainguinal bypass have good permeability rates at five years. The weak point of autogenous vein bypass grafting is vein graft stenosis, which develops particularly in the first post-operative year. Stenoses are mostly in relation with myo-intimal hyperplasia and are often located at anastomoses. Serial arteriography and echographic studies have shown that the development of intrinsic graft stenosis is found in 20 to 30% of vein conduits in the lower extremity. On the basis of an abundance of clinical data, Duplex ultrasound surveillance of infrainguinal vein graft to detect and repair such lesions before graft occlusion is widely accepted and has shown in many retrospective studies to have a positive influence on lifetime of venous grafts. Critical stenosis (peak systolic velocity (PSV) > 300 cm/s and velocity ration (VR) > 4) should undergo surgical revision as it heralds occlusion of the vein graft in short delays. Intermediate stenosis (peak systolic velocity (PSV) 200-300 cm/s and velocity ratio (VR) 2-4 should be accurately followed as 50 to 70% progress to critical stenosis. Use of echo-doppler monitoring is supported by one randomised study which showed superiority of ultrasound surveillance over clinical surveillance, and by a well described relation between graft thrombosis and an increased amputation rate. In contrast, Duplex ultrasound surveillance for prosthetic grafts is not widely accepted primarily because of the occurrence of rare intrinsic lesions in prosthetic grafts, compared to in vein grafts. Vascular doctors are increasingly concerned with the costs of surveillance program and of surgical interventions. Recent economic appraisal have shown that cost associated with graft maintenance is significant, particularly in the first-year and demands consideration. However revision of a duplex-identified stenosis seems to be less costly than revision after graft thrombosis. Costs of limb amputation and the following expense of postamputation rehabilitation are very high and justify limb-salvage-related expense. The results of an ongoing randomised controlled trial (the Vein Graft Trial) comparing duplex ultrasound surveillance against clinical surveillance only will certainly bring more data on the benefits of echographic surveillance.

High resolution unenhanced computed tomography in patients with swollen legs.

PURPOSE: To evaluate the accuracy of computed tomography (CT) scan imaging in distinguishing lymphedema from deep venous thrombosis (DVT) and lipodystrophy (lipedema) in patients with swollen legs. MATERIAL AND METHODS: CT scans of the lower limbs were performed in 55 patients with 76 swollen legs (44 lymphedemas, 12 DVT and 20 lipedemas). Thirty-four normal contralateral legs were also similarly evaluated. Primary lymphedema was verified by lymphography or lymphoscintigraphy, whereas secondary lymphedema was documented by a typical clinical history. DVT was established by ultrasound Doppler imaging. The diagnosis of lipedema was made with bilateral swollen legs where lymphoscintigraphy and Doppler examination were both unremarkable. Qualitative CT analysis was based on skin thickening, subcutaneous edema accumulation with a honeycombed pattern, and muscle compartment enlargement. RESULTS: Sensitivity and specificity of CT scan for the diagnosis of lymphedema was 93 and 100%, respectively; for lipedema it was 95 and 100%, respectively; andfor DVT it was 91 and 99%, respectively. Skin thickening was found in 42 lymphedemas (95%), in 9 DVT (75%), and in 2 lipedemas (16%). Subcutaneous edema accumulation was demonstrated in 42 legs (95%) with lymphedema and in 5 (42%) with DVT but in none with lipedema. A honeycombed pattern was present only in lymphedema (18 legs or 41%); muscle enlargement was present in all patients with DVT, in no patient with lipedema, and in 4 (9%) with lymphedema. CONCLUSION: Edema accumulation is readily demonstrated with plain CT scan and is not present in lipedema. Specific CT features of the subcutaneous fat and muscle compartments allow accurate differentiation between lymphedema and DVT.

[Genetics of lymphedema: from Milroy's disease to cancer investigations]. / La génétique du lymphoedème: de la maladie de Milroy aux applications en cancérologie.

New insight has recently been obtained into the molecular mechanisms regulating lymphatic development and function during embryogenesis. VEGF-C and D ligands have been shown to stimulate lymphangiogenesis and their lymphatic-specific receptor VEGFR-3 is linked to the human congenital and hereditary lymphedema in humans. Above all, new focus on lymphatic endothelial cells gives opportunities for developing innovative therapies for lymphedema and cancer metastasis.

