[Prevention of chronic venous disease: which advice for our patients?]. / Prévention de la maladie veineuse chronique: quels conseils donner à nos patients?

Chronic venous disease (CVD) is a major public health problem due to its high prevalence and socioeconomic costs. In absence of adequate care, it can lead to chronic venous insufficiency (CVI). Disturbed venous-flow patterns lead to venous hypertension. Therefore, prevention of CVD involves venous hypertension reduction. In primary prevention, it is essential to inform the patient about necessary lifestyle changes. In case of CVD, it is essential to propose treatment (compression, venoactive drugs, and interventional treatments) to avoid CVI appearance and eventually offer the best therapy solutions for CVI complications.

[Superficial vein thrombosis: what's new in the management?]. / Thrombose veineuse superficielle: quelles nouveautés dans la prise en charge?

Lower limbs superficial venous thrombosis (SVT) is a relatively frequent disease. Its prevalence among patients consulting their treating physician is estimated to be 10.8% among women and 4.9% among men. Up to 25% of at risk patients with isolated SVT present with a concomitant DVT. Ultrasound imaging may play a role in the management of these patients allowing precise diagnosis, determination of thrombus extension and presence of associated DVT. From data recently appeared in the literature treatment of SVT with prophylactic doses of fondaparinux may be proposed to at risk patients with isolated SVT.

The paradoxical association between inherited factor VII deficiency and venous thrombosis.

Inherited factor VII (FVII) deficiency is considered to be a haemorrhagic disease. Nonetheless, some patients paradoxically present with venous thrombosis. We assessed whether there was a link between phenotype and genotype in seven patients with inherited FVII deficiency and thrombosis (eleven venous thrombotic events). For each patient (FVII:C < 50%), clinical data were collected, aetiological assessment of risk factors for thrombosis was investigated, and direct sequencing of the nine exons and promoter of the FVII gene (F7) was performed. We present the second series ever published on FVII patients with thrombosis. In nine of the eleven thrombotic events, there was at least one classical triggering risk factor; clinical (n = 4), familial antecedent (n = 2), or biological, defined by phospholipid-binding antibodies or elevated FVIII:C levels (n = 7). In contrast to a previous series, only two events occurred after surgery, performed both with and without replacement therapy. The thrombotic event remained unexplained in one young patient, highlighting the lack of 'protection' against venous thrombosis by low FVII:C levels. Genetic mutations were found to be heterogeneous. Among the seven F7 sequence alterations identified in the present study, only two (p.Ala354Val and p.Arg364Gln) have previously been reported in FVII-deficient patients presenting with venous thrombosis. Our genetic analyses of the F7 mutations in these patients show the complexity of FVII deficiency associated with thrombosis. These data justify a holistic, clinical and biological approach for patients with these specific symptoms. This series also strongly suggest that mild FVII deficiency should not prevent physicians from using antithrombotic prophylaxis in FVII-deficient patients.

Serial measurements of antineutrophil cytoplasmic autoantibodies in patients with systemic vasculitis.

PURPOSE: To assess the value of serial determinations of antineutrophil cytoplasmic autoantibodies (ANCA) for monitoring disease activity in patients with systemic vasculitis. PATIENTS AND METHODS: Forty-three patients with histologically proven vasculitis (21 with Wegener's granulomatosis, 17 with microscopic polyangiitis, and 5 with renal-limited vasculitis) were studied for a median follow-up of 22 months. Disease activity was prospectively assessed and quantified by the Birmingham Vasculitis Activity Score. A total of 347 sera were analyzed for ANCA determination. RESULTS: Relapses occurred in 23 (54%) of 43 patients. Diagnostic category (Wegener's granulomatosis vs micropolyangiitis and renal-limited vasculitis), severity of initial symptoms (mean vasculitis activity score, mean number of organs involved), and ANCA pattern [cytoplasmic-ANCA (c-ANCA) vs perinuclear-ANCA (p-ANCA)] did not significantly differ between relapsers and nonrelapsers. Lung involvement was more frequent at onset among relapsers [16 of 23 (70%) vs 6 of 20 (30%); P = 0.02]. Relapses were slightly, but not significantly, more frequent in patients with Wegener's granulomatosis or a c-ANCA pattern. The percentage of relapsers was greater in patients with persistently positive ANCA than in patients with negative or decreasing ANCA titers (86% vs 20%, P = 0.0001). However, the predictive value of an increase in ANCA titers for the occurrence of a subsequent relapse was only 28% (4 of 14) for c-ANCA, 12% (2 of 17) for anti-proteinase 3-ANCA, and 43% (6 of 14) for anti-myeloperoxidase-ANCA. An increase in ANCA occurred before or during relapse in 33% (10 of 30) of cases for c-ANCA/anti-proteinase 3 antibodies, and 73% (11 of 15) of cases for anti-myeloperoxidase antibodies. CONCLUSION: The persistence of ANCA positivity is strongly associated with relapses. However, an increase in ANCA titers has a poor value for the early prediction of a subsequent relapse and should not be used as a sole parameter for therapeutic intervention. In addition, our results suggest that serial anti-myeloperoxidase determination may be useful as a prognostic marker in patients who are p-ANCA positive.

