Hydroxocobalamin to treat refractory vasoplegia following phaeochromocytoma resection in a child.

Phaeochromocytomas and paragangliomas are rare neuroendocrine tumours that often secrete catecholamines, which can cause dramatic swings in blood pressure and end-organ damage. During surgical resection of these tumours, antihypertensive drug infusions are often required, but after resection patients may become vasoplegic, in part due to cessation of catecholamine secretion by the tumour in the context of pre-operative α1 adrenoceptor antagonism. Numerous medications have been used to treat vasoplegia in this setting, including noradrenaline, vasopressin and, more recently, angiotensin II. We report the case of a patient who experienced vasoplegia after phaeochromocytoma resection which was refractory to vasopressin and angiotensin II infusions but was successfully treated with high dose hydroxocobalamin.

AXL induces epithelial-to-mesenchymal transition and regulates the function of breast cancer stem cells.

Despite significant progress in the treatment of breast cancer, particularly through the use of targeted therapy, relapse and chemoresistance remain a major hindrance to the fight to minimize the burden of the disease. It is becoming increasingly clear that a rare subpopulation of cells known as cancer stem cells (CSC), able to be generated through epithelial-to-mesenchymal transition (EMT) and capable of tumor initiation and self-renewal, contributes to treatment resistance and metastases. This means that a more effective therapy should target both the chemoresistant CSCs and the proliferating epithelial cells that give rise to them to reverse EMT and to attenuate their conversion to CSCs. Here, we demonstrate a novel function of AXL in acting upstream to induce EMT in normal and immortalized human mammary epithelial cells in an apparent positive feedback loop mechanism and regulate breast CSC (BCSC) self-renewal and chemoresistance. Downregulation of AXL using MP470 (Amuvatinib) reversed EMT in mesenchymal normal human mammary epithelial cells and murine BCSCs attenuating self-renewal and restored chemosensitivity of the BCSCs. AXL expression was also found to be associated with the expression of stem cell genes, regulation of metastases genes, increased tumorigenicity and was important for BCSC invasion and migration. Inactivation of AXL also led to the downregulation of nuclear factor-κB pathway and reduced tumor formation in vivo. Taken together, our data suggest that targeted therapy against AXL, in combination with systemic therapies, has the potential to improve response to anticancer therapies and to reduce breast cancer recurrence and metastases.

Disposition of cefoxitin in patients with ascites.

The pharmacokinetics of Cefoxitin was studied in 8 cirrhotic patients with ascites after i.v. administration of a single 30 mg/kg dose. Concentrations of cefoxitin in serum and in ascitic fluid were determined simultaneously and by a microbiologic plate diffusion method. The antibiotic followed a two-compartment open kinetic model. In ascitic fluid, Cefoxitin reached its maximum concentration of 32.80 +/- 13,78 micrograms/ml 2 h after administration. The mean elimination constant from ascitic fluid was 0.201 +/- 0.008 h(-1), significantly lower (p less than 0.05) than the slow disposition phase constant (beta = 0.556 +/- 0.17 h(-1)). At the dose studied and with a dosage interval of 8 h, the level of antibiotic in the ascitic fluid would be maintained at a value greater than the MIC of most cefoxitin-sensitive organisms.