[Physical therapy of lymphedema: Montpellier's experience]. / Physiothérapie des lymphoedèmes: l'expérience de Montpellier.

Authors have presented their experience for treatment of lymphedema during 5 consecutive days. After intensive phase of treatment at hospital, specific therapy is described to maintain results. Complex decongestive physiotherapy includes manual lymphatic drainage and bandage which are modified with original methods every day if necessary.

[Two cases of polyarteritis nodosa with a good prognosis?]. / Deux périartérites noueuses de bon pronostic?

INTRODUCTION: Polyarteritis nodosa is a systemic necrotizing vasculitis that may become serious, even with no usual poor prognosis factors. EXEGESIS: We report two cases of polyarteritis nodosa with negative histology, starting only with an extensive necrosis of the extremities. The treatment, associating corticosteroids and, secondarily, immunosuppressors, did not prevent a bilateral half-leg amputation for the two patients. In the first case the disease stabilized, but in the second one, it worsened, leading to death within 2 years. CONCLUSION: This clinical aspect of the disease is unusual and should be identified because of its bad prognosis. It might benefit from a treatment from the outset associating corticosteroids and immunosuppressors, even with no usual bad prognosis factors.

[Vascular complications of homocystinuria: a retrospective multicenter study]. / Les manifestations vasculaires de l'homocystinurie: étude rétrospective multicentrique.

PURPOSE: Arterial or venous thromboses are frequent in patients with homocystinuria. Because severe homocystinuria is rare, prevalence of thrombosis, especially in France, is still unknown. METHODS: Review of the clinical outcome of 37 patients with homocystinuria due to cystathionine-cystathionine beta-synthase deficiency (34) and 5,10-methylenetetrahydrofolate reductase (three) lead us to describe vascular complications occurring in 12 (32%) of them. RESULTS: Venous thromboembolism is the earlier and the most frequent one and is mainly found in untreated late-diagnosed cases. Under specific treatment of homocystinuria, thromboses are rare and always a complication of surgery associated with high thromboembolic risk. Association with factor V Leiden increased the risk of venous thrombosis.

[The paradox of hemostasis in the centenarian]. / Le paradoxe de l'hémostase du centenaire.

Vascular aging in humans is associated with heightened coagulation enzyme activity. This state of hypercoagulability is compatible with longevity and health. Mechanisms beyond this equilibrium associated with longevity are unknown and studies on polymorphims associated with vascular disease have not been helpful in understanding this phenomenon.

Lower limb vein enlargement and spontaneous blood flow echogenicity are normal sonographic findings during pregnancy.

PURPOSE: We studied pregnancy-induced changes in lower limb venous function. METHODS: We used plethysmography and sonography to assess the changes in venous wall distensibility, saphenous vein diameters, and spontaneous blood flow echogenicity in the common femoral veins in 190 consecutive women during and after uncomplicated pregnancies (total of 409 examinations). RESULTS: The percentage of women with clinical symptoms and signs of venous insufficiency increased significantly during pregnancy. The mean diameters of the great and small saphenous veins also increased significantly, while occlusive venous plethysmography showed a decrease in parameters indicating vein distensibility. Spontaneous blood flow echogenicity in the common femoral veins was clearly visible or marked in 6% of cases during the first trimester of pregnancy, 63% during the second trimester, and 96% during the third trimester, versus 6% after delivery (p < 0.0001). The mean hematocrit decreased and the mean fibrinogen concentration increased during pregnancy. CONCLUSIONS: The increase in lower limb venous pressure seen during pregnancy leads to venous overdistention and worsens blood stasis. Decreased venous flow velocity and rheological alterations result in increased red cell aggregation, giving rise to spontaneous blood flow echogenicity. Spontaneous blood flow echogenicity is therefore a normal finding during pregnancy and should not be mistaken for venous thrombosis.

[Manual lymphatic drainage]. / Drainage lymphatique manuel.

