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Hyperfibrinolysis is a systemic condition occurring in various clinical disorders such as trauma, liver cirrhosis, and leukemia. Apart from increased bleeding tendency, the pathophysiological consequences of hyperfibrinolysis remain largely unknown. Our aim was to develop an experimental model of hyperfibrinolysis and to study its effects on the homeostasis of the blood-brain barrier (BBB). We induced a sustained hyperfibrinolytic state in mice by hydrodynamic transfection of a plasmid encoding for tissue-type plasminogen activator (tPA). As revealed by near-infrared fluorescence imaging, hyperfibrinolytic mice presented a significant increase in BBB permeability. Using a set of deletion variants of tPA and pharmacological approaches, we demonstrated that this effect was independent of N-methyl-D-aspartate receptor, low-density lipoprotein-related protein, protease-activated receptor-1, or matrix metalloproteinases. In contrast, we provide evidence that hyperfibrinolysis-induced BBB leakage is dependent on plasmin-mediated generation of bradykinin and subsequent activation of bradykinin B2 receptors. Accordingly, this effect was prevented by icatibant, a clinically available B2 receptor antagonist. In agreement with these preclinical data, bradykinin generation was also observed in humans in a context of acute pharmacological hyperfibrinolysis. Altogether, these results suggest that B2 receptor blockade may be a promising strategy to prevent the deleterious effects of hyperfibrinolysis on the homeostasis of the BBB., (© 2016 by The American Society of Hematology.)

In a prospective, open study, 78 patients with terminal cancer received proctoclysis (rectal hydration) in four different centers. In all cases, a #22 French nasogastric catheter was inserted approximately 40 cm into the rectum and an infusion of normal saline (2 cases) or tap water (76 cases) was administered at a rate of 250 +/- 63 cc/hr. Hydration was maintained for 15 +/- 8 days. The main reason for discontinuation of hydration was death (60 cases). The mean visual analogue score for discomfort after infusion (0 = no discomfort, 100 = worst possible discomfort) was 19 +/- 14. The costs of proctoclysis was estimated at Can$0.08 compared with Can$4.56 per day for hypodermoclysis, and Can$2.78 per day for intravenous hydration. Our results suggest that proctoclysis is a safe, effective, and low-cost technique for the delivery of hydration in terminally ill cancer patients.

Fourteen patients with advanced cancer received intermittent subcutaneous injection of morphine using an Edmonton Injector (EI). Twelve patients used the system at home. The minimal dose of morphine was 15 mg every 4 hr and the maximal dose was 90 mg every 4 hr. There were two complications: abscess and bleeding. In developing countries, the safety, low cost, and versatility of the Edmonton Injector offers an important alternative in terminally ill patients. This device is an ideal "injection pump" for use in developing countries, where costs are most important in making treatment decisions.