Long-term management of patients with hypoplastic left heart syndrome: the diagnostic approach at All Children's Hospital

Improved survival in children with hypoplastic left heart syndrome has created a sub-population of children and young adults who are living with functionally univentricular physiology. Routine surveillance with comprehensive screening for structural cardiac disease, functional cardiac disease, arrhythmias, thromboembolic disease, and associated dysfunction of end organs is important. Future directives will better define the plans of care for routine surveillance in patients with hypoplastic left heart syndrome.     

Management of children undergoing cardiac transplantation with high Panel Reactive Antibodies

Highly sensitised children in need of cardiac transplantation have overall poor outcomes because of increased risk for dysfunction of the cardiac allograft, acute cellular and antibody-mediated rejection, and vasculopathy of the cardiac allograft. Cardiopulmonary bypass and the frequent use of blood products in the operating room and cardiac intensive care unit, as well as the frequent use of homografts, have predisposed potential recipients of transplants to allosensitisation. The expansion in the use of ventricular assist devices and extracorporeal membrane oxygenation has also contributed to increasing rates of allosensitisation in candidates for cardiac transplantation. Antibodies to Human Leukocyte Antigen can be detected before transplantation using several different techniques, the most common being the "complement-dependent lymphocytotoxicity assays". "Solid-phase assays", particularly the "Luminex? single antigen bead method", offer improved specificity and more detailed information regarding specificities of antibodies, leading to improved matching of donors with recipients. Allosensitisation prolongs the time on the waiting list for potential recipients of transplantation and increases the risk of complications and death after transplantation. Aggressive reduction of antibodies to Human Leukocyte Antigen in these high-risk patients is therefore of vital importance for long-term survival of the patient and cardiac allograft. Strategies to decrease Panel Reactive Antibody or percent reactive antibody before transplantation include plasmapheresis, intravenous administration of immunoglobulin, and specific treatment to reduce B-cells, particularly Rituximab. These strategies have resulted in varying degrees of success. Antibody-mediated rejection and cardiac allograft vasculopathy are two of the most important complications of transplantation in patients with high Panel Reactive Antibody. The treatment of antibody-mediated rejection in recipients of cardiac transplants is largely empirical and includes the use of high-dose corticosteroids, plasmapheresis, intravenous administration of immunoglobulins, anti-thymocyte globulin, and Rituximab. Cardiac allograft vasculopathy is believed to be secondary to chronic complement-mediated endothelial injury and chronic vascular rejection. The use of proliferation signal inhibitors, such as sirolimus and everolimus, has been shown to delay the progression of cardiac allograft vasculopathy. In some non-sensitised recipients of cardiac transplants, the de novo formation of antibodies to Human Leukocyte Antigen after transplantation may increase the likelihood of adverse clinical outcomes. The use of serial testing for donor-specific antibodies after cardiac transplantation may be advisable in patients with frequent episodes of rejection and patients with history of sensitisation. Allosensitisation before transplantation can negatively influence outcomes after transplantation. A high incidence of antibody-mediated rejection and graft vasculopathy can result in graft failure and decreased survival. Current strategies to decrease allosensitisation have helped to expand the pool of donors, improve times on the waiting list, and decrease mortality. Centres of transplantation offering desensitisation are currently using plasmapheresis to remove circulating antibodies; intravenous immunoglobulin to inactivate antibodies; cyclophosphamide to suppress B-cell proliferation; and Rituximab to deplete B-lymphocytes. Similar approaches are also used to treat antibody-mediated rejection after transplantation with promising results.     

Measuring the rate of progression in Friedreich ataxia: Implications for clinical trial design

Friedreich ataxia is an autosomal recessive neurodegenerative disorder characterized by ataxia of all four limbs, dysarthria, and arreflexia. A variety of measures are currently used to quantify disease progression, including the Friedreich Ataxia Rating Scale, examiner‐rated functional disability scales, self‐reported activities of daily living and performance measures such as the timed 25‐foot walk, 9‐hole pegboard test, PATA speech test, and low‐contrast letter acuity vision charts. This study examines the rate of disease progression over one and two years in a cohort of 236 Friedreich ataxia patients using these scales and performance measure composites. The Friedreich Ataxia Rating Scale and performance‐measure composites captured disease progression, with a greater sensitivity to change over 2 years than over 1 year. The measures differed in their sensitivity to change and in possible bias. These results help to establish norms for progression in FRDA that can be useful in measuring the long‐term success of therapeutic agents and defining sample‐size calculations for double‐blind clinical trials. © 2010 Movement Disorder Society     

Health Professionals: How much Employee Loyalty Should We Expect in a Privatising System?

