Successful management of multiple permanent pacemaker complications – infection, 13 year old silent lead perforation and exteriorisation following failed percutaneous extraction, superior vena cava obstruction, tricuspid valve endocarditis, pulmonary embolism and prosthetic tricuspid valve thrombosis

A 59 year old man underwent mechanical tricuspid valve replacement and removal of pacemaker generator along with 4 pacemaker leads for pacemaker endocarditis and superior vena cava obstruction after an earlier percutaneous extraction had to be abandoned, 13 years ago, due to cardiac arrest, accompanied by silent, unsuspected right atrial perforation and exteriorisation of lead. Postoperative course was complicated by tricuspid valve thrombosis and secondary pulmonary embolism requiring TPA thrombolysis which was instantly successful. A review of literature of pacemaker endocarditis and tricuspid thrombosis along with the relevant management strategies is presented. We believe this case report is unusual on account of non operative management of right atrial lead perforation following an unsuccessful attempt at percutaneous removal of right sided infected pacemaker leads and the incidental discovery of the perforated lead 13 years later at sternotomy, presentation of pacemaker endocarditis with a massive load of vegetations along the entire pacemaker lead tract in superior vena cava, right atrial endocardium, tricuspid valve and right ventricular endocardium, leading to a functional and structural SVC obstruction, requirement of an unusually large dose of warfarin postoperatively occasioned, in all probability, by antibiotic drug interactions, presentation of tricuspid prosthetic valve thrombosis uniquely as vasovagal syncope and isolated hypoxia and near instantaneous resolution of tricuspid prosthetic valve thrombosis with Alteplase thrombolysis

Discovery of 9-Cyclopropylethynyl-2-((S)-1-[1,4]dioxan-2-ylmethoxy)-6,7-dihydropyrimido[6,1-a]isoquinolin-4-one (GLPG1205), a unique GPR84 negative allosteric modulator undergoing evaluation in a phase II clinical trial

GPR84 is a medium chain free fatty acid-binding G-protein-coupled receptor associated with inflammatory and fibrotic diseases. As the only reported antagonist of GPR84 (PBI-4050) that displays relatively low potency and selectivity, a clear need exists for an improved modulator. Structural optimization of GPR84 antagonist hit 1, identified through high-throughput screening, led to the identification of potent and selective GPR84 inhibitor GLPG1205 (36). Compared with the initial hit, 36 showed improved potency in a guanosine 5′-O-[γ-thio]triphosphate assay, exhibited metabolic stability, and lacked activity against phosphodiesterase-4. This novel pharmacological tool allowed investigation of the therapeutic potential of GPR84 inhibition. At once-daily doses of 3 and 10 mg/kg, GLPG1205 reduced disease activity index score and neutrophil infiltration in a mouse dextran sodium sulfate-induced chronic inflammatory bowel disease model, with efficacy similar to positive-control compound sulfasalazine. The drug discovery steps leading to GLPG1205 identification, currently under phase II clinical investigation, are described herein

The WIPP decision plan: Charting the course for openness in the decision making process

In June of 1989, the Secretary of Energy requested that a plan be developed that would clearly outline the prerequisites to opening the Waste Isolation Pilot Plant (WIPP). It was to provide the basis for a decision making process that was not only visible to the public, but one which included public participation. It must also be dynamic enough to effectively deal with the changing legislative, regulatory, and technical environments. Based on a recognized need for openness, the Secretary`s Draft Decision Plan was developed. The plan charted the course for ultimately making the decision to declare WIPP ready to receive waste for the start of test phase operations. It outlined to critics and supporters alike the rigorous and thorough process by which the internal decisions were made. The plan identified all internal prerequisites to the decision; charted the review cycles, and targeted the completion dates. It also outlined the processes outside the control of the Department, institutional issues, such as legislative land withdrawal, issuance of permits, and designation of transportation routes

Bureauonderzoek : Bouwhuisweg te Nieuwleusen

Projectnr.: P0502223

Stationshus: A Scandinavian influenced approach and design for a strategic multi-modal intervention in Rotterdam South

Rotterdam South the largest problematic neighbourhood in the Netherlands and deals with large social and spatial problems. With the development of a Stationshus a large intervention is made, that connects the area to the national Intercity railway network and that at the same time forms a new centre for Rotterdam South, that connects the physically separated neighbourhoods together. The project contributes to sustainable solutions for the problems in the area and is integrated with respect to the current built environment. Thereby creating a new routes, including a Third City Bridge and the connection between Beijerlandselaan and Laan op Zuid, that help to integrate Rotterdam South further into the city. Centrally a Swedish influenced kulturhus is housed under one roof with the railway station to form the Stationshus, that further contains a library, sports facilities, lecture rooms, kindergarten and commercial activities.Architecture and UrbanismArchitecture and UrbanismArchitecture and The Built Environmen