Insulin sensitivity, insulin action, and fibrinolysis activity in nondiabetic and diabetic obese subjects.

Because inconsistencies occur with regard to the relative contribution of insulin to the hypofibrinolysis characteristic of obesity and diabetes, we explored the relationship between insulin and fibrinolysis, assessing both insulin sensitivity and insulin action. Seventeen markedly obese subjects (body mass index [BMI], 34.0+/-1.6 kg/m2; 12 nondiabetic and five diabetic) were studied using the three-step euglycemic-hyperinsulinemic clamp technique. Since the circadian rhythm of the fibrinolytic system may obscure a true effect of insulin, variations in fibrinolysis parameters observed during the glucose clamp were compared with those occurring spontaneously because of the circadian rhythm. Compared with six normal-weight subjects (BMI, 21.0+/-0.9 kg/m2), all obese subjects exhibited basal hyperinsulinism (fasting plasma insulin, 16.0+/-1.4 v 9.8+/-1.3 microU/microL, P < .001; fasting plasma C-peptide, 1.4+/-0.2 v 0.5+/-0.2 ng/mL, P < .001), hypofibrinolysis (euglobulin lysis time [ELT], 378+/-29 v 222+/-31 minutes, P=.01; tissue plasminogen activator [tPA] antigen, 7.8+/-0.9 v 4.2+/-0.5 ng/mL, P=.04; plasminogen activator inhibitor type 1 [PAI-1] activity, 22.2+/-2.5 v3.9+/-0.6 AU/mL, P=.004), and marked insulin resistance (M value, ie, the maximal glucose disposal rate, 9.1+/-0.6 v 18.6+/-0.8 mg/(kg x min), P < .001). The M value correlated inversely with tPA antigen (r=-.46, P=.05). During insulin infusion, values for fibrinolysis parameters decreased, but were not different compared with variations due to the circadian rhythm. In conclusion, our findings together with previously reported data reinforce the idea that chronic hyperinsulinism is linked to hypofibrinolysis, but insulin does not seem to acutely regulate the fibrinolysis system.

Angiosarcoma variant of Kasabach-Merritt syndrome.

Kasabach-Merritt syndrome is characterized by the occurrence of disseminated intravascular coagulation (DIC) usually caused by benign angiomatous tumours. Here we report the case of a 70-year-old man in whom DIC revealed a locally advanced hepatic tumour. Although DIC resolved with heparin, antithrombin III, fresh frozen plasma and corticosteroids, the patient died from haemoperitoneum following a fall, 3 months after the initial observation. Histopathological examination by autopsy allowed the diagnosis of hepatic angiosarcoma. The physiopathogenic mechanisms and treatment options are discussed.

Liver granulomatosis is not an exceptional cause of hypercalcemia with hypoparathyroidism in dialysis patients.

In 4 of our patients on chronic dialysis, we were intrigued by the association of hypercalcemia +/- hyperphosphatemia and normal intact PTH, with anicteric cholestasis without cytolysis. This picture occurred in 2 patients after they resumed dialysis because of a transplant rejection and in a third one after discontinuation of corticosteroids, prescribed for an idiopathic thrombocytopenia. No patient was under calcitriol, CaCO3 therapy, and their hypercalcemia persisted on a low calcium dialyzate (1.25 mmol/l). Obvious etiologies of hypercalcemia were not found: vitamin D or A intoxication, hyperparathyroidism, aluminum intoxication, hemopathy, HIV infection. The hypothesis of a granulomatous disease was made and a liver biopsy was performed showing granulomas with giant epitheloid cells. In one case foreign material (silicon ?) was present in the macrophages. Extensive investigations for sarcoidosis, tuberculosis and mycosis were negative. In 2 cases the so-called "dialysis" granulomatosis actually occurred in transplanted patients, suggesting the role of a transplantation related factor (toxic or virus). In the last case HCV seroconversion was present. In the 4 cases, corticotherapy led to the disappearance of hypercalcemia and to an increase of PTH. Our patients had the biological pattern of low bone turnover disease (hypercalcemia and normal intact PTH) and bone biopsy performed in 2 showed osteomalacia or ABD without aluminum. The association of this pattern with cholestasis should evoke liver granulomatosis, which should be confirmed by a liver biopsy and lead to a treatment by corticosteroids. The masking effect of previous corticoid therapy for transplantation should be pointed out. In 2 cases serial monitoring of plasma calcitriol showed a relation between decreasing high normal calcitriol with prednisone and normalization of calcemia, suggesting the role of inappropriate synthesis of calcitriol by the granuloma. In conclusion, liver granulomatosis should be looked for in dialysis patients on the association of unexplained hypercalcemia and normal PTH with anicteric cholestasis, and confirmed by a liver biopsy. Although still of unknown etiology, its evolution is favourable under corticotherapy.