Manual physiotherapy of lymphoedema is the best treatment for chronic venous and lymphatic stasis of the lower limbs. It consists in handlings of the limb for the appeal and the resorption of the lymph but it cannot be used alone. It must be associated with other techniques: defibrosing, skin care, compressive bandages, muscular exercise. Contensive and compressive bandagings prolong the action of lymphatic drainage. The main indication of manual physiotherapy is primary or secondary lymphoedema but also chronic venous disease, and in some selected cases acute venous thrombosis and traumatic or post-traumatic pains.

[Teaching targets in vascular medicine]. / Objectifs pédagogiques en médecine vasculaire.

The reference list presented here is a selection of educative objectives performed by the French "Collège des Enseignants de Médecine Vasculaire" for the different levels of the medical initial education course. It was produced through a collective procedure, after selecting the most relevant topics and setting up writing rules based upon docimology, and favoring practical rather than theoretical objectives. The main topics are peripheral obstructive arterial disease, polyatherosclerosis, atherosclerosis risk factors, venous thromboembolic disease, thrombophilia, chronic venous insufficiency, lymphatic insufficiency, leg ulcers, vascular acrosyndromes, cerebrovascular diseases and connective tissue diseases, vascular occupational diseases, vascular adverse effects of drugs, diabetic vascular disease, the vascular consequences of hypertension, vascular malformations and angiodysplasia, inflammatory arterial diseases, and vascular explorations. As a whole they include about 300 objectives for the five teaching levels. We hope that this list will help stimulate production of training courses and documents strongly needed in this field.

A comparison of enoxaparin with placebo for the prevention of venous thromboembolism in acutely ill medical patients. Prophylaxis in Medical Patients with Enoxaparin Study Group.

BACKGROUND: The efficacy and safety of thromboprophylaxis in patients with acute medical illnesses who may be at risk for venous thromboembolism have not been determined in adequately designed trials. METHODS: In a double-blind study, we randomly assigned 1102 hospitalized patients older than 40 years to receive 40 mg of enoxaparin, 20 mg of enoxaparin, or placebo subcutaneously once daily for 6 to 14 days. Most patients were not in an intensive care unit. The primary outcome was venous thromboembolism between days 1 and 14, defined as deep-vein thrombosis detected by bilateral venography (or duplex ultrasonography) between days 6 and 14 (or earlier if clinically indicated) or documented pulmonary embolism. The duration of follow-up was three months. RESULTS: The primary outcome could be assessed in 866 patients. The incidence of venous thromboembolism was significantly lower in the group that received 40 mg of enoxaparin (5.5 percent [16 of 291 patients]) than in the group that received placebo (14.9 percent [43 of 288 patients]) (relative risk, 0.37; 97.6 percent confidence interval, 0.22 to 0.63; P< 0.001). The benefit observed with 40 mg of enoxaparin was maintained at three months. There was no significant difference in the incidence of venous thromboembolism between the group that received 20 mg of enoxaparin (43 of 287 patients [15.0 percent]) and the placebo group. The incidence of adverse effects did not differ significantly between the placebo group and either enoxaparin group. By day 110, 50 patients had died in the placebo group (13.9 percent), 51 had died in the 20-mg group (14.7 percent), and 41 had died in the 40-mg group (11.4 percent); the differences were not significant. CONCLUSIONS: Prophylactic treatment with 40 mg of enoxaparin subcutaneously per day safely and effectively reduces the risk of venous thromboembolism in patients with acute medical illnesses.

Spatial and temporal expression of the cystathionine beta-synthase gene during early human development.

