Volumen 1. Páginas 389-414

Behavior maintained under a second - order schedule by intramuscular injection of morphine or cocaine in rhesus monkeys

Purpose: This phase I study was performed to determine the safety profile, maximum tolerated dose (MTD) and biological activity of lonafarnib (SCH 66336). Single-dose and multi-dose pharmacokinetics were conducted. Methods: Twenty-one patients with advanced solid tumors were enrolled. Each patient received single-dose administration on day 1, cycle 1 then switched to a twice daily (BID) dosing regimen on days 2-14 of a 28-day cycle; subsequent cycles continued BID dosing on days 1-14. Dose-limiting toxicity (DLT) was assessed during the cycle one; toxicity evaluation was closely monitored throughout the treatment. Radiographic scans were completed to assess tumor response. Blood and urine pharmacokinetics were evaluated on days 1 and 14 in cycle 1. SCH 66336- induced farnesylation inhibition was assessed via conversion of prelamin A to lamin in buccal mucosa. Results: DLT and most common...

When COVID-19 began to spread, environmental scientists recognized that the world faced a dangerous upper respiratory viral disease that might exhibit sensitivity to seasonal weather conditions. Many of these scientists have sought to aid COVID-19 response by studying the potential to monitor, forecast, or project disease transmission rates or symptom severity as a function of climate zone, season, meteorological variability, air quality, and other environmental parameters1,2,3,4. The rapid pace of COVID-19 research has meant that studies on this topic appeared on pre-print servers and then on news and social media outlets faster than the information could be cross-checked and peer-reviewed. As many such studies accumulated, it became clear that reported evidence was often contradictory, and in some cases studies were being selected subjectively in a manner that seemed intended to suppor...