Successful term pregnancy after Mustard operation for transposition of the great arteries

Transposition of the great arteries is a complex cardiac malformation with poor prognosis without surgical correction. Since the introduction of surgical procedures such as the intra-auricular reorientation of the venous return (Mustard procedure), an increasing number of patients may reach adulthood and experience pregnancy. Because long-term complications after the Mustard operation include systemic heart failure, arrhythmias, venous return stenosis and pulmonary edema, hemodynamic changes during pregnancy and delivery may potentially engender life-threatening complications in these patients. We report the case of a 24-year-old primigravida who underwent a Mustard procedure at the age of 2 years for transposition of the great vessels, and who carried out a full-term pregnancy. The pregnancy was uneventful until the 34th week, when the woman developed signs of moderate right ventricular failure and frequent episodes of accelerated junctional rhythm. Digitalisation improved symptoms and elicited return to normal sinus rhythm. The patient delivered at term by elective cesarean section, under close hemodynamic monitoring.     

Mercury emission estimates from fires: an initial inventory for the United States

Recent studies have shown that emissions of mercury (Hg), a hazardous air pollutant, from fires can be significant. However, to date, these emissions have not been well-quantified for the entire United States. Daily emissions of Hg from fires in the lower 48 states of the United States (LOWER48) and in Alaska were estimated for 2002-2006 using a simple fire emissions model. Emission factors of Hg from fires in different ecosystems were compiled from published plume studies and from soil-based assessments. Annual averaged emissions of Hg from fires in the LOWER48 and Alaska were 44 (20-65) metric tons yr(-1), equivalent to approximately 30% of the U.S. EPA 2002 National Emissions Inventory for Hg. Alaska had the highest averaged monthly emissions of all states; however, the emissions have a high temporal variability. Emissions from forests dominate the inventory, suggesting that Hg emissions from agricultural fires are not significant on an annual basis. The uncertainty in the Hg emission factors due to limited data leads to an uncertainty in the emission estimates on the order of +/-50%. Research is still needed to better constrain Hg emission factors from fires, particularly in the eastern U.S. and for ecosystems other than forests.     

Effect of chain length on the rate of quaternization of alkyl amines

Trialkyl amines from triethyl to tristearylamine were quaternized with benzyl chloride and compared for the effect of chain length on the rate of quaternization. Triethylamine reacted about twice as fast as tripropylamine with virtually no chain-length effect from propyl to stearyl. Results are compared to previous rate studies on steric hindrance and chain-length dependence.     

Kinetics and preparation of amine oxides

A kinetic model for the oxidation of dimethyllaurylamine to its amine oxide with hydrogen peroxide was developed. It is a second-order reaction where k=.0250, .0079 and .0037 kg per mol/min at 75, 60 and 50°C, respectively. Amine oxides ofN-lauryl morpholine, piperidine and 3-methyl piperidine were synthesized, and their rates of formation were determined. Compared to dimethyllaurylamine, the piperidines react slower, while the morpholine reaction is much faster.     

Transcatheter closure of atrial septal defects within the oval fossa: medium-term results in children using the 'ASDOS'-technique

OBJECTIVES: The purpose of this study was to evaluate the safety and efficacy of the ASDOS-technique (Sulzer-Osypka GmbH, Germany) for transcatheter closure of atrial septal defects within the oval fossa. BACKGROUND: Although several attempts have been made to occlude defects within the oval fossa by transcatheter techniques, none of these has gained general acceptance. METHODS: Patients with a defect in the oval fossa measuring equal to or less than 20 mm diameter, with a residual septal rim of 5 mm or greater, body weight greater than 10 kg, with clinical indications for surgical closure were considered for transcatheter closure. Follow-up investigations were performed at discharge, after 1, 3, 6 and 9 months, as well as after 1 and 2 years. RESULTS: Of 78 patients considered for closure, a device was inserted in 41 patients (53%), with success being achieved in 40 patients (98%). The ages ranged from 1.1 to 15 years (7.8 +/- 1.92 years), the 'stretched' diameter of the defect from 10 to 20 mm (14.7 +/- 2.60 mm), and the diameters of the inserted devices from 25 to 45 mm (33.2 +/- 5.43 mm). Transient impairment of atrioventricular conduction occured in 4 patients. During the follow-up of 23.0 +/- 5.6 months elective surgical closure of a residual shunt was performed 26 months after insertion of the device in one patient. None of the other patients required surgery, hospitalisation or medical treatment, and none is requiring further treatment of the defect within the oval fossa. Fracture of one arm of the device occurred in 4 patients, but the fractured arms are in an unchanged and stable position after a period of at least 19 months. CONCLUSIONS: Our medium-term data show that transcatheter closure in children of defects within the oval fossa can be performed with a high efficacy and safety using the ASDOS-device.     

