Smoking cessation therapy with varenicline.

Smoking cessation is the only available intervention proven to halt progression of chronic obstructive pulmonary disease (COPD). The authors discuss the current existing treatment modalities and the role of a newly approved agent, varenicline, in promotion of smoking cessation. Varenicline is a novel agent that is a centrally acting partial nicotinic acetylcholine receptor agonist. It has both agonistic and antagonistic properties that together are believed to account for reduction of craving and withdrawal as well as blocking the rewarding effects of smoking. Its targeted mechanism of action, better efficacy and tolerability makes varenicline a useful therapeutic option for smoking cessation. In this article, we discuss presently available options for smoking cessation and review the literature on efficacy of varenicline.

Neurotensin increases mortality and mast cells reduce neurotensin levels in a mouse model of sepsis.

Sepsis is a complex, incompletely understood and often fatal disorder, typically accompanied by hypotension, that is considered to represent a dysregulated host response to infection. Neurotensin (NT) is a 13-amino-acid peptide that, among its multiple effects, induces hypotension. We find that intraperitoneal and plasma concentrations of NT are increased in mice after severe cecal ligation and puncture (CLP), a model of sepsis, and that mice treated with a pharmacological antagonist of NT, or NT-deficient mice, show reduced mortality during severe CLP. In mice, mast cells can degrade NT and reduce NT-induced hypotension and CLP-associated mortality, and optimal expression of these effects requires mast cell expression of neurotensin receptor 1 and neurolysin. These findings show that NT contributes to sepsis-related mortality in mice during severe CLP and that mast cells can lower NT concentrations, and suggest that mast cell-dependent reduction in NT levels contributes to the ability of mast cells to enhance survival after CLP.

Interval from prostate biopsy to radical prostatectomy: effect on PSA, Gleason sum, and risk of recurrence.

OBJECTIVES: To determine whether the change in prostate-specific antigen (PSA), change in Gleason sum, and/or interval between prostate biopsy and radical prostatectomy have an association with biochemical recurrence. METHODS: The relationship between biochemical recurrence and the interval between biopsy and surgery, as well as the rate and amount of change in PSA and Gleason sum from biopsy to surgery, was evaluated in 151 patients with prostate cancer treated with radical prostatectomy. RESULTS: A statistically significant increase was found in PSA level and Gleason sum between biopsy and surgery (P = 0.01 and P < 0.0001, respectively). No significant association was found between prebiopsy PSA level (P = 0.27) or biopsy Gleason sum (P = 0.07) with biochemical recurrence as independent variables or in a combined model (P = 0.12). An association was also not found between recurrence and preprostatectomy PSA level (P = 0.15) or the rate of PSA change (P = 0.28) as independent variables. However, a significant association was found with the prostatectomy Gleason sum (P = 0.001). In a combined model, a significant association was noted between the preprostatectomy PSA level and prostatectomy specimen Gleason sum and biochemical recurrence (P = 0.003). No increased risk of biochemical recurrence was noted with increasing time from biopsy to prostatectomy (odds ratio 1.00) or the rate (odds ratio 1.03) and degree (odds ratio 1.30) of serum PSA or Gleason sum (odds ratio 1.07). CONCLUSIONS: The interval between biopsy and radical prostatectomy is not a predictor of biochemical failure. An association was noted between an increased risk of biochemical failure and the amount of serum PSA and Gleason sum increase between biopsy and surgery.