Isolated calf deep vein thrombosis in the community setting: the Worcester Venous Thromboembolism study

The prevalence of isolated calf deep vein thrombosis (DVT) in the community setting is relatively unexplored. Confusion remains with regards to its management and contemporary natural history. The purpose of this investigation was to describe the number of cases of calf DVT in the community, use of early management strategies, and rates of venous thromboembolism (VTE) recurrence and major bleeding. The medical records of residents of the Worcester (MA) metropolitan area with ICD-9 codes consistent with potential VTE during 4 study years (1999/2001/2003/2005) were validated by trained nurses. Patient demographic/clinical characteristics, treatment practices, and outcomes were evaluated. Isolated calf DVT was diagnosed in 166 (11.1%) of 1,495 patients with lower extremity DVT. Patients with calf DVT were less likely to be discharged on anticoagulants or with an IVC filter than patients with proximal DVT (84.1 vs. 92.3%). The rates of VTE recurrence and pulmonary embolism did not differ significantly between patients with calf DVT and proximal DVT at 6 months (11.0 vs. 8.7%, 2.6 vs. 1.8%, respectively). Patients with calf DVT had higher adjusted risk of early (14-day) VTE recurrence/extension (OR 2.34, 95% CI 1.01–5.44). Patients with calf DVT had lower rates of major bleeding at 6 months compared to patients with proximal DVT (5.2 vs. 9.3%, P = 0.04). Rates of recurrent VTE and major bleeding following calf DVT in the community are much higher than in randomized clinical trials of patients with proximal or calf DVT. Further study of management strategies for isolated calf DVT is needed.     

Numerical study of water diffusion in biological tissues using an improved finite difference method

An improved finite difference (FD) method has been developed in order to calculate the behaviour of the nuclear magnetic resonance signal variations caused by water diffusion in biological tissues more accurately and efficiently. The algorithm converts the conventional image-based finite difference method into a convenient matrix-based approach and includes a revised periodic boundary condition which eliminates the edge effects caused by artificial boundaries in conventional FD methods. Simulated results for some modelled tissues are consistent with analytical solutions for commonly used diffusion-weighted pulse sequences, whereas the improved FD method shows improved efficiency and accuracy. A tightly coupled parallel computing approach was also developed to implement the FD methods to enable large-scale simulations of realistic biological tissues. The potential applications of the improved FD method for understanding diffusion in tissues are also discussed.     

Comparative pharmacodynamics of keliximab and clenoliximab in transgenic mice bearing human CD4

Keliximab and clenoliximab are monkey/human chimeric CD4 monoclonal antibodies (mAbs) of the IgG1 and IgG4 isotypes, respectively. The pharmacokinetics (PK) and pharmacodynamics (PD) of these mAbs were evaluated in transgenic mice bearing human CD4 molecules on their T cells after a single i.v. administration at three dose levels (5-125 mg/kg). The PK of keliximab and clenoliximab were similar, dose-dependent, and adequately described by a two-compartment model with saturable elimination from both compartments. The enumeration of circulating CD4(+) T cells and density of CD4 on their surface were determined as the PD effects. An indirect response model was proposed to characterize the PD effects. With the increase in mAb dose, the maximum intensity (R(max)) of PD effects was increased, and the time to reach R(max) shifted to later times. At all three dose levels, keliximab caused a relatively rapid decline in the number of circulating CD4(+) T cells, which then recovered gradually. In contrast, clenoliximab at the lowest dose (5 mg/kg) did not produce a significant effect on CD4(+) T cell counts compared with the placebo group. At high doses, clenoliximab caused a significant decrease in the number of CD4(+) T cells. Keliximab appeared to be more potent and efficient in depleting CD4(+) T cells. Both mAbs produced similar down-modulation of CD4 at corresponding dose levels. The findings of this study are consistent with the results of a recent clinical trial that emphasize the importance of this transgenic mouse model for evaluating PK/PD to support clinical development of anti-human CD4 mAbs.