Ryanodine receptor phosphorylation in human heart failure

Heart failure is a complex disorder, characterized by activation of the sympathetic nervous system, leading to dysregulated Ca2+ homeostasis in cardiac myocytes and tissue remodeling. In a variety of diseases, cardiac malfunction is associated with aberrant fluxes of Ca2+ across both the surface membrane and the internal Ca2+ store, the sarcoplasmic reticulum (SR). One prominent hypothesis residues is that in heart failure, the activity of the ryanodine receptor (RyR2) Ca2+ release channel in the SR is increased due to excess phosphorylation and that this contributes to excess SR Ca2+ leak in diastole, reduced SR Ca2+ load and decreased contractility (Huke & Bers, 2008). There is controversy over which serine residues in RyR2 are hyperphosphorylated in animal models of heart failure and whether this is via the CaMKII or the PKA-linked signaling pathway. S2808, S2814 and S2030 in RyR2 have been variously claimed to be hyperphosphorylated. Our aim was to examine the degree of phosphorylation of these residues in RyR2 from failing human hearts. The use of human tissue was approved by the Human Research Ethics Committee, The Prince Charles Hospital, EC28114. Left ventricular tissue samples were obtained from an explanted heart of a patient with endstage heart failure (Emery Dreifuss Muscular Dystrophy with cardiomyopathy) and non-failing tissue was from a patient with cystic fibrosis undergoing heart-lung transplantation with no history of heart disease. SR vesicles were prepared as described by Laver et al. (1995) and examined with SDS-Page and Western Blot. Transferred proteins were probed with antibodies to detect total protein phosphorylation, phosphorylation of RyR2 serine residues S2808, S2814, S2030 and for the key proteins calsequestrin, triadin, junctin and FKBP12.6. To avoid membrane stripping artifact, each membrane was exposed to one phosphorylation-specific antibody and signal densities quantified using Bio-Rad Quantity One software. We found no distinguishable difference between failing and healthy hearts in the protein expression levels of RyR2, triadin, junctin or calsequestrin. We found an expected upregulation of total RyR2 phosphorylation in the failing heart sample, compared to a matched amount of RyR2 (quantified using densiometry) in healthy heart. Probing with antibodies detecting only the phosphorylated form of the specific RyR2 residues showed that the increase in total RyR2 phosphorylation in the failing heart was due to hyperphosphorylation of S2808 and S2814. We found that S2030 phosphorylation levels were unchanged in human heart failure. Interestingly, we found that S2030 has a basal level of phosphorylation in the healthy human heart, different from the absence of basal phosphorylation recently reported in rodent heart (Huke & Bers, 2008). Finally, preliminary results indicate that less FKBP 12.6 is associated with RyR2 in the failing heart, possibly as a consequence of PKA activation. In conclusion, residues S2808 and S2814 are hyperphosphorylated in human heart failure, presumably due to upregulation of the CaMKII and/or PKA signaling pathway as a result of chronic activation of the sympathetic nervous system. Such changes in RyR2 phosphorylation are believed to contribute to the leaky RyR2 phenotype associated with heart failure, which increases the incidence of arrhythmia and contributes to the severely impaired contractile performance of the failing heart. Huke S & Bers DM. (2008). Ryanodine receptor phosphorylation at serine 2030, 2808 and 2814 in rat cardiomyocytes. Biochemical and Biophysical Research Communications 376, 80-85. Laver DR, Roden LD, Ahern GP, Eager KR, Junankar PR & Dulhunty AF. (1995). Cytoplasmic Ca2+ inhibits the ryanodine receptor from cardiac muscle. Journal of Membrane Biology 147, 7-22. Proceedings

The effects of the 2009 dust storm on emergency admissions to a hospital in Brisbane, Australia

