Potent N-(1,3-thiazol-2-yl)pyridin-2-amine vascular endothelial growth factor receptor tyrosine kinase inhibitors with excellent pharmacokinetics and low affinity for the hERG ion channel

A series of N-(1,3-thiazol-2-yl)pyridin-2-amine KDR kinase inhibitors have been developed that possess optimal properties. Compounds have been discovered that exhibit excellent in vivo potency. The particular challenges of overcoming hERG binding activity and QTc increases in vivo in addition to achieving good pharmacokinetics have been acomplished by discovering a unique class of amine substituents. These compounds have a favorable kinase selectivity profile that can be accentuated with appropriate substitution.     

Role of tumour necrosis factor gene polymorphisms (-308 and -238) in breast cancer susceptibility and severity

Introduction  

Genetic polymorphisms in the promoter region of the tumour necrosis factor (TNF) gene can regulate gene expression and have been associated with inflammatory and malignant conditions. We have investigated two polymorphisms in the promoter of the TNF gene (-308 G>A and -238 G>A) for their role in breast cancer susceptibility and severity by means of an allelic association study.     

The double puncture: an effective percutaneous technique for removing complex, multiple renal calculi

Percutaneous nephrostolithotomy, which can require a double puncture, is presently the method of choice in our institution for the removal of renal stones. Patients that underwent this procedure were evaluated to identify the possible reasons for the double puncture. Of 200 patients evaluated, 14 needed a second tract. The three variables that determined whether a second puncture was needed, in order of importance, were number and size of the stones, with second tracts needed in patients with multiple stones and staghorn calculi; anatomical variations of the renal collecting system itself, with bifid systems the most significant anatomic variation; and the dexterity of the radiologist in performing the puncture and the ability of the urologist to extract the stone. Second tracts were needed more frequently in patients who presented with stones in both the lower and middle poles of the collecting systems.     

Experience with the Amplatz retrievable vena caval filter. Work in progress

The Amplatz retrievable vena caval filter was designed in an attempt to decrease complications associated with the placement of Mobin-Uddin or Kimray-Greenfield filters. The design allows percutaneous retrieval, thus expanding application of the filter to situations requiring temporary prophylaxis against pulmonary embolism. Filters have been placed in 16 patients, nine (56%) for prophylactic purposes. All filters were easily inserted percutaneously. Complications occurred in three patients; these included complete thrombosis of the inferior vena cava below the filter, misplacement of one filter into the pericaval retroperitoneal tissue, and development of thrombus cranial to the filter. With the current introduction system, the possibility of filter misplacement has been essentially eliminated. No patient experienced symptoms suggestive of pulmonary embolism after filter insertion. One filter retrieval has been performed, with no complications.