Alessandro Morettini

Enhanced prostacyclin production by dipyridamole in man

SummaryThe effects of some phosphodiesterase (PDE) inhibitors (dipyridamole, theophylline, papaverine and SH-869) on prostacyclin (PGI2) production have been studied in vitro and in vivo. PGI2 was bioassayed by Vanes superfusion technique. In rabbit aortic rings, only dipyridamole in concentrations from 1 to 12 µM was able to stimulate PGI2 biosynthesis in a dose-dependent manner. This effect was also detected with so-called “exhausted” rabbit aortic rings. The other PDE inhibitors used, both in µM and mM concentration, did not affect PGI2 biosynthesis. Dipyridamole was found to increase PGI2 production in healthy volunteers, when given both by infusion (8 µg/kg/min × 2 h) and by oral administration (375 mg/day for seven days). Circulating PGI2 and PGI2 production induced by a 3-min period of ischaemia were increased by an average of 137% (p<0.001) and 30.8% (p<0.001) respectively. Saline and theophylline (as aminophylline) infusions used as controls did not affect PGI2 production.

Thrombophilic mutations in high-risk atrial fibrillation patients: high prevalence of prothrombin gene G20210A polymorphism and lack of correlation with thromboembolism

Atrial fibrillation (AF) is a common arrhythmia that results in a high risk of cerebral and peripheral embolism. Factor V Leiden and factor II G20210A variant are two leading conditions for venous thrombosis. The aim of our study was to find out whether these two common prothrombotic mutations play a role in the occurrence of embolic events in AF patients. We investigated 336 non-valvular AF patients and 336 healthy control subjects. Factor II G20210A variant was found in 24/336 patients (7.14%) and in 11/336 of control subjects (3.3%). At a multivariate analysis, factor II G20210A variant was independently associated to AF (OR 2.4 95% CI 1.1-5.2; p<0.05). No significant difference was observed in the prevalence of factor V Leiden in the two groups investigated [6/304 (2.0%) in patients vs 13/336 (3.9%) in controls (p=0.24)]. AF patients were separately analyzed in relation to the occurrence or absence of a cerebral or peripheral embolic event (200 with and 136 without embolic event). The prevalence of the two mutations among AF patients with and without an embolic event was similar [factor II G20210A polymorphism (7% and 7.3% respectively) and factor V Leiden (1.2% and 2.9%, respectively)]. No differences were found in relation to the type of embolic event. Our results suggest a possible relationship between the presence of prothrombin gene variant and AF per se.

Role of Prostacyclin and Thromboxane A2 in Ischaemic Heart Disease

Many investigations have shown that cardiac tissue is able to produce prostaglandins (PGs) of D, E, F series and over all prostacyclin (1–3) both in animals and in humans. Much evidence indicates that the primary site of PGs synthesis is the coronary vasculature and not the cardiac myocytes (3,4).

The Valsalva Maneuver in Vasodepressor Syncope

In this work the authors propose the Valsalva maneuver as a diagnostic test in a group of patients shown, by anamnestic, physical, and instrumental crite ria, to be affected by vasodepressor syncope. They studied the response of heart rate and baseline arterial pressure to the maneuver performed in passive orthostasis in 7 healthy volunteers and 24 patients. These patients showed a hypotensive response and a time of recovery to the initial values that was signifi cantly longer than in the control group (p < 0.01). The authors conclude that studying the response to the Valsalva maneuver can be useful in the diagnosis of vasodepressor syncope.

Efficacy of Mexiletine in the Medium-Term Treatment of Ventricular Arrhythmias. A Randomized, Double-Blind, Crossover Trial Against Placebo in Ambulatory Patients

A double-blind, crossover study was designed to compare the safety and efficacy of mexiletine with that of placebo in reducing premature ventricular complexes (PVC) in ambulatory patients and to find out the dose which gives a good therapeutic response with a minimal incidence of side-effects. Twenty-six patients, who had on average 427·9 PVCs/hour, were admitted to the study. The doses given were designed to reduce the frequency of PVCs by 50% or more from the baseline value. Two out of the twenty-six patients stopped treatment because of major side-effects. In the remaining twenty-four patients the 3 weeks of treatment with mexiletine significantly reduced the rate of PVCs by comparison with placebo (-63·8% versus +7·5%). In the nineteen responders (per cent reduction of PVCs over 50%) the dose of mexiletine was 600 mg daily (200 mg every 8 hours). In the non-responders plasma levels of mexiletine proved to be in the therapeutic range, not in any way different from responders. The most frequent side-effects were digestive difficulties (fifteen patients taking mexiletine and six taking placebo). These results show that mexiletine is an effective anti-arrhythmic drug in the management of ventricular arrhythmias occurring in ambulatory patients. In the majority of patients mexiletine was found to be effective even at the lowest dose studied of 600 mg/day.

A prediction rule for early recognition of patients with candidemia in Internal Medicine: results from an Italian, multicentric, case–control study

PurposeIncreasing prevalence of candidemia in Internal Medicine wards (IMWs) has been reported in recent years, but risk factors for candida bloodstream infection in patients admitted to IMW may differ from those known in other settings. The aim of this study was to identify risk factors and define a prediction rule for the early recognition of the risk of candidemia in IMW inpatients.MethodsThis was a multicentric, retrospective, observational case–control study on non-neutropenic patients with candidemia admitted to IMWs of four large Italian Hospitals. Each eligible patient with candidemia (case) was matched to a control with bacteremia. Stepwise logistic regression analyses were performed.ResultsOverall, 300 patients (150 cases and 150 controls) were enrolled. The following factors were associated with an increased risk of candidemia and weighted to build a score: total parenteral nutrition (OR 2.45, p = 0.008; 1 point); central venous catheter (OR 2.19, p = 0.031; 1 point); peripherally inserted central catheter (OR 5.63, p < 0.0001; 3 points), antibiotic treatment prior (OR 2.06; p = 0.059; 1 point) and during hospitalization (OR2.38, p = 0.033; 1 point); neurological disability (OR 2.25, p = 0.01; 1 point); and previous hospitalization within 3 months (OR 1.56, p = 0.163; 1 point). At ROC curve analysis, a final score ≥ 4 showed 84% sensitivity, 76% specificity, and 80% accuracy in predicting the risk of candidemia.ConclusionsThe proposed scoring system showed to be a simple and highly performing tool in distinguishing bloodstream infections due to Candida and bacteria in patients admitted to IMW. The proposed rule might help to reduce delay in empirical treatment and improve appropriateness in antifungal prescription in septic patients.