In September 2009 an enormous dust storm swept across eastern Australia. Dust is potentially hazardous to health as it interferes with breathing, and previous dust storms have been linked to increased risks of asthma and even death. We examined whether the 2009 Australian dust storm changed the volume or characteristics of emergency admissions to hospital. We used an observational study design, using time series analyses to examine changes in the number of admissions, and case-only analyses to examine changes in the characteristics of admissions. The admission data were from the Prince Charles Hospital, Brisbane, between 1 January 2009 and 31 October 2009. There was a 39% increase in emergency admissions associated with the storm (95% confidence interval: 5, 81%), which lasted for just one day. The health effects of the storm could not be detected using particulate matter levels. We found no significant change in the characteristics of admissions during the storm, specifically there was no increase in respiratory admissions. The dust storm had a short-lived impact on emergency hospital admissions. This may be because the public took effective avoidance measures, or because the dust was simply not toxic, being mainly composed of soil. Emergency departments should be prepared for a short-term increase in admissions during dust storms.

Impact of a data warehouse model for improved decision-making process in healthcare

The health system is one sector dealing with a deluge of complex data. Many healthcare organisations struggle to utilise these volumes of health data effectively and efficiently. Also, there are many healthcare organisations, which still have stand-alone systems, not integrated for management of information and decision-making. This shows, there is a need for an effective system to capture, collate and distribute this health data. Therefore, implementing the data warehouse concept in healthcare is potentially one of the solutions to integrate health data. Data warehousing has been used to support business intelligence and decision-making in many other sectors such as the engineering, defence and retail sectors. The research problem that is going to be addressed is, "how can data warehousing assist the decision-making process in healthcare". To address this problem the researcher has narrowed an investigation focusing on a cardiac surgery unit. This research used the cardiac surgery unit at the Prince Charles Hospital (TPCH) as the case study. The cardiac surgery unit at TPCH uses a stand-alone database of patient clinical data, which supports clinical audit, service management and research functions. However, much of the time, the interaction between the cardiac surgery unit information system with other units is minimal. There is a limited and basic two-way interaction with other clinical and administrative databases at TPCH which support decision-making processes. The aims of this research are to investigate what decision-making issues are faced by the healthcare professionals with the current information systems and how decision-making might be improved within this healthcare setting by implementing an aligned data warehouse model or models. As a part of the research the researcher will propose and develop a suitable data warehouse prototype based on the cardiac surgery unit needs and integrating the Intensive Care Unit database, Clinical Costing unit database (Transition II) and Quality and Safety unit database [electronic discharge summary (e-DS)]. The goal is to improve the current decision-making processes. The main objectives of this research are to improve access to integrated clinical and financial data, providing potentially better information for decision-making for both improved from the questionnaire and by referring to the literature, the results indicate a centralised data warehouse model for the cardiac surgery unit at this stage. A centralised data warehouse model addresses current needs and can also be upgraded to an enterprise wide warehouse model or federated data warehouse model as discussed in the many consulted publications. The data warehouse prototype was able to be developed using SAS enterprise data integration studio 4.2 and the data was analysed using SAS enterprise edition 4.3. In the final stage, the data warehouse prototype was evaluated by collecting feedback from the end users. This was achieved by using output created from the data warehouse prototype as examples of the data desired and possible in a data warehouse environment. According to the feedback collected from the end users, implementation of a data warehouse was seen to be a useful tool to inform management options, provide a more complete representation of factors related to a decision scenario and potentially reduce information product development time. However, there are many constraints exist in this research. For example the technical issues such as data incompatibilities, integration of the cardiac surgery database and e-DS database servers and also, Queensland Health information restrictions (Queensland Health information related policies, patient data confidentiality and ethics requirements), limited availability of support from IT technical staff and time restrictions. These factors have influenced the process for the warehouse model development, necessitating an incremental approach. This highlights the presence of many practical barriers to data warehousing and integration at the clinical service level. Limitations included the use of a small convenience sample of survey respondents, and a single site case report study design. As mentioned previously, the proposed data warehouse is a prototype and was developed using only four database repositories. Despite this constraint, the research demonstrates that by implementing a data warehouse at the service level, decision-making is supported and data quality issues related to access and availability can be reduced, providing many benefits. Output reports produced from the data warehouse prototype demonstrated usefulness for the improvement of decision-making in the management of clinical services, and quality and safety monitoring for better clinical care. However, in the future, the centralised model selected can be upgraded to an enterprise wide architecture by integrating with additional hospital units’ databases.

