Patients with primary antiphospholipid antibody syndrome and without associated vascular risk factors present a normal endothelial function.

INTRODUCTION: Primary antiphospholipid antibody syndrome (PAPS) is characterized by venous or arterial thrombosis and positive antiphospholipid antibodies. It is controversial whether PAPS patients have early atherosclerosis. Endothelial dysfunction is an early event in the natural history of atherosclerosis. Aim of our study was to compare endothelial function of patients with PAPS and no associated risk factors with that of age- and sex-matched controls. MATERIALS AND METHODS: Patients with PAPS, carefully selected to exclude all known risk factors for cardiovascular diseases, estrogen therapy, pregnancy, intake of drugs affecting endothelial function, vitamins or antioxidants, were included in a case-control study. Controls were age- (+/-5 years) and sex-matched subjects with the same exclusion criteria but without PAPS. Flow-mediated dilation of the brachial artery and some plasmatic markers of endothelial and platelet activation were measured. Measures are expressed as mean+/-SEM. RESULTS: Twenty cases (mean age 42+/-4.0 years, 11 females) and 39 controls (mean age 41+/-2.9, 22 females) were studied. FMD was 5.7+/-0.8% in cases (95% CI: 4.1 to 7.3) and 6.8+/-0.5% (5.7 to 7.9) in controls (p=NS). Plasma von Willebrand factor was 128+/-11.3% and 134.2+/-16.1% in cases and controls, respectively (p=NS). Soluble P-selectin and soluble CD40L were 94.1+/-4.9 ng/ml and 0.7+/-0.1 ng/ml in cases and 87.7+/-4.0 ng/ml and 1.0+/-0.2 in controls, respectively (p=NS). In a substudy, circulating progenitor and mature endothelial cells were comparable between the two groups. CONCLUSIONS: Endothelial function in patients with PAPS and no associated risk factors is similar to that of age- and sex- matched controls. These data suggest that the alterations leading to thrombosis in PAPS concern primarily the clotting system.

Effect of cloricromene on intermittent claudication. A randomized, double-blind, placebo-controlled trial in patients treated with aspirin: effect on claudication distance and quality of life. CRAMPS Investigator Group. Cloricromene Randomized Arteriopathy Multicenter Prospective Study.

The main aim of medical treatment for intermittent claudication (IC) is the reduction of mortality and morbidity from ischemic cardiovascular disease. However, symptomatic treatment with the aim of improving exercise performance and the overall quality of life may also be an important target of the clinical management of patients with intermittent claudication. Cloricromene, a drug with antithrombotic and anti-ischemic activities, has previously shown some promising results in patients with claudication. We have carried out a clinical trial to assess the effect of cloricromene on the claudication distance and on the quality of life of patients with IC chronically treated with aspirin. A total of 159 patients with IC, Stage II (Fontaine), were enrolled in a double-blind, randomized, prospective, multicenter study comparing cloricromene (100 mg orally b.i.d.) or an identical placebo for 6 months. All patients received 160 mg/day aspirin. The primary end-point was the improvement of initial claudication distance (ICD) at 6 months as measured by a standardized treadmill test. The secondary end-points were the absolute claudication distance (ACD) at 6 months, the percentage of patients defined as responders to treatment (improvement of ICD of at least 40%), changes in the ischemic window (IW), quality of life as assessed by the SF-36 questionnaire, and the occurrence of major cardiovascular events. The ICD increased in both treatment groups, with a non-significant difference at 6 months in favor of cloricromene of +12.3 m. The ACD, percentage of responders to treatment and ischemic window also improved in both groups with a slight, non-significant trend in favor of cloricromene. Pretreatment quality of life scores showed only a slight worsening compared with an age-matched, healthy population and did not change upon treatment. A post hoc subgroup analysis showed a significant benefit from cloricromene in patients with an ICD at enrollment higher than the median of the patient population. In conclusion, treatment with cloricromene for 6 months does not significantly improve claudication in patients with Stage II Fontaine peripheral arteriopathy chronically treated with aspirin. An improvement of 40-60 m in the ICD on a standardized treadmill test does not translate into a self-perceived improvement in the quality of life as assessed by the SF-36 questionnaire.

Assessment of occlusion of the vascular access in patients on chronic hemodialysis: comparison of physical examination with continuous-wave Doppler ultrasound. STOP Investigators. Shunt Thrombotic Occlusion Prevention with Picotamide.

BACKGROUND: Dialysis access occlusion is the most common cause of hospitalization and a frequent indirect cause of mortality in patients on chronic hemodialysis. The clinical assessment of an arteriovenous shunt is presently the most widely adopted method for the diagnosis of vascular access occlusion in hemodialysis patients, but no studies have yet investigated objectively its sensitivity and positive predictive value (PPV). Continuous-wave (CW) Doppler ultrasound is a simple, inexpensive, and noninvasive technique for the assessment of arterial blood flow. We have carried out a prospective evaluation of the PPV of CW Doppler for the diagnosis of vascular access occlusion in hemodialysis patients and compared it with clinical investigation. METHODS: Fourty-one hemodialysis patients with clinical diagnosis of occlusion of their fistula were studied, and in 23 of them the diagnosis of occlusion was objectively validated. RESULTS: CW Doppler in the patients in whom occlusion was objectively validated showed PPV of 86 and 83% under basal conditions and after fistula compression, respectively, with sensitivities of 95 and 100%, respectively. Clinical diagnosis, under the same conditions, showed a PPV of 83% and a sensitivity of 100%. CONCLUSIONS: CW Doppler and clinical examination have a similar high sensitivity for the diagnosis of occlusion of the dialysis access; thus, there is no need to use routinely Doppler CW examination, unless objective documentation is required.