[Transesophageal echographic demonstration of ulcerated atheromatous plaques of the thoracic aorta responsible for cholesterol emboli]. / Mise en évidence par échographie transoesophagienne de plaques athéromateuses ulcérées de l'aorte thoracique à l'origine d'embolies de cholestérol.

The authors present of case of a 61-year-old man suffering from cholesterol emboli, in whom transoesophageal echocardiography revealed complex atheromatous lesions of the thoracic aorta. There is growing emphasis, at the present time, on the concept of triggering factors with the multiplication of endovascular radiological investigations, the more widespread availability of cardiac surgery and the use of anticoagulants and fibrinolytics. The prognosis is poor, treatment is only palliative and preventive measures are therefore essential.

[Non-bacterial thrombosing endocarditis. Apropos of 2 cases]. / Endocardite thrombosante non bactérienne. A propos de deux cas.

The diagnosis of nonbacterial thrombosing endocarditis or marasmic endocarditis must be considered in patients presenting with a combination of cancer and systemic embolism. The pathophysiological mechanisms of this entity are unclear and purely hypothetical. However, hypercoagulability appears to play an essential role in the pathogenesis of this endocarditis, which could be the cardiac expression of a coagulopathy involving the entire vascular system. The authors report two cases of marasmic endocarditis which emphasize the value of transthoracic and transoesophageal echocardiography in the difficult diagnosis of this disease.

[Mixed cryoglobulinemia]. / Les cryoglobulinémies mixtes.

Mixed cryoglobulinemia are divided in two types: type II is the association of polyclonal IgG and a monoclonal IgM and type III is the association of polyclonal IgG and polyclonal IgM. In 70 p. 100 of cryoglobulinemia, a cause may be found (hematologic, auto immune disorder, infections, hepatic disorders), in some cases the recognition of the cause is delayed. In 30 p. 100 of cases, no cause can be identified and the cryoglobulinemia is considered as essential. Main clinical finding are purpuric skin rash, urticaria, arthralgia, motor sensitive polyneuropathy, diffuse proliferative glomerulo nephritis. Biological signs associate anemia, rheumatoïd factor and hypocomplementemia. Mixed essential cryoglobulinemia (the Meltzer and Franklin syndrome) is characterized by a systemic vasculitis involving small and middle size vessels.

[Physiology and pharmacology of lacrymal and salivary secretions]. / Physiologie et pharmacologie des sécrétions lacrymale et salivaire.

Salivary and lacrymal glands have secretory mechanisms similar to those of other exocrine glands. Saliva results from two different but integrated processes i.e. hydroelectrolytic transport and protein secretion by regulated exocytosis. Both cellular processes are regulated by the autonomic nervous system with complementary effects without antagonism, and parasympathetic innervation predominates. Signal transduction mechanisms in salivary cells include: increases in cytosolic calcium, cyclic AMP and cyclic GMP. The tear film consists of three layers: mucous inner layer, middle aqueous layer, and outer lipid layer. Each layer secretion is strongly regulated. Aqueous layer secretion is controlled by autonomic nervous system and signal transduction depends from cyclic AMP and intracellular calcium levels. A review of drugs used in France modulating lacrymal and salivary secretions is proposed.

[Thrombotic thrombocytopenic purpura and hemolytic-uremic syndrome in adults. Apropos of 27 cases]. / Purpura thrombotique thrombocytopénique et syndrome hémolytique et urémique de l'adulte. A propos de 27 observations.

UNLABELLED: We report a series of 27 patients included on the basis of either thrombotic microangiopathy (TMA) at renal histology (13 cases) or, in the absence of histology, non-immunological hemolytic anemia with schizocytes and thrombopenia (14 cas). The etiopathogenic treatment consisted in the administration of antiagregating agents (in all patients except 3 of group I because of the severity of thrombopenic), corticosteroids (1 case), intravenous immunoglobulins (2 cases) fresh frozen plasma (FFP) without plasma exchange (PE) in 7 cases and PE with FFP in 13 patients. According to the 6 months outcome, 4 groups were considered I: death due to neurological damage; II: chronic hemodialysis; III: partial renal recovery; IV: complete renal recovery. COMMENTS AND CONCLUSIONS: a/Patients with neurological complications have poor prognosis in spite of minor renal involvement and use of PE whose indication is validated in these cases. b/When renal involvement predominates, accelerated hypertension is linked to arteriolar or mixte type of TMA, exposes to an increased risk of hemorrhagic complications of the renal biopsy (4 out fo 5) which questions the usefulness of such biopsy (group II). c/TMA may precede cancer. It has per se a favorable outcome even when metastases are already present, warranting aggressive treatment.