Investigation of decision making issues in the use of current clinical information systems

Clinical information systems have become important tools in contemporary clinical patient care. However, there is a question of whether the current clinical information systems are able to effectively support clinicians in decision making processes. We conducted a survey to identify some of the decision making issues related to the use of existing clinical information systems. The survey was conducted among the end users of the cardiac surgery unit, quality and safety unit, intensive care unit and clinical costing unit at The Prince Charles Hospital (TPCH). Based on the survey results and reviewed literature, it was identified that support from the current information systems for decision-making is limited. Also, survey results showed that the majority of respondents considered lack in data integration to be one of the major issues followed by other issues such as limited access to various databases, lack of time and lack in efficient reporting and analysis tools. Furthermore, respondents pointed out that data quality is an issue and the three major data quality issues being faced are lack of data completeness, lack in consistency and lack in data accuracy. Conclusion: Current clinical information systems support for the decision-making processes in Cardiac Surgery in this institution is limited and this could be addressed by integrating isolated clinical information systems.

How to Improve Cardiac Surgery Decision Making? In Data Warehousing Perspective

The health system is one sector dealing with very large amount of complex data. Many healthcare organisations struggle to utilise these volumes of health data effectively and efficiently. Therefore, there is a need for very effective system to capture, collate and distribute this health data. There are number of technologies have been identified to integrate data from different sources. Data warehousing is one technology can be used to manage clinical data in the healthcare. This paper addresses how data warehousing assist to improve cardiac surgery decision making. This research used the cardiac surgery unit at the Prince Charles Hospital (TPCH) as the case study. In order to deal with other units efficiently, it is important to integrate disparate data to a single point interrogation. We propose implementing a data warehouse for the cardiac surgery unit at TPCH. The data warehouse prototype developed using SAS enterprise data integration studio 4.2 and data was analysed using SAS enterprise edition 4.3. This improves access to integrated clinical and financial data with, improved framing of data to the clinical context, giving potentially better informed decision making for both improved management and patient care.

Dying feet in ICU : why might extracorporeal membrane oxygenation machines cause necrotic feet?

Background Extracorporeal membrane oxygenation (ECMO) is used for severe lung and/or heart failure in intensive care units (ICU). The Prince Charles Hospital (TPCH) has one of the largest ECMO units in Australia. Its use rapidly increased during the H1N1 (“swine flu”) pandemic and an increase in pedal complications resulted. The relationship between ECMO and pedal complications has been described, particularly in children, though no strong data exists. This paper presents a case series of foot complications in patients having received ECMO treatment. Methods We present nine cases of severe foot complications resulting from patients receiving ECMO treatment at TPCH in 2009–2012. Results Case ages ranged from 16 - 58 years and three were male. Six cases had an unremarkable medical history prior to H1N1 or H1N2 infection, one had Cardiomyopathy, one had received a lung transplant, and one had multi-organ failure post-sepsis. Common medications prescribed included vasopressors, antibiotics, and sedatives. All cases showed signs of markedly impaired peripheral perfusion whilst on ECMO and seven developed increasing areas of foot necrosis. Outcomes include two bilateral below knee amputations, two multiple digital amputations, one Reflex Sympathetic Dystrophy Syndrome, three pressure injuries, and three deaths. Conclusion Necrosis of the feet appears to occur more readily in younger people requiring ECMO treatment than others in ICU. The authors are conducting further studies to investigate associations between particular infections, medical history, medications, or machine techniques and severe foot complications. Some of these early results will also be presented at this conference.

