Publications by authors named "Peter O'Callaghan"

This study aims to assess the epidemiology, clinical presentation, management, and outcomes of pediatric Wolff-Parkinson-White (WPW) syndrome, as well as the incidence of life-threatening events (LTE) in South Wales. Retrospective review of patients (< 17 years old) diagnosed with WPW syndrome between 1986 and 2019 in South Wales. The study population consisted of 160 patients, of whom 86 (54%) were male.

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The rare dermatological condition X-linked ichthyosis (XLI) is associated with a substantially-increased risk of cardiac arrhythmias. Arrhythmias predispose to multiple serious health conditions, and there is a need to identify them at an early stage, ideally using non-invasive, convenient, cost-effective, and reliable wearable technology methods. We tested the feasibility of monitoring heart rhythms using an Apple Watch in five adult males from the United Kingdom diagnosed with XLI.

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Background: When cardiac implantable electronic device infection occurs, standard therapy is usually total system extraction. Transvenous lead extraction is preferable to open heart surgical extraction, unless contraindicated because of the presence of very large vegetations on the intravenous leads according to the European Society of Cardiology guidelines. Extraction of transvenous leads with vegetations risks distal embolism resulting in obstruction and/or infection in the pulmonary arteries.

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Background: Non-islet cell tumour hypoglycemia (NICTH) is rarely encountered in clinical practice. Insulin-like growth factor 2 (IGF2) is the most common cause of NICTH observed in the setting of mesenchymal and epithelial neoplasia. This is a paraneoplastic syndrome caused by IGF2 activation of the insulin receptor.

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A multivariate risk score model was proposed by Sieira et al in 2017 for sudden death in Brugada syndrome; their validation in 150 patients was highly encouraging, with a C-index of 0.81; however, this score is yet to be validated by an independent group. A total of 192 records of patients with Brugada syndrome were collected from 2 centers in the United Kingdom and retrospectively scored according to a score model by Sieira et al.

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Background: This is the first case report demonstrating the use of a smartphone device, enabling the diagnosis of an arrhythmia in the sports cardiology literature.

Case Summary: A 17-year-old semi-professional rugby player presented with recurrent episodes of palpitations terminated by vagal manoeuvres. The rugby player's resting 12-lead electrocardiogram (ECG), echocardiogram, and exercise stress test were normal.

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Article Synopsis
  • Temporary cardiac pacing using externalized prolonged temporary pacing (EPTP) can be a safe alternative to traditional methods, especially for patients who can't have permanent pacemakers due to conditions like sepsis.
  • In a study of 67 patients averaging 69 years old, EPTP was usually used for serious heart rhythm issues and was effective, with a mean pacing duration of 16 days.
  • The results showed good outcomes, with 63% of patients receiving permanent devices afterward and no significant complications related to EPTP, indicating its usefulness in critical care scenarios.
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Chinese hamster ovary (CHO) cell lines are the pillars of a multibillion-dollar biopharmaceutical industry producing recombinant therapeutic proteins. The effects of local chromatin organization and epigenetic repression within these cell lines result in unpredictable and unstable transgene expression following random integration. Limited knowledge of the CHO genome and its higher order chromatin organization has thus far impeded functional genomics approaches required to tackle these issues.

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The objective of this study was to determine whether a single session of exercise was sufficient to induce cerebral adaptations in individuals with Huntington's disease and to explore the time dynamics of any acute cerebrovascular response. In this case-control study, we employed arterial-spin labelling MRI in 19 Huntington's disease gene-positive participants (32-65 years, 13 males) and 19 controls (29-63 years, 10 males) matched for age, gender, body mass index and self-reported activity levels, to measure global and regional perfusion in response to 20 min of moderate-intensity cycling. Cerebral perfusion was measured at baseline and 15, 40 and 60 min after exercise cessation.

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Background: Last year, there were 2,000 out-of-hospital cardiac arrests (OHCA) in New Zealand, 74% received CPR but only 5.1% accessed an automated external defibrillator (AED). The average survival rate of OHCA is 13%.

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Much effort has been expended to improve the capabilities of individual Chinese hamster ovary (CHO) host cell lines to synthesize recombinant therapeutic proteins (rPs). However, given the increasing variety in rP molecular types and formats it may be advantageous to employ a toolbox of CHO host cell lines in biomanufacturing. Such a toolbox would contain a panel of hosts with specific capabilities to synthesize certain molecular types at high volumetric concentrations and with the correct product quality (PQ).

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Aim: To assess the feasibility of administering Patient Reported Outcomes Measures (PROMs) in patients treated with ablation for cardiac arrhythmias, and to conduct the first stage of development and testing of a new PROM tool.