In recent years UK government policy has been drawing private companies into the operation of the British National Health Service as providers of health care. Hitherto the National Health Service has been the main employer of health care practitioners, but this may change as a result of this development. There is an issue as to whether professional health care practitioners owe the same moral commitment to an employer in the private sector as they would owe to an employer that is part of the state-run National Health Service. I explore some arguments around this issue, focusing on ways of identifying organisational commitment to good health care. With regard to the practitioners commitment to the organisation I consider two strengths of commitment, normative and calculative. I then undertake an analysis of performance, regulatory regimes, and organisational obligations for both sectors. I conclude that while performance and regulatory regimes show little difference between sectors, there is a reasonably compelling argument in favour of a stronger moral commitment to state bodies based on organisational obligations.     

Treatment Patterns and Differences in Survival of Non-Small Cell Lung Cancer Patients Between Academic and Non-Academic Hospitals in the Netherlands

Background

The aims of this study are to analyze differences in survival between academic and non-academic hospitals and to provide insight into treatment patterns for non-small cell lung cancer (NSCLC). Results show the state of NSCLC survival and care in the Netherlands.

Obstetrics during civil war: Six months on a maternity ward in Mallavi,Northern Sri Lanka

A long‐term, large‐scale ethnic armed conflict continues in Sri Lanka, where militant separatists control a northern section of the island. The conflict has resulted in a large population of internally displaced persons and a shortage of medical staff. Drug and equipment shortages compound the difficulty in access to medical care. This article reports the experiences from 1 November 2000 to 30 April 2001 recorded by review of medical records and by interviews, in the peripheral unit, in a separatist controlled area of the Mallavi maternity ward. There were 704 births. Most of the mothers had been displaced by the war (69.5 per cent) and had experienced food shortage (67.5 per cent). Referred patients (18.1 per cent) had a high rate of caesarean section (44.3 per cent) and had travelled a mean of 57.6km to reach Mallavi. There had been substantial antenatal care (94.0 per cent), tetanus toxoid vaccination (95.1 per cent) and malaria prophylaxis (86.4 per cent). Risk factors for low birth weight included a maternal body mass index less than 19 (RR 1.55, CI 1.11–2.16, P=.011), primiparity (RR 1.44, CI 1.05–1.97, P=.024) and self‐reported malarial infection during pregnancy (RR 1.42, CI 1.03–1.97, P=.036). Rates of low birth weight, stillbirths, neonatal deaths and maternal mortality in the Mallavi units were higher than the Sri Lankan national averages. Improvements in quality of care and access to health care are unlikely while the war continues.     

Crystal structure of the precursor of galactose oxidase: an unusual self-processing enzyme.

Galactose oxidase (EC ) is a monomeric enzyme that contains a single copper ion and catalyses the stereospecific oxidation of primary alcohols to their corresponding aldehydes. The protein contains an unusual covalent thioether bond between a tyrosine, which acts as a radical center during the two-electron reaction, and a cysteine. The enzyme is produced in a precursor form lacking the thioether bond and also possessing an additional 17-aa pro-sequence at the N terminus. Previous work has shown that the aerobic addition of Cu(2+) to the precursor is sufficient to generate fully processed mature enzyme. The structure of the precursor protein has been determined to 1.4 A, revealing the location of the pro-sequence and identifying structural differences between the precursor and the mature protein. Structural alignment of the precursor and mature forms of galactose oxidase shows that five regions of main chain and some key residues of the active site differ significantly between the two forms. The precursor structure provides a starting point for modeling the chemistry of thioether bond formation and pro-sequence cleavage.