The effect of Bosentan on exercise capacity in Fontan patients:rationale and design for the TEMPO study

BACKGROUND: Palliative treatment with the Fontan procedure has greatly improved survival for children with functionally univentricular heart. Since Fontan performed the first successful operation, the procedure has evolved and is now performed as Total Cavo-Pulmonary Connection (TCPC). An increasing prevalence and longer life expectancy of TCPC patients have raised new challenges. The survivors are often suffering complications such as arrhythmias, myocardial dysfunction, thromboembolic events, neuropsychological deficit, protein-losing enteropathy and reduced exercise capacity. Several causes for the reduced exercise capacity may be present e.g. impaired function of the single ventricle, valve dysfunction and chronotropic impairment, and perhaps also increased pulmonary vascular resistance. Thus, plasma endothelin-1 has been shown to correlate with increased pulmonary vascular resistance and the risk of failing Fontan circulation. This has raised the question of the role for pulmonary vasodilation therapy, especially endothelin receptor antagonist in the management of TCPC patients. METHODS/DESIGN: The TEMPO trial aims to investigate whether Bosentan, an endothelin receptor antagonist, can be administered safely and improve exercise capacity in TCPC patients. The trial design is randomized, double-blind and placebo-controlled. Bosentan/placebo is administered for 14 weeks with control visits every four weeks. The primary endpoint is change in maximal oxygen consumption as assessed on bicycle ergometer test. Secondary endpoints include changes in pulmonary blood flow during exercise test, pro brain natriuretic peptide and quality of life. DISCUSSION: We hypothesize that treatment with Bosentan, an endothelin receptor antagonist, can be administered safely and improve exercise capacity in TCPC patients. TRIAL REGISTRATION: clinicaltrials.gov NCT0129255

A Comparison of Three Occur-Check Analysers

A well known problem of most Prolog interpreters and compilers is the lack of occur-check in the implementation of the unification algorithm. This means that such systems are unsound with respect to first-order predicate logic. Static analysis offers an appealing approach to the problem of occur-check reduction, that is, how to safely omit occur-checks in unification. We compare, for the first time, three static methods that have been suggested for occur-check reduction, two based on assigning "modes" to programs and one which uses abstract interpretation. In each case, the analysis or some essential part of it had not been implemented so far. Of the mode-based methods, one is due to Chadha and Plaisted and the other is due to Apt and Pellegrini. The method using abstract interpretation is based on earlier work by Plaisted, Søndergaard and others who have developed "groundness" and "sharing" analyses for logic programs. The conclusion is that a truly global analysis based on abstract i..