Transvenous (transjugular) liver biopsy

Transvenous (transjugular) liver biopsy consists in taking a liver specimen through a needle introduced into the liver parenchyma from the lumen of a hepatic vein. This procedure was attempted 104 times in 98 patients in whom percutaneous needle liver biopsy was contraindicated because of massive ascites and/or bleeding tendency. A liver specimen was obtained in 100 out of these 104 attempts; the tissue specimens were unfragmented and large enough to allow correct evaluation of liver architecture in 57 biopsies. The procedure was followed by no or only minor complications in all our patients except one who suffered a fatal intraperitoneal hemorrhage in relation to perforation of liver capsule; perforation was due to an excessive front rotation applied to the needle, a maneuver which therefore must be avoided. It is concluded that transvenous liver biopsy is a workable, efficient, and acceptably safe procedure for obtaining liver specimens in patients with massive ascites and/or bleeding tendency.     

Turn-on switch in parathyroid hormone receptor by a two-step parathyroid hormone binding mechanism

Parathyroid hormone (PTH) and its related receptor (PTHR) are essential regulators of calcium homeostasis and bone physiology. PTH activates PTHR by interacting with a ligand-binding site localized within the N-terminal extracellular domain (the N-domain) and the domain comprising the seven transmembrane helices and the connecting extracellular loops (the J-domain). PTH binding triggers a conformational switch in the receptor, leading to receptor activation and subsequent cellular responses. The process of receptor activation occurs rapidly, within approximately 1 s, but the binding event preceding receptor activation is not understood. By recording FRET between tetramethyl-rhodamine in PTH(1-34) and GFP in the N-domain of the receptor, we measured the binding event in real time in living cells. We show that the association time course between PTH(1-34) and PTHR involves a two-step binding process where the agonist initially binds the receptor with a fast time constant (tau approximately 140 ms) and then with slower kinetics (tau approximately 1 s). The fast and slow phases were assigned to hormone association to the receptor N- and J domains, respectively. Our data indicate that the slow binding step to the J-domain coincides with a conformational switch in the receptor, also monitored by FRET between the enhanced cyan fluorescent protein and the enhanced yellow fluorescent protein in the PTHR sensor, PTHR enhanced cyan fluorescent protein/enhanced yellow fluorescent protein (PTHR(CFP/YFP)). These data suggest that the conformational change that switches the receptor into its active state proceeds in a sequential manner, with the first rapid binding step event preceding receptor activation by PTH(1-34).     

Ultrastructure of a late-stage bacterial endocarditis valve vegetation

Journal of Thrombosis and Thrombolysis - Infective endocarditis (IE) remains a severe illness with high mortality rate, despite advances in antibiotic therapy and cardiac surgery. If infectious...     

Development of a primary-care tool to assess treatment success in COPD: consensus report from a closed meeting of respiratory and primary-care specialists.

A 1-day meeting, attended by invited respiratory and primary-care specialists all of whom had an international profile and a specific interest in Chronic Obstructive Pulmonary Disease (COPD), considered specific research recommendations from the Global Initiative in Obstructive Lung Disease (GOLD) workshop report. Attendees discussed developing a tool to complement spirometry and help primary-care physicians assess treatment success in patients with chronic obstructive pulmonary disease. Discussion focused on the requirement of such a tool, and the limitations of existing tools. Proposals followed for a simple, cost-effective checklist for primary-care. This paper is a consensus report of the discussions from the meeting. Decisions reached on the proposed questionnaire were unanimous.