Long-term electrocardiography. Detection of low-grade myocardial infarction: sensitivity of 9 bipolar leads

The sensitivity of ambulatory electrocardiography (Holter ECG) for detecting ischaemia is relatively low. A case report of an inferior infarction missed by three-lead Holter monitoring that included a modified lead aVF especially places its sensitivity for detecting inferior ischaemia and infarction in question. Therefore, the present study evaluated the sensitivity of nine bipolar Holter leads for detecting isolated inferior Q-wave infarctions, and compared the sensitivity of the modified leads II, III, and aVF of the Holter ECG with the sensitivity of the "corresponding" leads of the standard ECG. METHODS: Sixteen patients, each of whom had a pathological Q-wave (> 0.04 s and > 0.1 mV) in at least two of the three standard ECG leads II, III, and aVF but in none of the other standard leads, were studied for the presence of a pathological Q-wave on the modified Holter leads II, III, aVF, CM2, CM5, CR4, Frank Z, Nehb D, and inverse Nehb J. RESULTS: Of the nine Holter leads, modified lead III provided the highest sensitivity for detecting inferior Q-wave infarctions, followed by lead Frank Z; leads CR 4 and inverse Nehb J were only slightly less sensitive. In contrast, modified leads II and aVF were significantly less sensitive than modified lead III. Modified bipolar lead aVF of the Holter ECG was significantly less sensitive than the "corresponding" lead aVF of the standard ECG, whereas modified leads II and III provided similar sensitivities for detecting inferior Q-wave infarctions as the "corresponding" leads of the standard ECG. CONCLUSIONS: The significantly lower sensitivity of modified lead aVF for detecting inferior Q-wave infarctions compared with standard lead aVF shows that the sensitivity of a Holter ECG lead cannot be deduced from that of the "corresponding" standard ECG lead. Moreover, the significantly higher sensitivity of modified lead III compared with modified leads II and aVF shows that lead selection is important for Holter monitoring.     

Comparison of commercially available quaternary ammonium structures for phase transfer catalysis

A variety of commercially available tetralkyl (R₁R₂R₃R₄N⁺) ammonium chlorides and methyl sulfate salts were examined under phase transfer conditions. For conversion of benzyl chloride to benzyl acetate with aqueous potassium acetate, tri C_8–10 methyl ammonium chloride was the most efficient, with tri C_16–18 methyl ammonium chloride was next. The alkyl trimethyl ammonium chlorides (particularly C_12–14 trimethyl) performed well for the oxidation of benzyl alcohol to benzaldehyde with sodium hypochlorite. Trimethyl tallow, C_16–18 partially unsaturated, ammonium chloride was the catalyst of choice for the dichlorocarbene addition to cyclohexene.     

Discovery and Characterization of ACT‐451840: an Antimalarial Drug with a Novel Mechanism of Action

More than 40 % of the world's population is at risk of being infected with malaria. Most malaria cases occur in the countries of sub‐Saharan Africa, Central and South America, and Asia. Resistance to standard therapy, including artemisinin combinations, is increasing. There is an urgent need for novel antimalarials with new mechanisms of action. In a phenotypic screen, we identified a series of phenylalanine‐based compounds that exhibit antimalarial activity via a new and yet unknown mechanism of action. Our optimization efforts culminated in the selection of ACT‐451840 [(S,E)‐N‐(4‐(4‐acetylpiperazin‐1‐yl)benzyl)‐3‐(4‐(tert‐butyl)phenyl)‐N‐(1‐(4‐(4‐cyanobenzyl)piperazin‐1‐yl)‐1‐oxo‐3‐phenylpropan‐2‐yl)acrylamide] for clinical development. Herein we describe our optimization efforts from the screening hit to the potential drug candidate with respect to antiparasitic activity, drug metabolism and pharmacokinetics (DMPK) properties, and in vivo pharmacological efficacy.