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Summary Background Vascular Ehlers-Danlos syndrome is a rare severe disease that causes arterial dissections and ruptures that can lead to early death. No preventive treatment has yet been validated. Our aim was to assess the ability of celiprolol, a β 1 -adrenoceptor antagonist with a β 2 -adrenoceptor agonist action, to prevent arterial dissections and ruptures in vascular Ehlers-Danlos syndrome. Methods Our study was a multicentre, randomised, open trial with blinded assessment of clinical events in eight centres in France and one in Belgium. Patients with clinical vascular Ehlers-Danlos syndrome were randomly assigned to 5 years of treatment with celiprolol or to no treatment. Randomisation was done from a centralised, previously established list of sealed envelopes with stratification by patients' age (≤32 years or >32 years). 33 patients were positive for mutation of collagen 3A1 ( COL3A1 ). Celiprolol was administered twice daily and uptitrated every 6 months by steps of 100 mg to a maximum of 400 mg per day. The primary endpoints were arterial events (rupture or dissection, fatal or not). This study is registered with ClinicalTrials.gov, number NCT00190411. Findings 53 patients were randomly assigned to celiprolol (25 patients) or control groups (28). Mean duration of follow-up was 47 (SD 5) months, with the trial stopped early for treatment benefit. The primary endpoints were reached by five (20%) in the celiprolol group and by 14 (50%) controls (hazard ratio [HR] 0·36; 95% CI 0·15–0·88; p=0·040). Adverse events were severe fatigue in one patient after starting 100 mg celiprolol and mild fatigue in two patients related to dose uptitration. Interpretation We suggest that celiprolol might be the treatment of choice for physicians aiming to prevent major complications in patients with vascular Ehlers-Danlos syndrome. Whether patients with similar clinical presentations and no mutation are also protected remains to be established. Funding French Ministry of Health, Programme Hospitalier de Recherche Clinique 2001.

Background —Beraprost sodium (BPS) is a new stable, orally active prostaglandin I 2 analogue with antiplatelet and vasodilating properties. We report the results of a phase III clinical trial of BPS in patients with intermittent claudication. Methods and Results —Patients (n=549) with a pain-free walking distance of between 50 and 300 m were entered into a 4-week single-blind placebo run-in phase. Patients whose pain-free walking distance had changed by 50% in pain-free walking distance at month 6 and in ≥1 earlier treadmill exercise test in the absence of critical cardiovascular events. Success was observed more frequently in the BPS group (43.5%) than in the placebo group (33.3%, P =0.036). Pain-free walking distances increased by 81.5% and 52.5%, respectively, in the BPS and placebo groups ( P =0.001) and maximum walking distances by 60.1% and 35.0%, respectively ( P =0.004). The incidence of critical cardiovascular events was 4.8% in the BPS group and 8.9% in the placebo group. Conclusions —These results show that BPS is an effective symptomatic treatment of patients with intermittent claudication. The beneficial effects of BPS on critical cardiovascular events should be confirmed in appropriate clinical trials.

Thromboangiitis obliterans is defined as an inflammatory disease involving small and medium sized arteries and veins. As no clinical symptoms, signs, radiological or laboratory abnormalities nor pathological features are specific, the diagnosis is usually made according the criteria proposed by Adar in a young smoker, male or female, with distal arterial occlusions sometimes associated with thrombophlebitis and with negative aetiological investigations. Recently, rheumatic manifestations were identified in about 10% of patients. If new developments in vascular medicine, as ultrasound explorations or CT scan limit the indications for angiography, others, especially in the field of thrombophilia, make more difficult the differential diagnosis. If the strong link between the disease activity and smoking habits is confirmed, medical or surgical approach remain disappointing. Takayasu's disease or non specific aorto-arteritis is an inflammatory disease of young women that primarily affects the aorta its main branches and the pulmonary arteries. The disease often start in children. The prevalence of the disease as the arterial lesions show geographical variations. That and the different associations with infectious, rheumatic or systemic diseases could justify to consider Takayasu's disease as a syndrome. B-mode ultrasonography and electron beam computed tomography are usually sufficient to characterize the arterial involvement and are essential for the follow up of patients. In some rare cases arterial biopsy is necessary to confirm the diagnosis. The surgical treatment concerns specific lesions with ischemic symptoms and failure of the medical approach, however endovascular techniques are often discussed in first intention. During inflammatory phases with evolutive lesions corticosteroids are often used. In case of failure cyclophosphamide or methotrexate have been used.

tients with acute venousthromboembolismconsistsof5to7daysofunfractionatedheparinorlow-molecular-weighthep-arin,overlappedwithandfollowedbylong-term oral anticoagulation with avitamin K antagonist such as warfa-rin. Heparins must be given parenter-ally, and their administration requiresconsiderable health care resources.Warfarinhasanunpredictabledosere-sponse,interactswithmanydrugs,andcanbeaffectedbychangesindiet;thus,continuedcoagulationmonitoringanddose adjustment are necessary.

delineated by Parks et a1.6 include (1) the tense, woody fibrosis; (2) irregularly shaped ulcers, some extending to expose muscle; (3) a halo of'hyperpigmentaion surrounding the ulcers; and (4) the apparent indifference of the patients toward the disfiguring process and their lack of expression of pain despite the degree of tissue destruction. Several reports have described the typical pentazocine abuser as middle-aged, college-educated, married, and associated with the health professions." Often there is a history of alcohol or drug abuse or psychiatric illness.Patients with a personal or family history of diabetes may also be at special risk for cutaneous complications' The exact mechanism by which injection of pentazocine induces cutaneous and muscle changes is unknown. There is histologic evidence of vascular thrombosis with dermal and epidermal infarction." Other authors'' postulate that precipitation of pentazocine in tissue incites an inflammatory response.