Novel risk factors for premature peripheral arterial occlusive disease in non-diabetic patients: a case-control study.

BACKGROUND: This study aimed to determine the prevalence of genetic and environmental vascular risk factors in non diabetic patients with premature peripheral arterial disease, either peripheral arterial occlusive disease or thromboangiitis obliterans, the two main entities of peripheral arterial disease, and to established whether some of them are specifically associated with one or another of the premature peripheral arterial disease subgroups. METHODS AND RESULTS: This study included 113 non diabetic patients with premature peripheral arterial disease (diagnosis <45-year old) presenting either a peripheral arterial occlusive disease (N = 64) or a thromboangiitis obliterans (N = 49), and 241 controls matched for age and gender. Both patient groups demonstrated common traits including cigarette smoking, low physical activity, decreased levels of HDL-cholesterol, apolipoprotein A-I, pyridoxal 5'-phosphate (active form of B6 vitamin) and zinc. Premature peripheral arterial occlusive disease was characterized by the presence of a family history of peripheral arterial and carotid artery diseases (OR 2.3 and 5.8 respectively, 95% CI), high lipoprotein (a) levels above 300 mg/L (OR 2.3, 95% CI), the presence of the factor V Leiden (OR 5.1, 95% CI) and the glycoprotein Ia(807T,837T,873A) allele (OR 2.3, 95% CI). In thromboangiitis obliterans group, more patients were regular consumers of cannabis (OR 3.5, 95% CI) and higher levels in plasma copper has been shown (OR 6.5, 95% CI). CONCLUSIONS: According to our results from a non exhaustive list of study parameters, we might hypothesize for 1) a genetic basis for premature peripheral arterial occlusive disease development and 2) the prevalence of environmental factors in the development of thromboangiitis obliterans (tobacco and cannabis). Moreover, for the first time, we demonstrated that the 807T/837T/873A allele of platelet glycoprotein Ia may confer an additional risk for development of peripheral atherosclerosis in premature peripheral arterial occlusive disease.

Comparison of clinical and ultrasonographic evaluations for peripheral synovitis in juvenile idiopathic arthritis.

OBJECTIVES: The characteristics of synovitis in juvenile idiopathic arthritis (JIA) are important to evaluate, as they define several clinical categories. The metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints are frequently involved. Few studies have investigated peripheral joint evaluation using ultrasonography, a sensitive tool for detecting subclinical synovitis. Our objectives here were to compare clinical and ultrasound evaluations of MCP and MTP joint synovitis and to determine the prevalence of predefined ultrasound abnormalities in JIA patients and healthy controls. METHODS: Standardized physical and ultrasound assessments of the same joints were done in 31 consecutive patients with JIA and 41 healthy volunteers. Joint pain, motion limitation, and swelling were recorded. Ultrasonography was performed on the same joints by 2 trained sonographers who recorded synovial fluid, synovial hypertrophy, erosion, and power Doppler signal. Intraobserver reproducibility of ultrasonography was assessed. RESULTS: Of 558 peripheral joints examined in JIA patients, 69 (12.5%) had ultrasonographic synovitis and 83 (15%) had abnormal physical findings. All the physical abnormalities were significantly associated with ultrasonographic synovitis (P < 0.0001) but agreement was low between ultrasonographic and physical findings. Ultrasonographic synovitis was most common at the feet (59.4%), where it was detected clinically in only 25% of cases. Ultrasonographic synovitis was associated with the presence of synovial fluid. Cartilage vascularization was found in 2 (4.2%) healthy controls. CONCLUSION: Ultrasonography is useful for monitoring synovitis in JIA. Subclinical involvement of the MTP joints is common. Clinicians should be aware of the specific ultrasonographic findings in children.

Ultrasonography for detecting enthesitis in juvenile idiopathic arthritis.

OBJECTIVE: Enthesitis is a major feature of juvenile idiopathic arthritis (JIA) but is difficult to diagnose clinically. Our objective was to compare the accuracy of ultrasonography with power Doppler (US-PD) versus clinical examination for diagnosing enthesitis in patients with JIA and healthy controls. METHODS: Twenty-six consecutive patients with JIA and 41 healthy volunteers underwent standardized clinical and US-PD examinations of 5 entheseal sites (proximal and distal quadricepital tendon insertions, Achilles tendon, and plantar fascia). US-PD reproducibility was evaluated. US-PD enthesitis was defined as a PD signal at the enthesis insertion. Bursitis, erosions, and cartilage vascularization were recorded. RESULTS: In the JIA group, 27 (12.5%) of the entheseal sites exhibited clinical enthesitis (distal patellar ligament in 45% of cases) and 20 (9.4%) exhibited US-PD enthesitis (distal patellar tendon in 30%), including 10 clinically normal sites (50%). US-PD enthesitis was found in several patients with oligoarthritis or polyarthritis. Clinical enthesitis (P < 0.0001) and HLA-B27-positive (P = 0.05) status were significantly associated with US-PD enthesitis. Erosion and bursitis, but not tendon thickening, were associated with US-PD enthesitis. US-PD enthesitis was not found at any of the 410 entheseal sites in controls; grade 1 cartilage vascularization was noted at 6% of the control sites. CONCLUSION: Enthesitis is a rare phenomenon in JIA. Clinically silent enthesitis is detected by US-PD and can be found in JIA categories other than enthesitis-related arthritis. Tendon thickening and cartilage vascularization can be detected in healthy controls. These findings may have implications for patient classification of the use of US-PD.

Development of an experimental model of pre-thrombosis in rats based on Wessler's principle using a calibrated venous stasis.

We have developed a model of a pre-thrombotic state in rats based on venous stasis induced by partial ligature of the inferior vena cava. The degree of stenosis was calibrated by using variations in upstream venous pressure. Different degrees of stasis were tested in order to obtain a pre-thrombotic state. Increasing doses of thromboplastin were infused. The thrombogenic potential of this model was evaluated by measuring thrombus weight and by the increase in levels of thrombin-antithrombin complexes. A pre-thrombotic state was induced by 2 h of exposure to a 40% stasis obtained by increasing by 40% the upstream venous pressure (mean thrombus weight, 0.2 +/- 0.6 mg). In these conditions of stasis, low doses of thromboplastin induced venous thrombosis (mean weight, 23 +/- 20 mg; P < 0.05). The increase in thrombus size was correlated to the rise in thrombin-antithrombin levels (r = 0.53, P < 0.001). In conclusion, we have developed the first animal model in which venous stasis can be calibrated by varying the degree of stenosis of the inferior vena cava. This model could be used to study the kinetics of biological markers of hypercoagulability, to study the pathogeny of thrombosis or to evaluate the therapeutic efficacy of new drugs in pre-clinical trials.