Comparability and validity of two clinical scores in the early differential diagnosis of acute stroke.

OBJECTIVE: To compare two available clinical scores for the differential diagnosis of cerebral ischaemia and haemorrhage in acute stroke patients. DESIGN: Prospective, multicentre study of acute stroke patients evaluated with computed tomography and Allen and Siriraj scores; the scores were tested for comparability (kappa statistic) and validity (sensitivity, specificity, positive and negative predictive values, diagnostic gain). The effect of a policy of using Allen and Siriraj scores to determine pathological type of stroke before computed tomography was calculated. SETTING: Three hospitals in Italy, all participating in the international stroke trial, with different access facilities to computed tomography. SUBJECTS: 231 consecutive patients who were screened in the three hospitals for possible inclusion in the international stroke trial from 1 November 1991 to 31 May 1993. RESULTS: The prevalence of haemorrhage (diagnosed with computed tomography) was 14.7% (95% confidence interval 10.1% to 19.3%). Allen scores were "uncertain" in 44 cases and Siriraj scores in 38 cases; in the 164 cases with both the scores in the range of "certainty" kappa was 0.72. Sensitivity, specificity, positive and negative predictive values, and diagnostic gain for haemorrhage were 0.38, 0.98, 0.71, 0.91, and 0.58 for Allen scores and 0.61, 0.94, 0.63, 0.93, and 0.48 for Siriraj scores; positive predictive values for infarction were 91% for Allen scores and 93% for Siriraj scores. According to these data, of 1000 patients with acute stroke, 680 would be correctly and 70 wrongly diagnosed as "ischaemic" with the Allen score; the figures would be 671 and 48 with Siriraj score. CONCLUSION: When computed tomography is not immediately available and the clinician wishes to start antithrombotic treatment (or randomise patients in a clinical trial), the Siriraj score (and possibly the Allen score) can be useful to identify patients at low risk of intracerebral haemorrhage.

Effect of glyceryl trinitrate on distensibility of peripheral muscular arteries in humans is not mediated by prostaglandins.

STUDY OBJECTIVE: Vasodilator prostaglandins have been claimed to be responsible for the coronary haemodynamic and venodilator effects of glyceryl trinitrate, although conflicting results have been reported. The aim of this study was to evaluate whether vasodilator prostaglandins play a role in the effect of glyceryl trinitrate on the distensibility of peripheral muscular arteries in healthy humans. DESIGN: A non-invasive technique, impedance plethysmography, was applied to the assessment of the effects of sublingual glyceryl trinitrate on the compliance of the forearm and digital arteries. The subjects studied received placebo (on two separate occasions), indomethacin (100 mg orally), or ibuprofen (800 mg orally) 1 h before glyceryl trinitrate (0.3 mg sublingual) on four occasions separated from each other by at least 48 h. Blood pressure and heart rate were measured by standard techniques; changes in peripheral arterial compliance were evaluated by impedance plethysmography of the forearm and finger. The study was double blind, cross over, placebo controlled, and randomised. SUBJECTS: 12 healthy male volunteers were enrolled in the study. All subjects were fasting for at least 10 h and had abstained from smoking and from methylxanthine or alcohol containing beverages. MEASUREMENTS AND MAIN RESULTS: Glyceryl trinitrate increased heart rate by 11.6(SEM 1.6) beats.min-1 (p less than 0.0005) and diastolic blood pressure by 8.7(1) mm Hg (p less than 0.01), and decreased systolic blood pressure by 8.7(1.5) mm Hg (p less than 0.01) in placebo treated volunteers; the amplitude of the plethysmograph c wave in the forearm and in the finger was also augmented, by 120(11)% and 78(13)% respectively, indicating an increase in arterial compliance. The results obtained in the two placebo sessions did not differ, indicating good reproducibility of the system. Pretreatment with either indomethacin or ibuprofen did not modify the effects of glyceryl trinitrate on heart rate, blood pressure, and arterial compliance in the forearm and the finger. Both indomethacin and ibuprofen suppressed prostaglandin synthesis, as shown by the striking inhibition of serum TxA2 concentration, by 97.2(1.5)% and 93.7(3.0)%, respectively. CONCLUSIONS: Sublingual glyceryl trinitrate, in doses used clinically, induces a reproducible increase in peripheral arterial compliance in healthy volunteers; prostaglandins do not play any significant role in this effect.

[Picotamide does not interfere with the anticoagulant activity of warfarin in patients wearing heart valve prostheses]. / La picotamide non interferisce con l'attività anticoagulante del warfarin in pazienti portatori di protesi valvolari cardiache.

Picotamide, a new antiplatelet drug which has only slight effects on bleeding time, could be useful, in combination with oral anticoagulants, for the prevention of thromboembolic complications in patients with heart valve prostheses. We have evaluated in a randomized, controlled, double-blind, cross-over study, the effect of picotamide on the anticoagulant activity of warfarin. Administration of 300 mg t.i.d. for 10 days to 10 patients with aortic or mitral valve prostheses did not modify significantly either the level of anticoagulation or the mean daily dosage of warfarin. We observed a trend towards a reduction of plasma levels of beta-thromboglobulin. In conclusion the results of this study show that picotamide does not interfere with the anticoagulant activity of warfarin.