We report the cystathionine-beta synthase (CBS) gene expression pattern during early human embryogenesis (3 to 6 weeks post conception) by in situ hybridization and in fetal and adult tissue by Northern Blot analysis. Probes were chosen to recognize either the common sequence to all known CBS mRNAs or the sequences of two different major exons 1 issued of we have previously identified. We demonstrate by in situ hybridization that CBS is continuously expressed from the earliest stages studied (22 days post conception) during embryogenesis in the tissues of developing embryos which will after birth present clinical abnormalities in homocystinuria patients. It is expressed at an especially high level in the neural and cardiac systems until the liver primordium appears. In embryonic central nervous system, the whole neural tube and primary brain vesicles are labeled. Secondary brain vesicles labeling are dependent on the neuroepithelium differentiation. The ventricular layer of the rhombencephalon, cranial nerve nuclei and then after cerebellar cortex derived from rhombencephalon ventricular layer are strongly labeled. Thalamus and other derivatives of the diencephalon plate, the neuroblastic layer of the retina, lens and dorsal root ganglia are labeled. After 35 days post conception, CBS mRNAs was detected in endocardial cells and in cells derived from the neural crest of the heart and in particular developing mesodermic regions such as the primitive hepatocytes of the liver, mesonephros vesicles, various endocrine glands and developing bones. We could not detect tissue specificity of different probes at this embryonic stage. Northern blot analysis consistently detected mRNA species in fetal 25 weeks post conception brain, liver and kidney. The common cDNA probe revealed the 2.5 and 3.7 kb mRNA species from brain, liver and kidney. The exon 1b probe detected only the 2.5 kb mRNA and the exon 1c probe the 3.7 kb mRNA in these three tissues. In adult tissue, the 1b probe detected only the 2.5 kb mRNA and the 1c probe only the 3.7 kb mRNA in the liver.

[Homocysteine, 5,10-methylenetetrahydrofolate reductase and deep venous thrombosis. Survey of 120 patients in internal medicine]. / Homocystéine, 5,10-méthylènetétrahydrofolate réductase et thrombose veineuse profonde. Enquête auprès de 120 patients en médecine interne.

BACKGROUND: In the last few years, the association of deep vein thrombosis with frequent biological risk factors and genetic polymorphisms has significantly modified the field of venous thrombosis. In this study, we measured plasma homocysteine levels and tested the C677T methylenetetrahydrofolate reductase (MTHFR) mutation. PATIENTS AND METHODS: Plasma homocysteine levels and test for C677T MTHFR mutation were performed in 120 consecutive patients with objectively diagnosed deep vein thrombosis, and in 120 controls. RESULTS: We found a strong association between hyperhomocysteinemia and thrombosis (odd ratio: 2.43 IC 95% [1.27-4.7]). Conversely the C677T MTHFR gene polymorphism is only associated with hyperhomocysteinemia but not associated with thrombosis. CONCLUSION: This is a preliminary study to the ongoing international multicentric study of SNFMI (Société nationale française de m0+edecine interne) concerning hyperhomocysteinemia and venous thrombosis.

A woman with five consecutive fetal deaths: case report and retrospective analysis of hyperhomocysteinemia prevalence in 100 consecutive women with recurrent miscarriages.

OBJECTIVE: To evaluate the medical relevance of hyperhomocysteinemia in women with primary recurrent miscarriages. DESIGN: Case report and retrospective cross-sectional study. SETTING: Hematology outpatient department of a university hospital. PATIENT(S): Case report concerning a woman with five consecutive fetal losses. One hundred consecutive women with primary recurrent unexplained miscarriages (study group) and matched healthy controls (control group) with no antecedent fetal loss. INTERVENTION(S): Venous blood sample collection in resting individuals. MAIN OUTCOME MEASURE(S): Plasma total homocysteine concentrations, plasma folate concentrations, and DNA analysis for the C677T mutation of the 5,10 methylene tetrahydrofolate reductase gene. Normal threshold homocysteine concentration was obtained from values found in the control group (95th percentile). RESULT(S): The case patient was hyperhomocysteinemic, was homozygous for the C677T mutation in the methylene tetrahydrofolate reductase gene, and had plasma folate deficiency. Folic acid and pyridoxine administration normalized the homocysteine concentration and favored a successful pregnancy. In the retrospective study, 12 of 100 patients were hyperhomocysteinemic. Twenty percent had the C677T methylene tetrahydrofolate reductase genotype and 15% had low plasma folate concentrations. The highest values of homocysteine concentration were found in patients with both the C677T genotype and folate deficiency. CONCLUSION(S): Hyperhomocysteinemia should be identified in women with recurrent miscarriages because therapeutic normalization might permit a normal birth.