Long Term Consequences of the Fontan Procedure and How to Manage Them

In 1971, Fontan and Baudet described a surgical technique for successful palliation of patients with tricuspid atresia. Subsequently, this technique has been applied to treat most forms of functional single ventricles and has become the current standard of care for long-term palliation of all patients with single ventricle congenital heart disease. Since 1971, the Fontan procedure has undergone several variations. These patients require lifelong management including a thorough knowledge of their anatomic substrate, hemodynamic status, management of rhythm and ventricular function along with multi organ evaluation. As these patients enter middle age, there is increasing awareness regarding the long-term complications and mortality. This review highlights the long-term outcomes of the Fontan procedure and management of late sequelae

The Prevalence of Natural Health Product Use in Patients with Acute Cardiovascular Disease

Background: Natural health products (NHP) use may have implications with respect to adverse effects, drug interactions and adherence yet the prevalence of NHP use by patients with acute cardiovascular disease and the best method to ascertain this information is unknown. Objective: To identify the best method to ascertain information on NHP, and the prevalence of use in a population with acute cardiovascular disease. Methods: Structured interviews were conducted with a convenience sample of consecutive patients admitted with acute cardiovascular disease to the University of Alberta Hospital during January 2009. NHP use was explored using structured and open-ended questions based on Health Canada’s definition of NHP. The medical record was reviewed, and documentation of NHP use by physicians, nurses, and pharmacists, compared against the gold-standard structured interview. Results: 88 patients were interviewed (mean age 62 years, standard deviation [SD 14]; 80 % male; 41 % admitted for acute coronary syndromes). Common co-morbidities included hypertension (59%), diabetes (26%) and renal impairment (19%). NHP use was common (78 % of patients) and 75 % of NHP users reported daily use. The category of NHP most commonly used was vitamins and minerals (73%) followed by herbal products (20%), traditional medicines including Chines

Results of an Expert Consensus Survey on the Treatment of Pulmonary Arterial Hypertension With Oral Prostacyclin Pathway Agents

Background Treatment of pulmonary arterial hypertension (PAH) has evolved substantially over the past two decades and varies according to etiology, functional class (FC), hemodynamic parameters, and other clinical factors. Current guidelines do not provide definitive recommendations regarding the use of oral prostacyclin pathway agents (PPAs) in PAH. To provide guidance on the use of these agents, an expert panel was convened to develop consensus statements for the initiation of oral PPAs in adults with PAH. Methods A systematic literature search was conducted using MEDLINE. The established RAND/University of California Los Angeles appropriateness method, which incorporates the Delphi method and the nominal group technique, was used to create consensus statements. Idiopathic, heritable, repaired congenital heart defect, and drug- or toxin-induced PAH (IPAH+) was considered as one etiologic grouping. The process was focused on the use of oral treprostinil or selexipag in patients with IPAH+ or connective tissue disease-associated PAH and FC II or III symptoms receiving background dual endothelin receptor antagonist/phosphodiesterase type 5 inhibitor therapy. Results The panel developed 14 consensus statements regarding the appropriate use of oral PPAs in the target population. The panel identified 13 clinical scenarios in which selexipag may be considered as a treatment option. Conclusions The paucity of clinical evidence overall, and particularly from randomized trials in this setting, creates a gap in knowledge. These consensus statements are intended to aid physicians in navigating treatment options and using oral PPAs in the most appropriate manner in patients with PAH

Innovations and advances in instrumentation at the W. M. Keck Observatory

Since the start of operations in 1993, the twin 10 meter W. M. Keck Observatory telescopes have continued to maximize their scientific impact and to produce transformative discoveries that keep the observing community on the frontiers of astronomical research. Upgraded capabilities and new instrumentation are provided though collaborative partnerships with Caltech and UC instrument development teams. The observatory adapts and responds to the observers’ evolving needs as defined in the observatory’s strategic plan, periodically refreshed in collaboration with the science community. This paper summarizes the performance of recently commissioned infrastructure projects, technology upgrades, and new additions to the suite of instrumentation at the observatory. We will also provide a status of projects currently in the design or development phase, and since we need to keep our eye on the future, we mention projects in exploratory phases that originate from our strategic plan. Recently commissioned projects include telescope control system upgrades, OSIRIS spectrometer and imager upgrades, and deployments of the Keck Cosmic Web Imager (KCWI), the Near-Infrared Echellette Spectrometer (NIRES), and the Keck I Deployable Tertiary Mirror (KIDM3). Under development are upgrades to the NIRSPEC instrument and adaptive optics (AO) system. Major instrumentation in design phases include the Keck Cosmic Reionization Mapper and the Keck Planet Finder. Future instrumentation studies and proposals underway include a Ground Layer Adaptive Optics system, NIRC2 upgrades, the energy sensitive instrument KRAKENS, an integral field spectrograph LIGER, and a laser tomography AO upgrade. Last, we briefly discuss recovering MOSFIRE and its return to science operations

Characterization of PTZ-Induced Seizure Susceptibility in a Down Syndrome Mouse Model That Overexpresses CSTB

Down syndrome (DS) is a complex genetic syndrome characterized by intellectual disability, dysmorphism and variable additional physiological traits. Current research progress has begun to decipher the neural mechanisms underlying cognitive impairment, leading to new therapeutic perspectives. Pentylenetetrazol (PTZ) has recently been found to have positive effects on learning and memory capacities of a DS mouse model and is foreseen to treat DS patients. But PTZ is also known to be a convulsant drug at higher dose and DS persons are more prone to epileptic seizures than the general population. This raises concerns over what long-term effects of treatment might be in the DS population. The cause of increased propensity for epilepsy in the DS population and which Hsa21 gene(s) are implicated remain unknown. Among Hsa21 candidate genes in epilepsy, CSTB, coding for the cystein protease inhibitor cystatin B, is involved in progressive myoclonus epilepsy and ataxia in both mice and human. Thus we aim to evaluate the effect of an increase in Cstb gene dosage on spontaneous epileptic activity and susceptibility to PTZ-induced seizure. To this end we generated a new mouse model trisomic for Cstb by homologous recombination. We verified that increasing copy number of Cstb from Trisomy (Ts) to Tetrasomy (Tt) was driving overexpression of the gene in the brain, we checked transgenic animals for presence of locomotor activity and electroencephalogram (EEG) abnormalities characteristic of myoclonic epilepsy and we tested if those animals were prone to PTZ-induced seizure. Overall, the results of the analysis shows that an increase in Cstb does not induce any spontaneous epileptic activity and neither increase or decrease the propensity of Ts and Tt mice to myoclonic seizures suggesting that Ctsb dosage should not interfere with PTZ-treatment