Long-term outcomes following Medtronic Open Pivot valved conduit

Aortic root replacement is a complex procedure, though subsequent modifications of the original Bentall procedure have made surgery more reproducible. The study aim was to examine the outcomes of a modified Bentall procedure, using the Medtronic Open PivotTM valved conduit. Whilst short-term data on the conduit and long-term data on the valve itself are available, little is known of the long-term results with the valved conduit. Patients undergoing aortic root replacement between February 1999 and February 2010, using the Medtronic Open Pivot valved conduit were identified from the prospectively collected Cardiothoracic Register at The Prince Charles Hospital, Brisbane, Australia. All patients were followed up echocardiographically and clinically. The primary end-point was death, and a Cox proportional model was used to identify factors associated.with survival. Secondary end-points were valve-related morbidity (as defined by STS guidelines) and postoperative morbidity. Predictors of morbidity were identified using logistic regression. A total of 246 patients (mean age 50 years) was included in the study. The overall mortality was 12%, with actuarial 10-year survival 79% and a 10-year estimate of valve-related death of 0.04 (95% CI: 0.004, 0.07). Preoperative myocardial infarction (p = 0.004, HR 4.74), urgency of operation (p = 0.038, HR 2.8) and 10% incremental decreases in ejection fraction (p = 0.046, HR 0.69) were predictive of mortality. Survival was also affected by the valve gradients, with a unit increase in peak gradient reducing mortality (p = 0.021, HR 0.93). Valve-related morbidity occurred in 11 patients. Urgent surgery (p <0.001, OR 4.12), aortic dissection (p = 0.015, OR 3.35), calcific aortic stenosis (p = 0.016, OR 2.35) and Marfan syndrome (p 0.009, OR 3.75) were predictive of postoperative morbidity. The reoperation rate was 1.2%. The Medtronic Open Pivot valved conduit is a safe and durable option for aortic root replacement, and is associated with low morbidity and 10-year survival of 79%. However, further studies are required to determine the effect of valve gradient on survival.

Elihu Stone collection undated, 1913-1962.

Collection contains materials pertaining to the life and work of Stone.

Recueil de blasons coloriés des chevaliers de l'Ordre du Saint-Esprit (1579-1581), par J. Bette, sieur d'Angreau.

Dédié au prince Charles, duc de Croy et d'Arschot, qui l'échangea « avecq le sieur de Brunsvic, le 14e en mars 1617. »

« Le Livre des proprietés des choses » [de BARTHOLOMAEUS, Anglicus], traduction de « JEHAN DE CORBICHON ».

Commençant par : « A tres hault et tres puissant prince Charles, le quint de son nom, par la digne pourveance de Dieu... » et finissant par : «... Tulles, Theophile, Varro, Virgilles. Explicit le livre des Proprietés des choses, translatée de latin en françois par Frere Jehan de Corbechan, de l'ordre de St Augustin » .

Recueil de pièces concernant l'Allemagne, et en particulier le Palatinat, et les relations diplomatiques de la France avec l'Allemagne et la Suède, principalement sous le règne de Louis XIII. (1339-1645).

Contient : « Estat particulier de chacun des princes et Estats du sercle de la Basse-Saxe, par M. [Théodore ?] GODEFROY », 1643 ; Pièces concernant les relations de la France et de l'Allemagne, 1551-1552 ; « Discours du Palatinat et de la dignité électorale appartenant au prince Charles-Louis, électeur Palatin du Rhin, contre les prétentions... du duc de Bavière », et autres pièces et mémoires concernant l'affaire de la succession Palatine ; Copies et extraits de diverses pièces, bulles d'or, chartes de rois de Bohême, etc., concernant l'Allemagne et principalement le Palatinat, 1339-1619 ; « Propositions des ambassadeurs du roy de la Grand-Bretagne, de monsieur l'électeur Palatin et duc de Wirtemberg, faictes à Leurs Majestez Très-chrestiennes, touchant l'estat d'Allemagne », et réponse, 1613 ; « Intérests de la Couronne de France au restablissement de la maison électorale Palatine en ses estatz, pays et dignitez » ; Recueil de pièces, traités, lettres, etc., concernant les relations diplomatiques entre la France et l'Allemagne, 1631-1640 (f. 126), — et entre la France et la Suède, 1631-1644 (f. 275) ; « Description de la ville de Munster en Wesphalie..., par le sieur L'ESCALOPIER », aumônier du duc de Longueville, 1645