Phase I and pharmacologic trial of cytosine arabinoside with the selective checkpoint 1 inhibitor Sch 900776 in refractory acute leukemias.

Purpose: Incorporation of cytarabine into DNA activates checkpoint kinase 1 (Chk1), which stabilizes stalled replication forks, induces S-phase slowing, and diminishes cytarabine cytotoxicity. The selective Chk1 inhibitor SCH 900776 abrogates cytarabine-induced S-phase arrest and enhances cytarabine cytotoxicity in acute leukemia cell lines and leukemic blasts in vitro. To extend these findings to the clinical setting, we have conducted a phase I study of cytarabine and SCH 900776.

Three-dimensional in vivo kinematics of an osteoarthritic shoulder before and after total shoulder arthroplasty.

A case of a patient with glenohumeral joint arthritis is presented which demonstrated the three-dimensional shoulder motion before and after total shoulder arthroplasty. Pre-operative shoulder motion differed compared to normal controls, while post-operatively her glenohumeral-to-scapulothoracic motion ratios were restored to near normal ratios.