Methods And Results: A new tool was developed by a multidisciplinary team and tested alongside an adaptation of the patient perception of arrhythmia questionnaire (PPAQ) and EQ-5D-5L in a multicentre retrospective audit involving 791 consecutive cardiac arrhythmia patients treated with catheter ablation at three UK centres over 13 months. Data were recorded in the National Cardiac Rhythm Management Database, part of the National Institute for Cardiovascular Outcomes Research.

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Clinicians who diagnose and manage epilepsy frequently encounter diagnoses of a nonneurological nature, particularly when assessing patients with transient loss of consciousness (T-LOC). Among these, and perhaps the most important, is cardiac syncope. As a group, patients with cardiac syncope have the highest likelihood of subsequent sudden death, and yet, unlike sudden unexpected death in epilepsy (SUDEP) for example, it is the norm for these tragic occurrences to be both easily predictable and preventable.

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In this study, we systematically compare two vector design strategies for recombinant monoclonal antibody (Mab) synthesis by Chinese hamster ovary (CHO) cells; a dual open reading frame (ORF) expression vector utilizing separate cytomegalovirus (CMV) promoters to drive heavy chain (HC) and light chain (LC) expression independently, and a single ORF vector design employing a single CMV promoter to drive HC and LC polypeptide expression joined by a foot and mouth disease virus F2A polypeptide self-cleaving linker sequence. Initial analysis of stable transfectants showed that transfectants utilizing the single ORF vector designs exhibited significantly reduced Mab production. We employed an empirical modeling strategy to quantitatively describe the cellular constraints on recombinant Mab synthesis in all stable transfectants.

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One of the most significant problems in industrial bioprocessing of recombinant proteins using engineered mammalian cells is the phenomenon of cell line instability, where a production cell line suffers a loss of specific productivity (qP). This phenomenon occurs with unpredictable kinetics and has been widely observed in Chinese hamster ovary (CHO) cell lines and with all commonly used gene expression systems. The underlying causes (both genetic and physiological) and the precise molecular mechanisms underpinning cell line instability have yet to be fully elucidated, although recombinant gene silencing and loss of recombinant gene copies have been shown to cause qP loss.

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Article Synopsis
  • The study combined mathematical models to analyze factors limiting monoclonal antibody production in GS-CHO cells during an industrial culture process.
  • The major limitations identified were in the transcription and translation of the recombinant heavy chain gene, while reduced cellular biomass synthesis surprisingly didn't significantly impact antibody production rates.
  • The research highlights the importance of using predictive modeling to guide engineering efforts aimed at enhancing protein production in mammalian cells, showing that productivity control varies by protein and cell line.
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Article Synopsis
  • This study investigates how different CHO cell lines control the production of recombinant human IgG(4) monoclonal antibodies, revealing a wide variation in production rates.
  • All cell lines produced more light chain mRNA and polypeptide compared to heavy chain due to faster transcription and improved stability, but they varied in translation rates and overall antibody assembly and secretion.
  • Findings suggest that optimizing monoclonal antibody production requires targeted cell engineering based on the specific capabilities of each cell line.
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Myocardial contusion is a complication of blunt thoracic injuries. Transthoracic echocardiography and electrocardiography (ECG) monitoring are important in suspected cases. We report a 54-year-old man, who sustained a number of injuries including blunt chest injury as a consequence of a road traffic accident.

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Objective: Prospective randomised study comparing patients with atrial fibrillation (AF) of more than 6 months duration after mitral valve surgery plus biatrial modified radiofrequency Maze procedure using Medtronic Cardioblate System (Cardioblate group, n=24) vs mitral valve surgery plus intensive rhythm control strategy (control group, n=25).

Methods: Patients were blinded to randomisation. Preoperatively, at discharge, and at 3-month and 1-year follow-up, echocardiography, quality of life assessments and ECGs were done.

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The increasing demand for recombinant therapeutic proteins has placed significant pressure on the biopharmaceutical industry to develop high-yielding, mammalian cell-based production systems. Current efforts to increase the production of recombinant proteins by mammalian host cells largely proceed by the lengthy screening of clonal derivatives rather than by directed genetic or metabolic engineering. However, the advent of systems biology has created a new set of tools that will ensure that future engineering strategies will be informed by an understanding of the genetic/regulatory and metabolic networks that determine the functional competence of mammalian cell factories in vitro.

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Many patients with potentially life-threatening cardiac conditions presenting with transient loss of consciousness are referred first to neurology clinics. Therefore, neurologists must remain competent to interpret electrocardiograms (ECGs) and in particular be able to identify those rare conditions that predict sudden cardiac death. A 12-lead ECG is cheap and readily available, and can give essential diagnostic information.

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Patients with syncope are usually referred to either neurology or cardiology clinics, yet the facilities for detailed syncope investigation are mostly in cardiac units. The diagnosis rests principally upon the history, but investigations may be required to support the clinical diagnosis. Close collaboration between the epilepsy clinician and a cardiologist is essential for effective investigation and safe management of syncope.

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